1.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
2.Investigation of the molecular mechanisms by which lncRNA MEG8 mediate the development of chronic obstructive pulmonary disease by regulating miR-367-3p/PTEN
Yi WANG ; Cheng CHENG ; Fei HUANG ; Guoqiang TONG
International Journal of Laboratory Medicine 2024;45(13):1595-1601
Objective Explore the molecular mechanism by which long chain non-coding(lncRNA)MEG8 regulates the development of chronic obstructive pulmonary disease(COPD)mediated by miR-367-3p/phos-phatase and tensin homolog(PTEN).Methods Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the expression level of lncRNA MEG8 in 16HBE cells and clinical tissues of chron-ic obstructive pulmonary disease(COPD).MEG8 was overexpressed in 16HBE cells stimulated by cigarette smoke extract(CSE),and MEG8 or PTEN were simultaneously knocked down after the addition of miR-367-3p inhibitor,then MTT assay,flow cytometry,enzyme-linked immunosorbent assay,and immunoblotting were used to detect changes in cell apoptosis,proliferation,and levels of inflammatory factors.The targeting rela-tionships of MEG8,miR-367-3p,and PTEN was verified by using the dual luciferase reporting system.Results MEG8 expression was reduced in CSE stimulated 16HBE cells and COPD clinical tissue samples(P<0.05).Compared to the CSE group,overexpression of MEG8 stimulated apoptosis and inflammatory fac-tor interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αlevels decreased(P<0.05)in 16HBE cells stimulated by CSE.The expression levels of proapoptotic proteins Bax,Caspase3,and Cleared caspase3 de-creased(P<0.05),and the expression level of apoptosis inhibitory factor Bcl-2 increased(P<0.05).The double luciferase Reporter gene experiment verified that MEG8 can target to inhibit miR-367-3p(P<0.05),and miR-367-3p can target to inhibit the expression of PTEN(P<0.05),thereby inhibiting the apoptosis and inflammatory response of 16HBE cells stimulated by CSE(P<0.05).Under CSE stimulation,compared to the Control group,the addition of miR-367-3p inhibitor significantly upregulated the protein expression level of PTEN in 16HBE cells(P<0.05),enhanced cell proliferation activity(P<0.05),reduced cell apoptosis(P<0.05),significantly downregulated the expression levels of proapoptotic proteins Bax,Caspase 3,and Cleared caspase 3(P<0.05),upregulated the expression level of anti apoptotic protein Bcl-2(P<0.05),and suppressed the inflammatory factor IL-1 β,IL-6 and TNF-α Knocking down MEG8 or PTEN can restore the protein expression level of PTEN(P<0.05),inhibit cell proliferation activity(P<0.05),reverse cell apoptosis caused by miR-367-3p inhibitor(P<0.05),and regulate apoptosis related proteins(P<0.05),and enhance the in-flammatory factor IL-1 β,IL-6 and TNF-α The level of(P<0.05).Conclusion MEG8 inhibits the apoptosis and inflammatory response of 16HBE cells stimulated by CSE by regulating miR-367-3p/PTEN molecular ax-is,and may provide a potential molecular target for the treatment of COPD.
3.Protective effect of dexmedetomidine on myocardial ischemia-reperfusion mice
Zhen-Fei HU ; Yi-Dan HUANG ; Xiao-Wen DAI
The Chinese Journal of Clinical Pharmacology 2024;40(4):574-578
Objective To investigate the protective effect of dexmedetomidine(Dex)pretreatment on myocardial ischemia-reperfusion mice and the effect of Nod-like receptor protein 3(NLRP3)inflammatory signaling pathway.Methods C57BL/6J mice were randomly divided into sham group(only threading without ligation),model group(recovery after ligation of left anterior descending coronary artery),positive group(modeling after intraperitoneal injection of 1 mg·kg-1 trimetazidine),Dex group(modeling after intraperitoneal injection of 20 μg·kg-1 dexmedetomidine),MCC950 group(modeling after intraperitoneal injection of 10 mg·kg-1 NLRP3 inhibitor MCC950),12 mice in each group.Cardiac function indexes were detected at 24 h after reperfusion,the expression level of related proteins in myocardial tissue was detected by Western blot,enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of serum factor,myocardial antioxidant index was detected by kit method,and apoptosis was detected by Tunel method.Results The NLRP3 protein expression levels of sham group,model group,positive group,Dex group and MCC950 group were 0.31±0.05,1.06±0.07,0.52±0.05,0.65±0.07 and 0.39±0.04,respectively;the expression levels of apoptosis-associated granuloid protein(ASC)were 0.27±0.08,0.88±0.09,0.46±0.05,0.59±0.07 and 0.34±0.04,respectively;CK-MB levels were(25.64±2.94),(102.08±7.04),(49.61±7.70),(60.86±5.24)and(63.24±5.38)U·L-1,respectively;IL-6 levels were(104.78±10.73),(231.54±15.56),(158.20±16.54),(165.10±14.77)and(141.17±14.08)pg·mL-1,respectively;Tunel positive cell rates were(4.34±0.16)%,(25.98±1.58)%,(8.74±0.93)%,(11.06±1.07)%and(9.19±0.88)%,respectively.Sham group were compared with model group;Dex group and MCC950 group were compared with model group,the above indexes were statistically significant(all P<0.05).Conclusion Dexmedetomidine preconditioning may prevent ischemia-reperfusion myocardial injury by inhibiting NLRP3/ASC/caspase-1 inflammatory pathway,inflammatory response and myocardial cell apoptosis.
4.Effects of hesperidin in promoting acute skin wound healing
Yi-Ming HUANG ; Fei-Fei CHEN ; Rong-Rong ZHANG ; Guang-Hui ZHU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2093-2097
Objective To study the effects of hesperidin on the migration ability of human keratinocytes(HaCaT)and human skin fibroblasts(HSF).Additionally,this research aims to preliminary investigate the influence and underlying mechanism of Hesperidin in facilitating the healing process of acute skin wounds in mice.Methods HaCaT and HSF were divided into blank group(without any treatment),control group(added 0.1%dimethyl sulfoxide)and experimental group(added 5.0 μg·mL-1 hesperidin)for 48 h.The healing ability of cells in vitro was detected by scratch test.The migration of cells was detected by Transwell migration test.C57 mice were randomly divided into model group,experimental-L,-H groups.The acute full-thickness skin defect wound model was established by surgical clipping of the full-thickness skin of the back of mice.The model group was given 0.5%dimethyl sulfoxide,and the experimental-L,-H groups were given 10,50 mg·kg-1 hesperidin solution,respectively.The protein expressions levels of β-catenin,proliferating cell nuclear antigen(PCNA),keratin 14 and collagen Ⅰ were detected by Western blot.Results The scratch healing rates of HaCaT-blank group,HaCaT-control group and HaCaT-experimental group were(21.05±1.10)%,(22.33±1.72)%and(41.61±2.90)%;the cell migration numbers were 57.00±11.36,60.38±10.11 and 287.75±20.21,respectively.The scratch healing rates of HSF-blank group,HSF-control group and HSF-experimental group were(17.82±1.62)%,(19.81±3.87)%and(64.22±1.94)%,the cell migration numbers were 43.25±7.98,40.75±6.70 and 140.88±14.35,respectively.The HaCaT-experimental group was compared with HaCaT-blank group and HaCaT-control group,and the HSF-experimental group was compared with HSF-blank group and HSF-control group,the differences were statistically significant(all P<0.05).The protein expression levels of β-catenin in the model group,experimental-L,-H groups were 0.53±0.06,0.74±0.17 and 1.44±0.11;the protein expression levels of keratin 14 were 0.33±0.06,0.54±0.07 and 1.26±0.16;the protein expression levels of PCNA were 0.46±0.05,0.72±0.09 and 1.14±0.11;the protein levels of collagen Ⅰ were 0.52±0.03,0.77±0.05 and 1.28±0.13,respectively.There were significant differences in the above indexes between the experimental-L,-H groups and the model group(P<0.05,P<0.01).Conclusion Hesperidin may promote the healing of acute skin wounds in mice by activating the Wnt/β-catenin signaling pathway and increasing the migration of HaCaT and HSF.
5.Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns
Qimin MA ; Wenbin TANG ; Xiaojian LI ; Fei CHANG ; Xi YIN ; Zhaohong CHEN ; Guohua WU ; Chengde XIA ; Xiaoliang LI ; Deyun WANG ; Zhigang CHU ; Yi ZHANG ; Lei WANG ; Choulang WU ; Yalin TONG ; Pei CUI ; Guanghua GUO ; Zhihao ZHU ; Shengyu HUANG ; Liu CHANG ; Rui LIU ; Yongji LIU ; Yusong WANG ; Xiaobin LIU ; Tuo SHEN ; Feng ZHU
Chinese Journal of Burns 2024;40(3):249-257
Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.
6.Correlation between salivary cystatin D level and salivary gland injury in patients with primary Sj?gren syndrome
Jing WANG ; Fei LI ; Yi HUANG ; Lingfei MO ; Hanchao LI ; Ying PAN ; Xiuyuan FENG ; Xinyi LIU ; Yuanyuan LI
Journal of Army Medical University 2024;46(21):2451-2456
Objective To investigate the correlation between salivary cystatin D level and salivary gland injury in patients with primary Sj?gren syndrome(pSS).Methods A total of 51 pSS patients admitted in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Xi'an Jiaotong University from September 1,2022 to June 30,2023,and 51 age-and gender-matched healthy individuals who took physical examination in the hospital during same period were enrolled in the study.The level of salivary cystatin D was detected,and the difference in the level between the 2 groups was compared using an independent-samples t test.Pearson correlation analysis was applied to analyze the correlation between salivary cystatin D and clinical parameters in the patients.Results The pSS patients had significantly lower cystatin D level than the healthy controls(206.55±108.11 vs 374.32±172.24 pg/mL,P<0.01).The cystatin D level in the pSS patients was positively correlated with both static(r=0.433,P=0.002)and dynamic salivary flow rates(r=0.363,P=0.009).The patients with higher score of salivary gland ultrasonography(SGUS)had obviously lower cystatin D than those with lower SGUS score(parotid gland:160.75±85.56 vs 290.53±95.17 pg/mL,P<0.01;submandibular gland:157.76±87.59 vs 276.25±97.06 pg/mL,P<0.01).The cystatin D level was also negatively correlated with peripheral blood IL-6 level(r=-0.453,P=0.001)and CD4+T cell count(r=-0.396,P=0.005)in the pSS patients.Conclusion Salivary cystatin D level can be used as an indicator of salivary gland damage for pSS patients.
7.Study on the clinical effect of meridian massage in the treatment of lumbar disc herniation
Sheng-Hua HE ; Huang-Sheng TAN ; Yong HUANG ; Hua-Long FENG ; Zhi-Ming LAN ; Yuan-Fei FU ; Yong JIANG ; Ju-Yi LAI
China Journal of Orthopaedics and Traumatology 2024;37(10):991-996
Objective To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH).Methods Between July 2020 and April 2023,82 patients with lumbar disc herniation were selected,including 58 males and 24 females,aged from 23 to 55 years old with an average of(43.76±6.64)years old.According to the different treatment methods,they were divided into observation group and control group with 41 cases in each group.The control group was treated with routine treatment,and the observation group was treated with meridian massage on the basis of routine treatment.In the control group,there were 30 males and 11 females;aged from 22 to 52 years old with an average of(42.27±9.34)years old;the Body mass index(BMI)ranged from 19 to 28 kg·m-2 with an average of(23.82±1.08)kg·m-2;the course of disease ranged from 0.5 to 3.0 years(2.40±0.48)years.There were 28 cases in L4,5 segment and 13 cases in L5S1 segment.In the observation group,there were 28 males and 13 females;the age ranged from 19 to 54 years old(42.19±9.26)years old;the BMI ranged from 18 to 29 kg·m-2 with an average of(23.73±1.15)kg·m-2;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45)years;there were 26 cases in L4,5 segment and 15 cases in L5S1 segment.Visual analogue scale(VAS),Oswestry disability index(ODI),M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment,and the clinical efficacy was evaluated by the standard of curative effect evaluation.Results After treatment,VAS[(3.24±1.45)vs(4.46±0.64)],ODI[(11.45±1.98)%vs(17.21±2.74)%]and TCM symptom score[(2.03±0.27)vs(3.99±0.54)]of the observation group were lower than those of the control group.The score of M-JOA[(23.43±2.61)vs(19.37±1.62)]increased(P<0.05).The scores of VAS,ODI andTCM symptoms in the observation group were lower than those in the control group,while the scores of M-JOA were higher than those in the control group(P<0.05).Conclusion Meridian massage is effective in the treatment of LDH,which can effectivelyrelieve low back pain,improve clinical symptoms and increaselumbar function,which is worthy of clinical promotion.
8.MTHFD2 Is a Negative Regulatory Molecule for the Formation of Heterotypic Cell-in-Cell Structures
Peng-Fei FENG ; Chen-Yu LIU ; Yi-Nuo HUANG ; Zhuo-Ran SUN ; Yang-Yi ZHANG ; Hong-Yan HUANG ; Chen-Xi WANG ; Xiao-Ning WANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(6):819-826
Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P<0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P<0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.
9.Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma
Ning WANG ; Fei-Li CHEN ; Yi-Lan HUANG ; Xin-Miao JIANG ; Xiao-Juan WEI ; Si-Chu LIU ; Yan TENG ; Lu PAN ; Ling HUANG ; Han-Guo GUO ; Zhan-Li LIANG ; Wen-Yu LI
Journal of Experimental Hematology 2024;32(5):1420-1426
Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01%and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3%and 61%,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.
10.Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients
Jia-Qian XU ; Juan WANG ; Su-Ying LU ; Yan-Peng WU ; Lan-Ying GUO ; Bo-Yun SHI ; Fei-Fei SUN ; Jun-Ting HUANG ; Jia ZHU ; Zi-Jun ZHEN ; Xiao-Fei SUN ; Yi-Zhuo ZHANG
Journal of Experimental Hematology 2024;32(6):1733-1737
Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

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