[Changes of insulin-like growth factor 1 axis in chronic kidney disease and its role in skeletal muscle atrophy].

Objective: To investigate the changes of insulin-like growth factor 1 (IGF-1) axis in chronic kidney disease (CKD) and its role in skeletal muscle atrophy. Methods: A total of 240 patients with CKD stage 1-5 (without dialysis treatment) were included between August 2016 and February 2017. Serum IGF-1 and IGF-1 binding protein-3 (IGFBP-3) were measured using chemiluminescence, and the influencing factors of serum IGF-1 and IGFBP-3 were analyzed. Besides, male Sprague-Dawley rats (200-250 g) were randomly assigned to the sham-operated control group (Control, n=15) and the 5/6 nephrectomy group (n=15) as CKD animal model. The expressions of local IGF-1 and IGF-1 receptor (IGF-1R) of skeletal muscles were evaluated at the level of transcription and protein by real-time PCR and Western blotting. Results: There was no significant correlation between changes of serum IGF-1 level and estimated glomerular filtration rate (eGFR) (r=-0.066, P=0.307). However, after multivariable adjustment, serum IGFBP-3 increased with decreasing of eGFR (r=-0.181, P=0.005) in adult CKD patients. In multivariate analysis, age, eGFR, serum cholesterol level and 24 h urinary protein quantification were independent factors of serum IGFBP-3 in patients with CKD (R2=0.243, P<0.001). Animal experiments showed that the expression of IGF-1 mRNA and protein decreased in skeletal muscles of CKD rats. Expressions of IGF-1R mRNA and protein were slightly reduced and phosphorylation of IGF-1R was severely impaired in skeletal muscles of CKD rats. Conclusions: IGF-1 levels seem to be independent of renal function, but IGFBP-3 levels increased with decreasing of eGFR, which may cause a low affinity of IGF-1 with IGF-1R in skeletal muscles. Low affinity of IGF-1 with IGF-1R, as well as the decreasing of IGF-1 synthesis could lead to disorders of IGF-1R phosphorylation, and thus cause atrophy of skeletal muscles.

The deposition of Notch1 in hepatitis B virus-associated nephropathy and its role in hepatitis B virus X protein-induced epithelial-mesenchymal transdifferentiation and immunity disorder in renal tubular epithelial cells.

SUMMARY: Notch1 plays an important role in the regulation of immune responses and epithelial-mesenchymal transdifferentiation (EMT). Previous studies have observed inflammatory cell infiltration and tubulointerstitial fibrosis in the renal biopsies from patients with HBV-associated glomerulonephritis (HBV-GN). We hypothesized that Notch1 may be involved in the progression of HBV-GN. In this study, we evaluated the distribution of Notch1 in patients with HBV-GN. Our results showed that Notch1 was mainly distributed in renal tubules and the interstitial area, and the expression levels of Notch1 had a positive correlation with the renal tubular pathology. In this respect, we used human proximal tubular epithelial cells (HK-2) as target cells, which were transiently transfected with the hepatitis B virus X (HBx) gene using a eukaryotic vector. HBx expression resulted in significantly increased detection of Notch1, alpha-smooth muscle actin (α-SMA), major histocompatibility complex-II (MHC-II), CD40 and interleukin-4 (IL-4). At the same time, E-cadherin and interferon-γ (IFN-γ) expression levels were significantly inhibited. These HBx-induced phenotypes were exacerbated by upregulation of Notch1. Knock-down of Notch1 by specific shRNA caused decreases of α-SMA, MHC-II, CD40 and IL-4, and increases of E-cadherin and IFN-γ. These findings suggest that Notch1 is significantly associated with renal tubular and interstitial lesions. Notch1 can mediate HBx-induced EMT of HK-2 cells, promote HBx-induced increases in immune molecule expression and exacerbation of cytokine disorders, which may contribute to the progression of HBV-GN. Inhibitors of Notch1 signalling may be useful as new therapeutics for the treatment of HBV-GN.

Comprehensive analysis of patched domain-containing genes reveals a unique evolutionary pattern.

Patched domain-containing genes are members of a small family originally identified in Drosophila. A common feature of transmembrane patched domain-containing proteins is their function in the transport of sterols, sterol-modified proteins, and lipids. Recently, an expansion phenomenon of patched domain-containing genes was found in Caenorhabditis elegans; the major contributor to this higher number was patched-related (PTR) type genes. However, little is known about their expansion pattern and evolutionary origin. We performed a systematic genome-wide survey of patched domain-containing genes in species ranging from protozoa to vertebrates, as well as some plants. We found that patched domain-containing genes are conserved in plant and animal genomes and their expansion likely occurred in the early stages of nematode speciation. Based on analysis of phylogenetic and reconciled trees and calculation of synonymous substitutions, we discovered that the PTR genes appear to have experienced two expansions within a relatively short period after the speciation of nematodes. We also found that some patched domain-containing genes possessing a relatively recent evolutionary origin, such as PTR and PTCHD1, had fewer exons and shorter nucleotide coding sequence lengths compared with the older ones. It appears that the different types of patched domain-containing genes have different evolutionary patterns in different species.

[Research progresses on acute skin failure in children].

Acute skin failure (ASF) is an inevitable damage to the skin and subcutaneous tissue caused by hemodynamic instability and/or low perfusion. At present, there are some understandings and reports about adult ASF at home and abroad, but there are few reports about children's ASF. This article reviewed the definition, pathophysiological changes, risk factors, clinical manifestations, and management of children's ASF, and put forward suggestions in order to provide ideas for clinical diagnosis and treatment of children's ASF, and promote the further study of children's ASF.

Highly selective microbial transformation of major ginsenoside Rb1 to gypenoside LXXV by Esteya vermicola CNU120806.

AIMS: This study examined the biotransformation pathway of ginsenoside Rb(1) by the fungus Esteya vermicola CNU 120806. METHODS AND RESULTS: Ginsenosides Rb(1) and Rd were extracted from the root of Panax ginseng. Liquid fermentation and purified enzyme hydrolysis were employed to investigate the biotransformation of ginsenoside Rb(1) . The metabolites were identified and confirmed using NMR analysis as gypenoside XVII and gypenoside LXXV. A mole yield of 95·4% gypenoside LXXV was obtained by enzymatic conversion (pH 5·0, temperature 50°C). Ginsenoside Rd was used to verify the transformation pathway under the same reaction condition. The product Compound K (mole yield 49·6%) proved a consecutive hydrolyses occurred at the C-3 position of ginsenoside Rb(1) . CONCLUSIONS: Strain CNU 120806 showed a high degree of specific ß-glucosidase activity to convert ginsenosides Rb(1) and Rd to gypenoside LXXV and Compound K, respectively. The maximal activity of the purified glucosidase for ginsenosides transformation occurred at 50°C and pH 5·0. Compared with its activity against pNPG (100%), the ß-glucosidase exhibited quite lower level of activity against other aryl-glycosides. Enzymatic hydrolysate, gypenoside LXXV and Compound K were produced by consecutive hydrolyses of the terminal and inner glucopyranosyl moieties at the C-3 carbon of ginsenoside Rb(1) and Rd, giving the pathway: ginsenoside Rb(1) → gypenoside XVII → gypenoside LXXV; ginsenoside Rd→F(2) →Compound K, but did not hydrolyse the 20-C, ß-(1-6)-glucoside of ginsenoside Rb(1) and Rd. SIGNIFICANCE AND IMPACT OF THE STUDY: The results showed an important practical application on the preparation of gypenoside LXXV. Additionally, this study for the first time provided a high efficient preparation method for gypenoside LXXV without further conversion, which also gives rise to a potential commercial enzyme application.

Effect of Wnt signaling pathway on wound healing.

Wnt signaling pathway has been divided into two subclasses: the canonical pathway (Wnt/beta-catenin pathway) and the non-canonical pathway. It has been proven that Wnt/beta-catenin pathway can enhance wound healing, and some glycoprotein of Wnt family may directly or indirectly improve wound healing.

[Long-term results of multicenter study based on childhood acute lymphoblastic leukemia 2005 protocol].

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions: In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes.

Fifty-six patients with de novo acute myeloid leukemia M4/M5 subtypes were studied for rearrangements of the mixed lineage leukemia gene, MLL (also called HRX, Htrx-1, or ALL-1). Ten patients (18%) showed rearrangements of the MLL gene, 9 in a major breakpoint cluster region within a centromeric 8.3-kb BamHI fragment, whereas rearrangement in one patient was the result of a direct tandem duplication of exons 2-6 of MLL. Analysis of sequences at the duplication junction revealed that the points of MLL fusion within introns 6 and 1 both lie within Alu elements. This suggests the involvement of Alu repeat mediated homologous recombination in MLL self fusion. For the 10 rearranged samples, cytogenetics analysis revealed a normal karyotype in 3, and 3 had abnormalities other than 11q23. Survival analysis of patients revealed no difference between those with rearrangement of MLL and those showing the germ-line configuration.

Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion.

Infant acute leukemia (IAL) frequently involves breakage and recombination of the MLL gene with one of several potential partner genes. These gene fusions arise in utero and are similar to those found in leukemias secondary to chemotherapy with inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in utero exposures to chemicals may cause IAL via an effect on topo-II. We report a pilot case-control study of IAL across different countries and ethnic groups. Cases (n = 136) were population-based in most centers. Controls (n = 266) were selected from inpatients and outpatients at hospitals serving the same populations. MLL rearrangement status was derived by Southern blot analysis, and maternal exposure data were obtained by interviews using a structured questionnaire. Apart from the use of cigarettes and alcohol, very few mothers reported exposure to known topo-II inhibitors. Significant case-control differences were apparent for ingestion of several groups of drugs, including herbal medicines and drugs classified as "DNA-damaging," and for exposure to pesticides with the last two being largely attributable, respectively, to one nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68 for mosquitocidals, P = 0.003). Although it is unclear at present whether these particular exposures operate via an effect on topo-II, the data suggest that specific chemical exposures of the fetus during pregnancy may cause MLL gene fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based insecticides in certain settings, confirmation of these apparent associations is urgently required.

RT/PCR detection of SIL-TAL-1 fusion mRNA in Chinese T-cell acute lymphoblastic leukemia (T-ALL).

The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell acute lymphoblastic leukemias (T-ALL), this gene is disrupted in its 5' portion by a site-specific 100-kg deletion and is fused with the 5' part of the SIL gene, to form SIL-TAL-1 chimeric gene. In this study, we established a "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique which allows detection of the SIL-TAL-1 transcriptional expression. A chimeric mRNA was observed in four of 17 T-ALL cases and has been shown to result from the fusion between the exon 1 of SIL and exon 3 of TAL. A sensitivity test showed that this RT/PCR procedure could detect one leukemic cell among 10(6) normal cells. A positive RT/PCR result was obtained in two cases during clinical remission, suggesting the presence of minimal residual disease (MRD). One patient developed clinical relapse 3 months after PCR positivity. Moreover, analysis of the Tald rearrangement by DNA-based PCR in four patients with SIL-TAL-1 fusion revealed the type A (Tald1) rearrangement in all cases. Sequence analysis demonstrated the presence of N region and non-random "P" nucleotide, as well as base deletions at the genomic SIL-TAL-1 joining site. These data indicate that detection of TAL-1 gene abnormality is important for diagnosis and monitoring of MRD in a subset of T-ALL.

The influence of the extent of target organs on sensitivities of methods for screening rodent carcinogens.

Two hundred and thirty-three rodent carcinogens from the Carcinogenic Potency Database (CPDB) were analyzed with CASE (Computer Automated Structure Evaluation), and a comparison of the extents of target organs with the sensitivities for long-term carcinogenic bioassays in rats and mice, Salmonella assay (Sty), electrophilic substructure alert analysis (ESAA) and CASE was made. The carcinogenicity of 233 chemicals was evaluated in both rat and mouse bioassays. The present study showed that the sensitivities of the five methods for screening carcinogens were related to the extents of target organs of carcinogens. Among the carcinogens that did not induce tumors (extent = 0) in rats, the sensitivities of Sty and ESAA were 46 and 53, respectively. Among the carcinogens which induced tumors at a single organ (extent = 1) in rats, the sensitivities were 57 and 64 respectively; and 71 and 80 at multiple organs (extent > 1) respectively. The sensitivities of CASE were 76, 82, and 89 respectively at these three different extents. Similar results were obtained with these carcinogens in mice. The results indicate that mutagenic or electrophilic carcinogens are more likely to induce tumors at multiple target organs; in contrast, most carcinogens which induced tumors at only a single target organ in one species are rarely mutagenic or electrophilic. The sensitivities of Sty and ESAA were lower than that of the CASE method in these carcinogens. CASE analyzed chemical structures of many carcinogens and non-carcinogens and then established a database of key fragments, and its parameters are not only based on mutagenicity or electrophilicity of chemicals, and this resulted in a more exact detection of the carcinogenicity of chemicals with the CASE method.

The cervix-ripening effect of 15-methyl-prostaglandin F2 alpha methyl ester before vacuum aspiration for termination of early pregnancy in primigravidae.

A double blind clinical trial on prostaglandin for cervix ripening prior to vacuum aspiration for termination of early pregnancy in primigravidae was carried out in 68 patients with 6-11 week's gestation. The patients were randomly treated with either 1.0 mg of 15-methyl-prostaglandin F2 alpha methyl ester vaginal suppository or a placebo suppository. A mean cervical dilation to 6.6 mm was achieved with minimal side effects in the prostaglandin group as against 4.3 mm in the placebo group. The 15-methyl-prostaglandin F2 alpha methyl ester suppository technique seems to be effective, safe and simple in ripening the cervix for termination of early pregnancy in primigravidae.

Gamma and delta chain gene rearrangement of T cell receptor in acute lymphoblastic leukemia.

The immunophenotype, rearrangements of T cell receptor (TCR) gamma and delta chain genes as well as the immunoglobulin heavy chain (IgH) gene were studied in 37 cases of morphologically defined acute lymphoblastic leukemia (ALL). According to the expression of differentiation antigens, 8 cases were classified as T-ALL, 26 B lineage ALL, 2 acute undifferentiated leukemia (AUL) and myeloid phenotype. An order of TCR gene rearrangements was observed in T-ALL, with the rearrangement of delta gene preceding that of gamma gene. Both genes were also found frequently rearranged and/or deleted in high proportions of the ALL of B cell lineage. However, the patterns of gene rearrangements were somewhat different between the T and B lineage ALLs. In contrast, the IgH gene rearrangements were observed only in the B lineage ALL. The immunogenotype analysis of ALL proved to be a useful marker of the clonality and provided us with important information on early human lymphoid differentiation. We conclude that the determination of TCR gamma gene V-J junctional sequence can be used as clonal marker for detecting the minimal residual disease during clinical remission.

[A computer system of automated evaluation of structure-activity relationship of chemical mutagens].

A computer automated structure evaluation (CASE) system has been established. The data base of the system consists of more than 2000 chemicals and hundreds of biophores and biophobes identified by CASE. All programs can be run in micro-computer. Thus, entry of a chemical unknown genetoxity will result in the generation of all the possible fragments. On the basis of the presence and/or absence of these descriptors, CASE can predict activity or lack of it. In addition, and independently of the above, CASE also performs spell out, please and comparison program of genetic toxicology. The CASE program can be used to predict the mutagenicity and carcinogenicity of the many untested chemicals in the ambient environment. The sensitivity and specificity of this system all exceeds 90% and therefore the system has a very good-prospect of being used for forecasting.

[ARHI mRNA and protein expression in pancreatic cancers].

OBJECTIVE: To investigate ARHI mRNA and protein expression in pancreatic cancers. METHODS: Fifty-seven paraffin-embedded resected cancer samples and patient-corresponding normal pancreatic tissues were determined by using immunohistochemistry staining and in situ hybridization method. RESULTS: The positive rate of ARHI mRNA and protein expression in normal control pancreatic tissue was 84.2% and 82.5% respectively, and in cancer group was 52.6% both. The positive rate of mRNA and protein expression in cancer group was markedly decreased (P < 0.01). Yet the protein expression correlated with mRNA. Furthermore, positive staining of ARHI protein and mRNA can be observed in duodenal mucus epithelium, fibroblasts, smooth muscle myocytes, and wall of blood vessels. There was no correlation between positive rate and cancer differentiation, or clinical stages. CONCLUSIONS: ARHI protein expression is down-regulated in pancreatic cancer, possibly plays a role as tumor suppress gene, ARHI protein expressed in multiple types of tissues including duodenal mucus epithelium, fibroblasts and so on.

Detection of marginal leakage of Class V restorations in vitro by micro-computed tomography.

This in vitro study evaluated the efficacy of micro-computed tomography (CT) in marginal leakage detection of Class V restorations. Standardized Class V preparations with cervical margins in dentin and occlusal margins in enamel were made in 20 extracted human molars and restored with dental bonding agents and resin composite. All teeth were then immersed in 50% ammoniacal silver nitrate solution for 12 hours, followed by a developing solution for eight hours. Each restoration was scanned by micro-CT, the depth of marginal silver leakage in the central scanning section was measured, and the three-dimensional images of the silver leakage around each restoration were reconstructed. Afterward, all restorations were cut through the center and examined for leakage depth using a microscope. The silver leakage depth of each restoration obtained by the micro-CT and the microscope were compared for equivalency. The silver leakage depth in cervical walls observed by micro-CT and microscope showed no significant difference; however, in certain cases the judgment of leakage depth in the occlusal wall in micro-CT image was affected by adjacent enamel structure, providing less leakage depth than was observed with the microscope (p<0.01). Micro-CT displayed the three-dimensional image of the leakage around the Class V restorations with clear borders only in the dentin region. It can be concluded that micro-CT can detect nondestructively the leakage around a resin composite restoration in two and three dimensions, with accuracy comparable to that of the conventional microscope method in the dentin region but with inferior accuracy in the enamel region.

Endostar combined with chemotherapy compared with chemotherapy alone in the treatment of nonsmall lung carcinoma: A meta-analysis based on Chinese patients.

INTRODUCTION: Lung cancer is the leading cause of cancer-associated death world-wide. And the lung cancer is generally divided into small cell lung carcinoma and non-small cell lung cancer. For advanced NSCLC, the chemotherapy and target therapy were the important treatment modality. This meta-analysis was to evaluate the clinical efficacy and toxicity between endostar combined chemotherapy and chemotherapy alone in Chinese patients. MATERIALS AND METHODS: We searched the PubMed, EMBASE, and CNKI databases to find the potential relevant articles reporting the endostar combined with chemotherapy regimen in the treatment of nonsmall cell lung cancer in Chinese patients. The tumor response and toxicity difference between the two groups were demonstrated by odds ratio (OR) and its 95% confidence interval (95% CI). All the data was pooled by Stata 11.0 (http://www.stata.com; Stata Corporation, College Station, TX) software. RESULTS: We included 14 studies published in Chinese or English studies. The pooled results showed adding endostar in the chemotherapy regimen can significant increase the objective response rate (OR = 2.42, 95% CI = 1.87-3.12, P = 0.00) and disease control rate (OR = 2.22, 95% CI = 1.68-2.94, P = 0.00). For toxicities, the pooled data showed no statistical difference for grade III-IV granulocytopenia risk (OR = 1.04, 95% CI = 0.74-1.44, P = 0.83). Nausea and vomiting (OR = 0.93 95% CI: 0.51-1.52, P = 0.78) and grade III-IV alopecia (OR = 0.99, 95% CI: 0.76-1.29, P = 0.95). The funnel plot showed no statistical publications. CONCLUSION: Combined treatment with endostar can improve the response rate for NSCLC patients without increasing the risk of developing severe adverse event.

Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases.

The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.

Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries.

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically correlated (P<0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20-38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4-11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.