Development, Validation, and Comparison of 2 Ultrasound Feature-Guided Machine Learning Models to Distinguish Cervical Lymphadenopathy.

ABSTRACT: The objective of this study is to develop and validate the performance of 2 ultrasound (US) feature-guided machine learning models in distinguishing cervical lymphadenopathy. We enrolled 705 patients whose US characteristics of lymph nodes were collected at our hospital. B-mode US and color Doppler US features of cervical lymph nodes in both cohorts were analyzed by 2 radiologists. The decision tree and back propagation (BP) neural network were developed by combining clinical data (age, sex, and history of tumor) and US features. The performance of the 2 models was evaluated by calculating the area under the receiver operating characteristics curve (AUC), accuracy value, precision value, recall value, and balanced F score (F1 score). The AUC of the decision tree and BP model in the modeling cohort were 0.796 (0.757, 0.835) and 0.854 (0.756, 0.952), respectively. The AUC, accuracy value, precision value, recall value, and F1 score of the decision tree in the validation cohort were all higher than those of the BP model: 0.817 (0.786, 0.848) vs 0.674 (0.601, 0.747), 0.774 (0.737, 0.811) vs 0.702 (0.629, 0.775), 0.786 (0.739, 0.833) vs 0.644 (0.568, 0.720), 0.733 (0.694, 0.772) vs 0.630 (0.542, 0.718), and 0.750 (0.705, 0.795) vs 0.627 (0.541, 0.713), respectively. The US feature-guided decision tree model was more efficient in the diagnosis of cervical lymphadenopathy than the BP model.

When is the best time and grade to start ruxolitinib in corticosteroid-refractory acute graft-versus-host-disease: A multi-center research.

OBJECTIVE: Ruxolitinib was recently approved to treat corticosteroid-resistant acute graft-versus-host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy. METHODS: Retrospective, observational multi-center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24). RESULTS: In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25). CONCLUSIONS: Our data suggest that starting ruxolitinib in ≤ 7 days of declaring corticosteroid failure regardless of G vHD grade improves complete response rate but not OR rates. Starting ruxolitinib at grade I and within 7 days may get a more significant response.

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

[Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1].

OBJECTIVE: To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1). METHODS: Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay. RESULTS: The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) µg/ml, which was significantly lower than (0.301±0.04) µg/ml of CA46-C23-KNC cells and (0.338±0.05) µg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle. CONCLUSION: The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.

5-Aza-dC promotes T-cell acute lymphoblastic leukemia cell invasion via downregulation of DNMT1 and upregulation of MMP-2 and MMP-9.

5-Aza-2'-deoxycytidine (5-Aza-dC) is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells, and can restore the expression of their target genes in Jurkat cells. The goal of this study was to discern the potential effect of 5-Aza-dC on the invasion of T-ALL cells in acute lymphoblastic leukemia (ALL). The role of matrix metallopeptidase (MMP)-2, MMP-9, and DNMT1 in cell invasion was determined using loss- and gain-of-function investigations in Jurkat- and Sup-T1-R cells. A nude mouse model of ALL was established for further exploration of their roles in vivo. MMP-2 and MMP-9 exhibited high expression and low DNA methylation levels in 5-Aza-dC-resistant T-ALL cells. DNMT1 was poorly expressed in 5-Aza-dC-resistant T-ALL cells and exhibited decreased enrichment in the promoter region of MMP-2 and MMP-9. Silencing of MMP-2 and MMP-9 or DNMT1 overexpression reduced T-ALL cell invasion. After treatment of Sup-T1 cells with 5-Aza-dC, MMP-2 and MMP-9 presented with reduced DNA methylation levels but increased expression, and DNMT1 expression was identified to be suppressed. Further, in vivo assays revealed that DNMT1 alleviated T-ALL by reducing the expression of MMP-2 and MMP-9 in vivo. All in all, 5-Aza-dC activates MMP-2 and MMP-9 expression by reducing DNMT1-dependent DNA methylation levels and, hence, promotes the invasion of T-ALL cells.

Circ_0003645 serves as miR-335-5p sponge to promote the biological process of diffuse large B-cell lymphoma by upregulating NFIB.

BACKGROUND: Circular RNAs (circRNAs) are critical regulators for the development of many tumours, including diffuse large B-cell lymphoma (DLBCL). However, the role and mechanism of circ_0003645 in DLBCL progression remains obscure. METHODS: Quantitative real-time PCR was performed to measure the expression of circ_0003645, microRNA (miR)-335-5p and nuclear factor I/B (NFIB). Cell viability, apoptosis and cell cycle were measured by cell counting kit 8 assay and flow cytometry. Protein expression was assessed using western blot analysis, and cell glycolysis was evaluated by detecting glucose consumption and ATP/ADP ratios. Besides, dual-luciferase reporter assay and RIP assay were used to confirm RNA interaction. RESULTS: Our data showed that circ_0003645 expression was significantly upregulated in DLBCL tumour tissues. After circ_0003645 knockdown, the viability, cell cycle and glycolysis of DLBCL cells were inhibited, while cell apoptosis was promoted. MiR-335-5p could be sponged by circ_0003645, and NFIB was confirmed to be a downstream target of miR-335-5p. Function analysis revealed that anti-miR-335-5p reversed the regulation of si-circ_0003645 on DLBCL cell progression, and NFIB overexpression also abolished miR-335-5p-mediated the biological functions of DLBCL cells. CONCLUSION: The present study revealed that circ_0003645 promoted the proliferation and glycolysis of DLBCL cells by the miR-335-5p/NFIB axis, which might provide a novel insight for DLBCL treatment.

DNA methylation-mediated silencing of microRNA-204 enhances T cell acute lymphoblastic leukemia by up-regulating MMP-2 and MMP-9 via NF-κB.

T cell acute lymphoblastic leukaemia (T-ALL) is a highly aggressive haematological cancer of the bone marrow. The abnormal expression of microRNAs (miRNAs) is reportedly involved in T-ALL development and progression. Thus, we aimed to decipher the involvement of miR-204 silencing mediated by DNA methylation in the occurrence of T cell acute lymphoblastic leukaemia (T-ALL). miR-204 expression was determined in bone marrow and peripheral blood samples from T-ALL patients by real-time quantitative PCR (RT-qPCR) with its effect on cell proliferation evaluated by functional assays. In addition, bisulphite sequencing PCR was employed to detect the DNA methylation level of the miR-204 promoter region, and the binding site between miR-204 and IRAK1 was detected by luciferase assay. We found that miR-204 was down-regulated in T cells of T-ALL patients, which was caused by the increased DNA methylation in the promoter region of miR-204. Moreover, overexpression of miR-204 inhibited T-ALL cell proliferation while enhancing their apoptosis through interleukin receptor-associated kinase 1 (IRAK1), which enhanced the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 through activation of p-p65. Thus, miR-204 modulated MMP-2 and MMP-9 through IRAK1/NF-κB signalling pathway, which was confirmed by in vivo assay. Taken together, DNA methylation-mediated miR-204 silencing increased the transcription of IRAK1, thus activating the NF-κB signalling pathway and up-regulating the downstream targets MMP-2/MMP-9.

[PLK1 Expression in Mantle Cell Lymphoma and Its Clinical Significance].

OBJECTIVE: To explore the expression level of PLK1 in mantle cell lymphoma(MCL), and the effect of silencing PLK1 gene by RNA interference on the cell proliferation, apoptosis, and cell cycle. METHODS: S-P immunohistochemistry technique was used to detect the expression of PLK1 in tissues of 42 patients with MCL and 30 patients with reactive proliferative lymphodenitis(RPL), their expression levels were compared and analyzed. The Jeko-1 cells were transfected with lentivirus contaiming PLK-1 shRNA, then the mRNA and protein expression of PLK-1 was detected by real-time guantitative PCR and Western blot nespectively, and the silencing efficacy of PLK-1 shRNA was identificd. The cell proliferation was detected by CCK method, the cell apoptosis was detected by Annexin V/PI double staining, the cell cycle was detected by PI single staining, the changes of apoptosis-related proteins BAX, BCL-2 and Caspase 3 were detected by Western blot. RESULTS: The positive expression rate of PLK-1 in tissue of MCL patients was 66.67%(28/42), which was significanfly higher than 20%(6/30) in tissue of RPL patients (P＜0.05). The PLK-1 positive expression correlated with B symptom, IPI score, Ann-Arbor stage(P＜0.05). After infection of Jeko-1 cells with lentivirus containing PLK-1 shRNA for 72 hours, the mRNA and protein expressions of PLK-1 were significantly down-regulated(P＜0.05), the proliferation rate of cells in group of PLK-1 shRNA was significanly lower than that in control and Neg shRNA groups(P＜0.05); the apoptosis rate of cells in PLK-1 shRNA group was (27.42±3.44)%, which was significantly higher than that in control group (1.23±0.42)% and Neg shRNA group (2.07±0.58) % (P＜0.05). The cell cycle analysis showed that the cell ratio in G2/M phase of PLK-1 shRNA group was (27.21±3.59) %, which was higher than that in control group (13.28±2.63)% and Neg shRNA group (14.34±2.37) %. The detection of apoptosis-related proteins showed that the expression of BAX was up-regulated, the expression of BCL-2 was down-regnlated and the expression of caspase 3 was up-regulated. CONCLUSION: The PLK-l overexpression appears in tissue of MCL patients. The silencing PLK-1 gene can inhibit the proliferation of Jeko-1 cells, induce the apopotosis of Jeko-1 cells and arrestes cell cycle in G2/M phase.

G-CSF-primed haplo-identical HSCT with intensive immunosuppressive and myelosuppressive treatments does not increase the risk of pre-engraftment bloodstream infection: a multicenter case-control study.

A multicenter retrospective study in 131 patients (44 females/87 males) with hematological disorders who underwent G-CSF-primed/haplo-identical (Haplo-ID) (n = 76) or HLA-identical (HLA-ID) HSCT (n = 55) from February 2013 to February 2016 was conducted to compare the incidence and risk factors for pre-engraftment bloodstream infection (PE-BSI). In the Haplo-ID group, 71/76 patients with high-risk (n = 28) or relapsed/refractory hematological malignancies (n = 43) received FA5-BUCY conditioning (NCT02328950). All received trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Blood cultures and catheter tip cultures were obtained to confirm the BSI. PE-BSI was detected in 24/131 HSCT patients (18/76 in Haplo-ID and 6/55 in HLA-ID) after 28 febrile neutropenic episodes. Among 28 isolates for the 24 patients, 21 (75%) were Gneg bacteria, 6 (21.4%) Gpos and 1 (3.6%) fungi. Bacteria sources were central venous line infection (7/29.2%), gastroenteritis (6/25%), lower respiratory tract infection (LRTI; 5/20.8%), perianal skin infection (4/16.7%), and unknown (2/8.3%). The duration of neutropenia (P = 0.046) and previous Gneg bacteremia (P = 0.037) were important risk factors by univariate analysis, while the type of HSCT was not. A trend of TMP-SMX-resistant BSI in both groups may be due to routine antibacterial prophylaxis strategies. Our data show that G-CSF-primed Haplo-ID HSCT did not increase the risk of PE-BSI, even with intensive immunosuppressive treatments.

The Relationship Between MMP-2 -1306C>T and MMP-9 -1562C>T Polymorphisms and the Risk and Prognosis of T-Cell Acute Lymphoblastic Leukemia in a Chinese Population: A Case-Control Study.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. Hence, our study aims to investigate the relationship between MMP-2 -1306C>T and MMP-9 -1562C>T polymorphisms and the risk and prognosis of T-ALL. METHODS: From April 2009 to February 2011, a total of 376 T-ALL patients were chosen as the case group. Meanwhile, 352 healthy people who passed routine health examinations were selected as the control group. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the frequency of MMP-2 -1306C>T (rs243865) and MMP-9 -1562C>T (rs3918242) polymorphisms in the study subjects. The serum levels of MMP-2 and MMP-9 were detected using enzyme-linked immunosorbent assay (ELISA). A Kaplan-Meier analysis was employed to analyze the event-free survival (EFS) rates of the T-All patients with different MMP-2 and MMP-9 genotypes. A multivariate COX model was applied to analyze the relationship between MMP-2 and MMP-9 polymorphisms and the prognosis of T-ALL patients. A C-statistic and net reclassification index (NRI) was carried out to evaluate the predictive value of MMP-2 and MMP-9 gene polymorphisms using the Cox model. RESULTS: Compared to the control group, the genotypic frequency of MMP-2 -1306C>T (CT + TT) and MMP-9 -1562C>T (CT + TT) in the case group was significantly higher. The serum level of MMP-9 was markedly elevated in T-ALL patients with the CT + TT genotype compared to patients with the CC genotype. The results of the Kaplan-Meier analysis showed that the median EFS was lower in T-ALL patients with the CT + TT genotype of MMP-9 -1562C>T compared to patients with the CC genotype. The results of a multivariate analysis using the Cox proportional hazard model indicated that the MMP-9 -1562C>T polymorphism was associated with the prognosis of T-ALL patients. CONCLUSION: These results indicated that MMP-2 -1306C/T and MMP-9 -1562C/T polymorphisms might be associated with an increased risk of T-ALL. The MMP-9 -1562C>T polymorphism may also be related to the prognosis of T-ALL patients.

Effects of Blood Purification on Serum Levels of Inflammatory Cytokines and Cardiac Function in a Rat Model of Sepsis.

OBJECTIVE: The study aimed to explore the effects of blood purification (BP) on serum levels of inflammatory cytokines and cardiac function in a rat model of sepsis. METHODS: A rat model of sepsis was established by cecal ligation and puncture. All rats were divided into the normal control, sham operation, model, sham treatment, and BP treatment groups. Cardiac functions, inflammatory cytokines, myocardial enzymes, pathological score of cardiac muscle tissue, and myocardial apoptosis of rats in each group were compared. RESULTS: Sepsis rats had higher serum levels of inflammatory cytokines and lower cardiac function than those in the normal control and sham operation groups. Compared with the model and sham treatment groups, improved cardiac functions, decreased inflammatory cytokines, myocardial enzymes, pathological score, and myocardial apoptosis and mortality were observed in the BP treatment group. CONCLUSION: BP may reduce serum levels of inflammatory cytokines and improve cardiac function of sepsis rats.

The Transcriptome Study of Subtype M2 Acute Myeloblastic Leukemia.

Our objective is to explore the tumor-specific mutated genes by transcriptome sequencing of patients with acute myeloblastic leukemia. 96 patients with subtype M2 acute myeloid leukemia (AML), admitted during January 2007 to January 2012, were selected. Bone marrow and peripheral blood samples from the patients after the first visit and the patients who were improved or alleviated, were subjected to high-throughput sequencing to compare the gene expression. The single nucleotide mutation related to subtype M2 AML was detected. Meanwhile, real-time fluorescent quantitation RT-PCR was used to detect the AML1/ETO fusion gene and its correlation with prognosis after treatment. Among 96 patients, AML1-ETO fusion gene was positive in 52 cases, the positive rate was 54.17 %. The complete relief (CR) rate of AML1-ETO fusion gene positive patients was 84.62 %, and the CR rate of AML1/ETO fusion gene negative patients was 77.27 %; the CR rate of AML1-ETO positive patients was higher than that of patients without the fusion gene, however there was no statistical difference. In the analysis of recurrent gene mutation in AML-M2 patients, IDH2, ASXL1, TET2, JAK1 and JAK2 gene expressions were not significantly different before treatment and after CR, however, IDHI, JAK3, ABL1 and BCR gene expressions were significantly different. In the study of transcriptome in AML-M2 patients, high-throughput sequencing could effectively detect the difference of the gene expression before treatment and after CR. Furthermore, positive expression of AML1-ETO fusion gene had effect on the prognosis of patients.

[Inhibitory effect of VPA on multiple myeloma U266 cell proliferation and regulation of histone acetylation].

This study was aimed to investigate the effects of sodium valproate (VPA) on the proliferation and regulation of histone acetylation of multiple myeloma cell line U266. U266 cells were treated with VPA. Cell proliferation was determined by CCK-8 assay, and cell cycle were analyzed by flow cytometry (FCM). The expression level of HDAC1 mRNA was detected by RT-PCR, and the protein levels of HDAC1 and histone H3, H4 acetylation was detected by Western blot. The results showed that the VPA inhibited the proliferation of U266 cells in concentration-and time-dependent manners.After exposure to different concentrations of VPA for 48 hours, the proportion of G(0)/G(1) cells increased, while the proportion of S phase cells decreased. The cell cycle was arrested obviously in G(0)/G(1) phase (p < 0.05). The expression of HDAC1 mRNA was inhibited, and the protein level of HDAC1 was down-regulated, while the histone H3/H4 acetylation was up-regulated in U266 cells. It is concluded that the VPA can inhibit cell proliferation of U266 and induce G(0)/G(1) phase arrest. The increase of histone H3/H4 acetylation resulting from inhibiting HDAC1 by VPA might be considered as a possible mechanism.

[Investigation on the mechanisms of p15INK4B gene demethylation by valproate in Molt-4 cells].

OBJECTIVE: To study the antitumour effects of sodium valproate (VPA) on the proliferation, differentiation and cell cycle of Molt-4 cell and to investigate its demethylation mechanisms. METHODS: After Molt-4 cells trated with VPA at different concentrations, cell viability and growth curve were assessed by MTT assay. Cell cycle changes were analyzed by flow cytometry. The expression level of p15, DNA methyltransferase 1 (DNMT-1), DNMT3A and 3B mRNA were detected by RT-PCR and the methylation level was detected by hn-MSPCR. RESULTS: VPA significantly inhibited the proliferation of Molt-4 cells. After 48 h culture with 5.0 mmol/L VPA, the percentages of Molt-4 cells in G(0)/G(1) phase was (66.87 ± 3.31)% and in S phase was (8.47 ± 2.56)%, while in control group, the cells in G(0)/G(1) phase increased and in S phase decreased significantly. The p15 gene in Molt-4 cells failed to express due to its hypermethylation. The expression level of p15 gene mRNA increased significantly after exposure to VPA for 48 h. As compared with control group, the expression of DNMT-1 was down-regulated in a dose-dependent manner. The expression level of DNMT3B decreased at 10.0 mmol/L concentration. CONCLUSION: VPA has a demethylation effect on p15 INK4B gene by inhibiting the DNMT-1 and DNMT3B gene activities to recover p15 gene activity, which arrests Molt-4 cell in G(0)/G(1) phase.

[Synergistic effects of VPA and As2O3 on Molt-4 cells in vitro and its possible mechanisms].

This study was purposed to investigate the synergistic effects of sodium valproate (VPA) and As2O3 on the proliferation of Molt-4 cells in vitro and its possible mechanisms. Cell viability and growth curve were assessed by the MTT assay. The synergistic activity in combination of 2 drugs was determined by the Q format. The expression levels of p15, DNA methyltransferase 1 (DNMT-1), DNMT3A and DNMT 3B mRNA were detected by RT-PCR and the methylation level was detected by hn-MSPCR. The results indicated that the VPA and As2O3 both inhibited proliferation of Molt-4 cells. The combination of two drugs showed an additive effect (values of Q were>or=0.85). The inhibitory rate in combination of 5 mmol/L of VPA with 10 micromol/L of As2O3 was (70.31+/-2.54)%. The p15 gene in Molt-4 cell line failed to express due to its hypermethylation. The level of p15 gene mRNA expression increased significantly after exposure to VPA in combination with As2O3 for 48 h. As compared with control group, the expression of DNMT-1 was down-regulated in a dose-dependent manner, whereas DNMT3A had no significant differences from the control. The level of expression of DNMT3B seemed to decrease at 10 mmol/L concentration. There were significant differences between the combination of the two drugs and the control group. The gray value of methylated bands decreased after the treatment of VPA alone and in combination with As2O3 in a dose-dependent manner. It is concluded that VPA induces demethylation of p15 INK4B gene by inhibiting the DNMT-1 and DNMT3B gene activities, which up-regulates the p15 gene, recovers its activity. The combination of VPA with As2O3 has the synergistic additive effect on the inhibition of cell viability, so that VPA can reduce the side effect of As2O3 on liver function, which would be verified in the clinical practice.