OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child ; Humans ; DNA-Binding Proteins/genetics* ; Gene Frequency ; Genotype ; Methotrexate ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Transcription Factors/genetics* ; Drug Resistance, Neoplasm

Objective: To evaluate the efficacy and safety of Beijing Children's Hospital (BCH) modified hemophagocytic lymphohistiocytosis (HLH) 04 regimen in the treatment of childhood HLH. Methods: A retrospective cohort study was conducted. From January 2016 to December 2017, 110 children with HLH who were treated with the modified HLH-04 regimen (replacing dexamethasone with methylprednisolone during the induction period, reducing the dose and frequency of etoposide, and not using cyclosporine except for autoimmune-related HLH) at the Hematology Oncology Center of Beijing Children's Hospital were selected as the modified group, while 102 children treated with the standard HLH-04 regimen from January 2012 to December 2015 were selected as the control group. The early remission rate, survival rate and adverse reactions of two groups were compared. Rank sum test and chi square test were used for comparison between groups. Results: The age of onset in the modified group was 1.9 (1.1, 3.5) years, with 65 males and 45 females. The age of onset in the control group was 2.0 (1.2, 4.6) years, with 47 males and 55 females. No significant difference was found in age and gender between 2 groups (both P>0.05). Except for fibrinogen (1.3 (1.0, 1.7) vs. 1.1 (0.8, 1.4) g/L, Z=-2.67, P=0.008) and natural killer cell activity (13.9 (13.4, 16.3) % vs.14.9 (12.0, 16.1) %, Z=-2.34, P=0.028), there were no statistically significant differences in etiology, disease duration, first clinical presentation, or laboratory tests between 2 groups (all P>0.05). At 2 months and 3 years, there were no statistically significant differences in overall survival between 2 groups (84.5% (93/110) vs.76.5% (78/102), 78.2% (86/110) vs. 67.6% (69/102), χ²=2.28, 3.07, P=0.131, 0.080). The first 3 weeks were the most common time for bone marrow suppression in the modified group, with a lower incidence than in the control group (47.3% (52/110) vs. 62.7% (64/102), χ²=5.11, P=0.024). The modified group had a lower rate of fungal infections than the control group (3.6% (4/110) vs. 13.7% (14/102), χ²=6.93, P=0.008). Compared with the control group, fewer children in the modified group died as a result of side effects from chemotherapy (8.0% (2/25) vs.30.3% (10/33), χ²=4.31, P=0.038). Conclusion: The BCH modified HLH-04 regimen reduced the intensity of chemotherapy, with overall efficacy no worse than the standard HLH-04 regimen, and significantly reduced the rate of chemotherapy-related myelosuppression, fungal infection and mortality.
Child ; Cyclosporine/therapeutic use* ; Etoposide ; Female ; Hospitals ; Humans ; Lymphohistiocytosis, Hemophagocytic/etiology* ; Male ; Retrospective Studies

Objective To determine the levels and significance of Krebs von den lungen-6(KL-6), pulmonary surfactant protein A (SP-A), SP-D and interleukin (IL)-6 in patients with connective tissue disease interstitial lung disease (CTD-ILD). Methods The serum KL-6, SP-A, SP-D and IL-6 in all subjects were detected and the imaging and pulmonary function were recorded t test, χ2 test, non-parametric test, ANOVA and correlation analysis were used for data analysis. Results ① The levels of serum KL-6, SP-A, SP-D, IL-6 in the CTD-ILD group [551.4 (428.2, 883.5) U/ml, 938.4(435.2, 2324.7) pg/ml, 90.7 (80.7, 100.3) ng/ml and 30.4 (22.9, 41.7) pg/ml; P all<0.05] was significantly higher than that in the CTD group [192.9 (139.2, 266.2) U/ml; 458.0 (372.6, 529.0) pg/ml; 80.0 (71.2, 98.3) ng/ml; 18.6 (4.9, 31.0) pg/ml, Z=-5.383, -3.76, -2.123,-3.903, P all <0.05]; and higher than healthy controls (n=30) [183.2(141.9, 216.6) U/ml; 229.0(162.0, 248.0) pg/ml;50.8(26.1, 96.4) ng/ml;7.1(3.7, 8.7) pg/ml, Z=-5.801,-8.13, 2.272, 3.266;P all<0.05].②The levels of KL-6 in pulmonary HRCT for active ILD group was significantly higher than the non-active ILD group [998.5 (640.3, 1293.3) U/ml vs 565.0(434.0, 799.5) U/ml, Z=2.182, P=0.023], there was no statistical difference in the levels of SP-A, SP-D, IL-6 between the 2 groups. ③ Spearman correlation analysis showed that KL-6 was negatively correlated with forced vital capacity (FVC%);SP-D, IL-6 and diffusing capacity of carbon monoxide (DLCO %). ④ Logistic multiple regression analysis showed that KL-6 [OR=1.017, P=0.002, 95%CI (1.006, 1.028)], SP-A [OR=1.023, P=0.009, 95%CI (1.006, 1.041)], SP-D [OR=1.175, P=0.009, 95%CI (1.075, 1.264)], IL-6[OR=1.213, P=0.001, 95%CI(1.088, 1.354)] were the risk factors for ILD. Conclusion Serum KL-6, SP-A, SP-D and IL-6 are significantly increased and correlate with CTD-ILD. KL-6 is related to the pulmonary inflammatory disease and vital capacity, while SP-D and IL-6 are related to diffusion function.

In order to find out the composition, characteristics and traditional utilization characteristics of Dai medicine and promote the rational protection, inheritance and utilization of the resources and traditional knowledge of Dai medicine in China, the resources of traditional Dai medicine have been investigated systematically and the traditional knowledge of Dai medicine have been analyzed in the article. We found out that there were altogether 1 077 kinds of traditional Dai medicine in China and among which 272 were the first time recorded in the condition of Dai folk medical uses. There were 1 053 plant medicines which belong to 169 family and 694 genus. These plant medicines mainly distributed in the southern, west southern and east southern area of Yunnan province, the southern area of Guangxi, Guangdong, Guizhou, Sichuan, Fujian province and tropical, subtropical district as Taiwan, and more than 94.49% plant medicines could be found in Yunnan province. From the point of plant life form, they were major herbaceous or shrubby plants; When it is used as medicinal part, root and rhizome of plants account for the highest proportion, the next were whole plant and leaves. From nature, flavor and channel tropism points of view, the largest proportion of Dai medicines were cool, bitter-tasted and possesses water element. In terms of treatment of disease types, most of the drugs can treat gastrointestinal diseases, next were drugs that could be used to treat upper respiratory infection, traumatological and rheumatic diseases, urinary infection, gynecological diseases, hepatopathy, puerperium fever and diseases caused by poisonous insects and beast of prey bite. The study revealed that the resources of traditional Dai medicine and traditional knowledge of application were abundant in China, but the resources of traditional Dai medicine and traditional knowledge of application were faced with the risk of gradually reduce and loss. The article suggested that we should take measures to strengthen the study of protection and utilization of important traditional Dai medicine and endangered resources along with the protection and transmission of traditional knowledge of Dai nationalistic medicine.

OBJECTIVETo evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.

METHODSixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.

RESULT(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.

CONCLUSIONIntermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.

Body Height ; drug effects ; Bone Development ; Child ; Child Development ; drug effects ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; therapeutic use ; Growth Disorders ; drug therapy ; Human Growth Hormone ; administration & dosage ; therapeutic use ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology ; Stanozolol ; administration & dosage ; therapeutic use ; Treatment Outcome

Objective To construct the eukaryotic expression vector PCI-dhfr-λ1 and PCI-dhfrSP163-λ1 which linked the enhancer SP163 with interferon λ1.Then express the interferon λ1 in CHO (dhfr-) cells.Methods Using PCR method to introduce the restriction enzyme sites and through the fusion PCR binding the enhancer with the interferon λ1.After sequenced,λ1 and SP163-λ1 was inserted into PCI-dhfr forming the expression vector PCI-dhfr-λ1 and PCI-dhfr-SP163-λ1 which was constructed successfully confirming by sequencing.Then the expressing vectors were transfected into CHO(dhfr-) cells using liposome transfection method and interferon λ1 protein was assayed with indirect immunofluorescence and Western Blot.Using cytopathic effect inhibition evaluated the antiviral activity of interferon λ1.Results Successfully constructing the eukaryotic expression vectors of interferon λ1 and the vectors could express interferon λ1.The result of immunofluorescence showed the enhancer developed the expression of interferon λ1.Detecting the interferon λ1 in CHO (dhfr-) cells after transfecting 48 hour using Western Blot.The cytopathic effect inhibition showed the expressed interferon λ1 has the antiviral activity.Conclusion Successfully expressed the interferon λ1 in CHO(dhfr-) cells and the protein possesses antiviral activity,which may supply a valuable basis for building the stable cell line of interferon λ1.

This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its possible mechanism. The animal model with allo-HSCT aGVHD was established by using purebred mice (male mouse C57BL/6 as donor, female mouse BALB/c as recipient) with complete-unidentical major histocompatibility antigen. The recipient mice were randomly divided into 3 groups: group 1 in which mice were injected with high purity (95%) flagellin before and after allo-HSCT respectively, group 2 in which mice received allo-HSCT without injection of flagellin, group 3 in which mice were radiated alone. The aGVHD features of mice in group 1 and 2 were observed and compared. The results showed that the typical symptoms of aGVHD appeared in transplanted mice. The death peak of mice in group 2 appeared at day 4-5 after transplantation. The aGVHD symptoms were obviously alleviated and the mean survival time was prolonged significantly in mice group 1 as compared with mice in group 2 (P < 0.05). The comparison of WBC count in peripheral blood of mice in 3 groups before transplantation showed no significant difference (P > 0.05), while WBC count of mice in group 1 and 2 showed the significant difference at days 14 and 21 after transplantation (P < 0.05). The pathological appearances of aGVHD in mice of group 1 were obviously reduced as compared with mice in group 2. The flow cytometric detection of Treg cell/CD4(+) T cell levels at different time before and after transplantation demonstrated that the Treg cell level in mice of group 1 at weeks 2-4 after transplantation significantly increased as compared with mice in group 2 (P < 0.05). It is concluded that flagellin can effectively prevent the aGVHD occurrence after allo-HSCT, reduce the symptoms and pathological changes of aGVHD, obviously prolong mean survival time of mice in group 1. The mechanism of flagellin effect may be associated to increase of Treg cell level in mice after allo-HSCT.
Animals ; Female ; Flagellin ; therapeutic use ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; Toll-Like Receptor 6 ; agonists ; Transplantation, Homologous

Objective To express and purify HBoV VP2 protein,and the monoclonal antibody against HBoV VP2 protein was prepared with hybridoma technique.Methods The HBoV VP2 cloned into vector pET-30a was expressed in E.coil.After purified by immobilized metal affinity chromatography,the BALB/c mouse was immunized with purified protein as antigen.The positive hybridoma cells were screened with hybridoma technique and ELISA assay. Isotype and titer of the monoclonal antibody were detected.Results The recombinant HBoV VP2 protein was expressed and purified,and then the monoclonal antibody was obtained with hybridoma technique.The titer of the IgG monoclonal antibody was up to 1 ∶ 4 × 105.Conclusion Monoclonal antibody against recombinant HBoV VP2 protein was prepared and the antibody titer was high.This work may provide a new method in rapid diagnosis and study of HBoV.

Objective To analyze the community in dental plaque of elder people with root caries.Methods Total DNAs were extracted from the root caries dental plaques of nine elders over 60 years of age.Polymerase chaid reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the microbial composition,DGGE bands were excised from the gels for sequencing and identification.Results The dominant genus in root caries dental plaque of elder people were:Acinetobacte [0.9％ (1/114) ],Actinobaculum [ 1.8％ ( 2/114 ) ],Actinomyces [ 15.8％ ( 18/114 ) ],Aggregatibacter [0.9％ (1/114) ],Capnocytophaga [ 14.0％ ( 16/114 ) ],Corynebacterium [ 0.9％ ( 1/114 ) ],Haemophilus [0.9％ ( 1/1 14 ) ],Mobiluncus [ 0.9％ ( 1/114 ) ],Naxibacter [ 0.9％ ( 1/1 14 ) ],Neisseriaceae [ 10.5％ (12/114) ],Porphyromonas [ 0.9％ ( 1/114 ) ],Prevotella [ 12.3％ ( 14/114 ) ],Selenomonas [ 6.1％(7/114 ) ],Staphylococcus [ 1.8％ ( 2/114 ) ],Oralis streptococcus [ 6.1％ ( 7/114 ) ],Mutans streptococcu [7.9％ (9/114) ],Tannerella [0.9％ ( 1/114)],Treponema [ 1.8％ (2/114)],Veillonella [ 10.5％(12/114) ] and two uncultured unknown genus [ 1.8％ (2/114 )].Uncultred genotypes accounted for 19.30％ of the total.Gram-positive bacteria genotype accounted for 31.6％ (36/114),and Gram-negative bacteria genotype accounted for 66.7％ (76/114).Conclusions There were many bacteria genotypes in root caries dental plaque in the elderly,which were widely distributed.Gram-negative bacteria accounted for the majority.Genotype-specific pathogenic bacteria were not found.

Objective To investigate the situation of normal blood pressure and prevalence and risk factors of prehypertension in Han, Uygur and Hazakh population ≥35 years old of Xinjiang Uygur autonomous region.Methods Random samples were used to analyze the incidence of normal blood pressure and prehypertension in 3 nationalities based on data from Han, Uygur and Hazakh residents living in 7 areas (Urumqi,Ke lamayi, Fukang, the Turfan Basin locality, Hetian locality, Altay locality,and Yili Hazakh autonomous prefecture) in Xinjiang Uygur autonomous region.Results A total of 16 460 subjects were selected with cluster sampling, and eligible data of 14 618 subjects were actually analyzed in Han, Uygur and Hazakh population ≥35 years old of Xinjiang Uygur autonomous region.Incidence of normal blood pressure was 24.9% and the prevalence of prehypertension was 34.24% (35.6% fro male and 31.5% for female, P<0.01) in Han, Uygur and Hazakh population ≥35 years old in Xinjiang Uygur autonomous region.The prevalence of prehypertension was 37.34%, 32.95% and 30.62% in Han, Uygur and Hazakh population, respectively. The prevalence of prehypertension decreased with increasing age in Han and Uygur population ≥45 years old, and in Hazakh population≥35 years old (all P<0.05).Multiple logistic regression analysis revealed that hypertriglyceridemia≥1.7 mmol/L, age≥45 years old, fasting plasma glucose≥7.0 mmol/L and body mass index≥24.0 kg/m2 were risk factors while the female was a protective factor of prehypertension. Conclusion The people with normal blood pressure is few and the prevalence of prehypertension is high in Han, Uygur and Hazakh population ≥35 years old of Xinjiang Uygur autonomous region, and it is associated with many risk factors.