2.A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia.
Yong-Li HUA ; Qi MA ; Zi-Wen YUAN ; Xiao-Song ZHANG ; Wan-Ling YAO ; Peng JI ; Jun-Jie HU ; Yan-Ming WEI
Chinese Journal of Natural Medicines (English Ed.) 2019;17(4):275-290
		                        		
		                        			
		                        			Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.
		                        		
		                        		
		                        		
		                        			Anemia
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Chromatography, Liquid
		                        			;
		                        		
		                        			Cyclophosphamide
		                        			;
		                        		
		                        			toxicity
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Metabolic Networks and Pathways
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Metabolome
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Metabolomics
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Tandem Mass Spectrometry
		                        			
		                        		
		                        	
3.Efficacy and safety evaluation of gemcitabine combined with ifosfamide in patients with advanced nasopharyngeal carcinoma after failure of platinum-based chemotherapy.
Shaoxuan HU ; Xiaohui HE ; Email: XIAOHUIH2008@163.COM. ; Mei DONG ; Bo JIA ; Shengyu ZHOU ; Jianliang YANG ; Sheng YANG ; Changgong ZHANG ; Peng LIU ; Yan QIN ; Lin GUI
Chinese Journal of Oncology 2015;37(8):632-636
OBJECTIVETo evaluate the efficacy and safety of gemcitabine combined with ifosfamide (GI regimen)in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy.
METHODSThe clinical data of 27 nasopharyngeal carcinoma patients, who received GI regimen between April 2005 and March 2014 after failure of prior platinum-based chemotherapy, were retrospectively reviewed,and relevant prognostic factors were explored.
RESULTSAll patients were evaluable for efficacy and toxicity. No patient achieved complete response (CR). Partial response (PR) was achieved in ten patients, stable disease (SD) in thirteen patients, progressive disease (PD) in four patients, with a response rate of 37.0% and an overall disease control rate (PR+SD) of 85.2%. For ten PR patients, the median duration of response was 5.5 months. The median progression-free survival of the whole group was 6.7 months, and the Kaplan-Meier estimate of median overall survival was 17.4 months. The 1-year survival rate was 72.6%. Toxicity was mainly hematological: Grade III or IV anemia, neutropenia and thrombocytopenia were found in 3.7%, 37.0% and 18.5% of all patients, respectively. Univariate and multivariate analyses indicated that dose intensity of gemcitabine was a significant prognostic factor for PFS, whereas salvage treatment after failure of GI regimen was a significant prognostic factor for OS.
CONCLUSIONSGemcitabine and ifosfamide combination is effective and well tolerated by patients with advanced nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Further clinical study is warranted.
Anemia ; chemically induced ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease-Free Survival ; Humans ; Ifosfamide ; administration & dosage ; adverse effects ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Nasopharyngeal Neoplasms ; drug therapy ; mortality ; pathology ; Neutropenia ; chemically induced ; Platinum ; therapeutic use ; Remission Induction ; Salvage Therapy ; Survival Rate ; Thrombocytopenia ; chemically induced ; Treatment Failure
4.Analysis of postoperative chemotherapy-related anemia in elderly cancer patients.
Su HE ; Zhang LINGYUN ; Liu YUNPENG
Chinese Journal of Oncology 2015;37(4):290-292
OBJECTIVEThis study was conducted to investigate the correlation between anemia and postoperative chemotherapy in elderly cancer patients.
METHODSOne hundred and fifty-seven elderly patients ( age ≥ 60) with pathologically confirmed breast, lung and digestive tract cancers, who had HGB ≥ 120 g/L and ECOG scores 0-2, were included in this study. We reviewed their clinicopathological data and analyzed the correlation of anemia in breast cancer patients after 1, 3 or 5 cycles and lung cancer patients after 1, 2 or 3 cycles of postoperative chemotherapy.
RESULTSAmong the 157 cases, the overall proportion of anemia was 31.8% (50/157) , with 18.8% in male and 47.2% in female patients (P < 0.001). After three cycles of chemotherapy, the proportion of anemia was 57.9% in lung cancer, 34.5% in breast cancer, 26.3% in gastric cancer and 9.3% in colorectal cancer patients (P < 0.001). The proportion of anemia during 5 cycles chemotherapy (three cycles in lung cancer) was gradually increasing. In the lung cancer patients, anemia was observed in 66.7% of patients who received vinorelbine plus cispiatin regimen and 25.0% of cases who received vinorelbine regimen chemotherapy (P = 0.044).
CONCLUSIONSIn most elderly patients with normal hemoglobin level and in good conditions, the chemotherapy-related anemia is mild and less frequent. Age should not limit the adjuvant chemotherapy in elderly cancer patients. Attention should be paid to the possibility of anemia in elderly female lung cancer patients receiving multiple cycle platinum-based chemotherapy regimens.
Aged ; Anemia ; chemically induced ; epidemiology ; Antineoplastic Agents ; adverse effects ; Breast Neoplasms ; drug therapy ; Chemotherapy, Adjuvant ; Cisplatin ; adverse effects ; Colorectal Neoplasms ; drug therapy ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Stomach Neoplasms ; drug therapy ; Vinblastine ; adverse effects ; analogs & derivatives
5.Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy.
Jow Jyh HWANG ; Ching Chu LO ; Chien Hung LIN ; Hsu Sheng CHENG ; I Wen HUNG ; Wan Ju TSAI ; Chien Hui HUNG
Gut and Liver 2015;9(2):214-223
		                        		
		                        			
		                        			BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anemia/chemically induced/genetics
		                        			;
		                        		
		                        			Antiviral Agents/*adverse effects
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Drug Therapy, Combination/adverse effects
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hematologic Diseases/*chemically induced/genetics
		                        			;
		                        		
		                        			Hepacivirus
		                        			;
		                        		
		                        			Hepatitis C/*drug therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interferon-alpha/adverse effects
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			*Polymorphism, Single Nucleotide
		                        			;
		                        		
		                        			Pyrophosphatases/*genetics
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Ribavirin/adverse effects
		                        			;
		                        		
		                        			Taiwan
		                        			;
		                        		
		                        			Thrombocytopenia/chemically induced/genetics
		                        			
		                        		
		                        	
6.Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy.
Jow Jyh HWANG ; Ching Chu LO ; Chien Hung LIN ; Hsu Sheng CHENG ; I Wen HUNG ; Wan Ju TSAI ; Chien Hui HUNG
Gut and Liver 2015;9(2):214-223
		                        		
		                        			
		                        			BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anemia/chemically induced/genetics
		                        			;
		                        		
		                        			Antiviral Agents/*adverse effects
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Drug Therapy, Combination/adverse effects
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hematologic Diseases/*chemically induced/genetics
		                        			;
		                        		
		                        			Hepacivirus
		                        			;
		                        		
		                        			Hepatitis C/*drug therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interferon-alpha/adverse effects
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			*Polymorphism, Single Nucleotide
		                        			;
		                        		
		                        			Pyrophosphatases/*genetics
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Ribavirin/adverse effects
		                        			;
		                        		
		                        			Taiwan
		                        			;
		                        		
		                        			Thrombocytopenia/chemically induced/genetics
		                        			
		                        		
		                        	
7.Drug-induced immune haemolytic anaemia caused by levofloxacin.
Shashvat SUKHAL ; Shweta GUPTA
Singapore medical journal 2014;55(8):e136-8
		                        		
		                        			
		                        			Drug-induced immune haemolytic anaemia (DIIHA) is extremely rare. We herein report a case of life-threatening DIIHA due to levofloxacin. This is the second case reported in the literature. A 51-year-old woman presented with complaints of fatigue after 4-5 days of levofloxacin therapy for a lung infection. At presentation, she was found to have haemolysis with a positive Coombs test and IgG autoantibodies. Levofloxacin was identified as the probable culprit, using the Naranjo adverse drug reaction probability scale. Upon discontinuation of the drug and initiation of steroids, the patient's haematological parameters stabilised. Diagnosis of DIIHA is made through a history of intake of levofloxacin, clinical and laboratory features of haemolysis and a positive Coombs test. An autoantibody screen is most commonly positive for warm antibodies (IgG type). It is essential for clinicians to recognise this rare complication caused by a commonly prescribed medication, discontinue the offending drug and initiate treatment.
		                        		
		                        		
		                        		
		                        			Anemia, Hemolytic
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			Anti-Bacterial Agents
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Autoantibodies
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fluoroquinolones
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Hemolysis
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunoglobulin G
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Levofloxacin
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Steroids
		                        			;
		                        		
		                        			therapeutic use
		                        			
		                        		
		                        	
8.An Imported Case of Severe Falciparum Malaria with Prolonged Hemolytic Anemia Clinically Mimicking a Coinfection with Babesiosis.
Young Ju NA ; Jong Yil CHAI ; Bong Kwang JUNG ; Hyun Jung LEE ; Ji Young SONG ; Ji Hye JE ; Ji Hye SEO ; Sung Hun PARK ; Ji Seon CHOI ; Min Ja KIM
The Korean Journal of Parasitology 2014;52(6):667-672
		                        		
		                        			
		                        			While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.
		                        		
		                        		
		                        		
		                        			Anemia, Hemolytic/chemically induced/*etiology/*pathology
		                        			;
		                        		
		                        			Anti-Bacterial Agents/therapeutic use
		                        			;
		                        		
		                        			Antimalarials/therapeutic use
		                        			;
		                        		
		                        			Artemisinins/adverse effects/therapeutic use
		                        			;
		                        		
		                        			Atovaquone/therapeutic use
		                        			;
		                        		
		                        			Azithromycin/therapeutic use
		                        			;
		                        		
		                        			Babesiosis/complications/*diagnosis/drug therapy/*pathology
		                        			;
		                        		
		                        			Benin
		                        			;
		                        		
		                        			Blood/parasitology
		                        			;
		                        		
		                        			Coinfection/diagnosis/pathology
		                        			;
		                        		
		                        			Drug Combinations
		                        			;
		                        		
		                        			France
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Korea
		                        			;
		                        		
		                        			Malaria, Falciparum/complications/*diagnosis/drug therapy/*pathology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Plasmodium falciparum/*isolation & purification
		                        			;
		                        		
		                        			Proguanil/therapeutic use
		                        			;
		                        		
		                        			Travel
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
10.Successful treatment of paraquat poisoning with hemolytic anemia: a report of 1 case.
Bao-quan SUN ; Bo ZHAO ; Ping LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2013;31(8):624-624
		                        		
		                        		
		                        		
		                        			Anemia, Hemolytic
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			therapy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Paraquat
		                        			;
		                        		
		                        			poisoning
		                        			;
		                        		
		                        			Poisoning
		                        			;
		                        		
		                        			therapy
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
            
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