BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
Calf spleen extract(CSE) has been clinically used as an adjuvant agent in malignant tumor therapy.It can improve the physical status of patients.However,its mechanism of action remains relatively unclear.In this study...Calf spleen extract(CSE) has been clinically used as an adjuvant agent in malignant tumor therapy.It can improve the physical status of patients.However,its mechanism of action remains relatively unclear.In this study,we investigated the effect of CSE on leucopenia in mice and on promyelocytic leukemia cells(HL60).CSE in 10 mL/kg(2.5 mg bioactive polypeptides and 190μg ribose/mL) significantly increased leukocyte numbers in leucopenia mice.The effect on neutrophil numbers,among all leukocytes,was the most evident.CSE stimulated the proliferation of bone marrow cells in vitro and decreased the GM-CSF level in serum.In addition,CSE significantly reduced the viability of HL60 cells,decreased the production of lactate and adenosine triphosphate(ATP) of these cells.CSE induced the apoptosis and S-phase arrest in HL60 cells.In conclusion,CSE can enhance leukocyte numbers,which may be attributed to its direct stimulatory effect on bone marrow cells.CSE is an inhibitor of promyelocytic leukemia cell viability,which may be attributed to the induction of the apoptosis,the arrest of cell cycle and the inhibition of the glycolysis of cells.展开更多
Calf spleen extract （CSE） has been clinically used as an adjuvant agent in malignant tumor therapy. It can improve the physical status of patients. However, its mechanism of action remains relatively unclear. In thi...Calf spleen extract （CSE） has been clinically used as an adjuvant agent in malignant tumor therapy. It can improve the physical status of patients. However, its mechanism of action remains relatively unclear. In this study, we investigated the effect of CSE on leucopenia in mice and on promyelocytic leukemia cells （HL60）. CSE in 10 mL/kg （2.5 mg bioactive polypeptides and 190 pg ribose/mL） significantly increased leukocyte numbers in leucopenia mice. The effect on neutrophil numbers, among all leukocytes, was the most evident. CSE stimulated the proliferation of bone marrow cells in vitro and decreased the GM-CSF level in serum. In addition, CSE significantly reduced the viability of HL60 cells, decreased the production of lactate and adenosine triphosphate （ATP） of these cells. CSE induced the apoptosis and S-phase arrest in HL60 cells. In conclusion, CSE can enhance leukocyte numbers, which may be attributed to its direct stimulatory effect on bone marrow cells. CSE is an inhibitor ofpromyelocytic leukemia cell viability, which may be attributed to the induction of the apoptosis, the arrest of cell cycle and the inhibition of the glycolysis of cells.展开更多
In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative m...In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative meta analysis is done for 4 studies of dichotomous data and 5 studies of continuous data. Both of them have positive results. Majority of these trials have methodological and/or reporting shortcomings. Overall, the existing evidence supports the value of acupuncture for the treatment of leucopenia induced by chemo or radio therapy. However, the evidence is still not fully convincing. There is an urgent need for well planned, large scale and multiple center studies to assess the effectiveness and cost effectiveness of acupuncture under real life conditions.展开更多
This article reports the effects ot pure Radix Astragali preparation (PAP) in treating 115 cas-es of leucopenia. These cases were divided at random into two groups. Group A (58 cases) was treated byhighly concentrated...This article reports the effects ot pure Radix Astragali preparation (PAP) in treating 115 cas-es of leucopenia. These cases were divided at random into two groups. Group A (58 cases) was treated byhighly concentrated PAP, every 10 ml equal to 15 grams of Radix Astragali (RA) , group B ( 57 cases) wastreated by lowly concentrated PAP, every 10 ml equal to 5 g of RA. The patients took the PAP twice a day,10 ml each time. The course of treatment was 8 weeks tor both groups. The results showed there was an ob-vious increase of the WBC counts in both groups after treatment ( P< 0. 001 ) . The effectiveness in group Awas 82 . 76% , while in group B 47. 37% , they were statistically different ( P< 0 . 01 ) . The total effective rateof tlie 2 groups was 65. 22% . According to the comparison average WBC counts after treatment of group Awas significantly higher than that of group B ( P < 0. 05) . The results were dose-dependent. The author holdsthat RA is an effective drug in treating leucopenia, and increasing the dosage could enhance its effectiveness.展开更多
基金Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
文摘Calf spleen extract(CSE) has been clinically used as an adjuvant agent in malignant tumor therapy.It can improve the physical status of patients.However,its mechanism of action remains relatively unclear.In this study,we investigated the effect of CSE on leucopenia in mice and on promyelocytic leukemia cells(HL60).CSE in 10 mL/kg(2.5 mg bioactive polypeptides and 190μg ribose/mL) significantly increased leukocyte numbers in leucopenia mice.The effect on neutrophil numbers,among all leukocytes,was the most evident.CSE stimulated the proliferation of bone marrow cells in vitro and decreased the GM-CSF level in serum.In addition,CSE significantly reduced the viability of HL60 cells,decreased the production of lactate and adenosine triphosphate(ATP) of these cells.CSE induced the apoptosis and S-phase arrest in HL60 cells.In conclusion,CSE can enhance leukocyte numbers,which may be attributed to its direct stimulatory effect on bone marrow cells.CSE is an inhibitor of promyelocytic leukemia cell viability,which may be attributed to the induction of the apoptosis,the arrest of cell cycle and the inhibition of the glycolysis of cells.
文摘Calf spleen extract （CSE） has been clinically used as an adjuvant agent in malignant tumor therapy. It can improve the physical status of patients. However, its mechanism of action remains relatively unclear. In this study, we investigated the effect of CSE on leucopenia in mice and on promyelocytic leukemia cells （HL60）. CSE in 10 mL/kg （2.5 mg bioactive polypeptides and 190 pg ribose/mL） significantly increased leukocyte numbers in leucopenia mice. The effect on neutrophil numbers, among all leukocytes, was the most evident. CSE stimulated the proliferation of bone marrow cells in vitro and decreased the GM-CSF level in serum. In addition, CSE significantly reduced the viability of HL60 cells, decreased the production of lactate and adenosine triphosphate （ATP） of these cells. CSE induced the apoptosis and S-phase arrest in HL60 cells. In conclusion, CSE can enhance leukocyte numbers, which may be attributed to its direct stimulatory effect on bone marrow cells. CSE is an inhibitor ofpromyelocytic leukemia cell viability, which may be attributed to the induction of the apoptosis, the arrest of cell cycle and the inhibition of the glycolysis of cells.
文摘In the present paper, the authors analyze the academic theses of acupuncture for treatment of leucopenia induced by chemo or radio therapy. A total of 14 theses are retrieved and all written in Chinese. Quantitative meta analysis is done for 4 studies of dichotomous data and 5 studies of continuous data. Both of them have positive results. Majority of these trials have methodological and/or reporting shortcomings. Overall, the existing evidence supports the value of acupuncture for the treatment of leucopenia induced by chemo or radio therapy. However, the evidence is still not fully convincing. There is an urgent need for well planned, large scale and multiple center studies to assess the effectiveness and cost effectiveness of acupuncture under real life conditions.
文摘This article reports the effects ot pure Radix Astragali preparation (PAP) in treating 115 cas-es of leucopenia. These cases were divided at random into two groups. Group A (58 cases) was treated byhighly concentrated PAP, every 10 ml equal to 15 grams of Radix Astragali (RA) , group B ( 57 cases) wastreated by lowly concentrated PAP, every 10 ml equal to 5 g of RA. The patients took the PAP twice a day,10 ml each time. The course of treatment was 8 weeks tor both groups. The results showed there was an ob-vious increase of the WBC counts in both groups after treatment ( P< 0. 001 ) . The effectiveness in group Awas 82 . 76% , while in group B 47. 37% , they were statistically different ( P< 0 . 01 ) . The total effective rateof tlie 2 groups was 65. 22% . According to the comparison average WBC counts after treatment of group Awas significantly higher than that of group B ( P < 0. 05) . The results were dose-dependent. The author holdsthat RA is an effective drug in treating leucopenia, and increasing the dosage could enhance its effectiveness.
