Achieve fairness without demographics for dermatological disease diagnosis.

In medical image diagnosis, fairness has become increasingly crucial. Without bias mitigation, deploying unfair AI would harm the interests of the underprivileged population and potentially tear society apart. Recent research addresses prediction biases in deep learning models concerning demographic groups (e.g., gender, age, and race) by utilizing demographic (sensitive attribute) information during training. However, many sensitive attributes naturally exist in dermatological disease images. If the trained model only targets fairness for a specific attribute, it remains unfair for other attributes. Moreover, training a model that can accommodate multiple sensitive attributes is impractical due to privacy concerns. To overcome this, we propose a method enabling fair predictions for sensitive attributes during the testing phase without using such information during training. Inspired by prior work highlighting the impact of feature entanglement on fairness, we enhance the model features by capturing the features related to the sensitive and target attributes and regularizing the feature entanglement between corresponding classes. This ensures that the model can only classify based on the features related to the target attribute without relying on features associated with sensitive attributes, thereby improving fairness and accuracy. Additionally, we use disease masks from the Segment Anything Model (SAM) to enhance the quality of the learned feature. Experimental results demonstrate that the proposed method can improve fairness in classification compared to state-of-the-art methods in two dermatological disease datasets.

Comparison of modified Furlow palatoplasty using small double-opposing Z-plasty and conventional Furlow palatoplasty: A long-term outcome study.

BACKGROUND: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center. METHODS: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included. RESULTS: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0. CONCLUSION: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula.

New-Onset Atrial Fibrillation Is a Red Flag to Microvascular Free Tissue Transfer Failure in Head and Neck Cancer Patients.

BACKGROUND: Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. METHODS: We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. RESULTS: In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p < 0.001) compared to those without AF or new-onset AF. CONCLUSION: Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

Cimetidine Attenuates Therapeutic Effect of Anti-PD-1 and Anti-PD-L1 and Modulates Tumor Microenvironment in Colon Cancer.

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Influence of verbal instruction on gait training in Parkinson's disease: a randomized controlled trial.

OBJECTIVE: Verbal instruction is one of the most commonly used methods that therapists use to correct walking pattern for people with Parkinson's disease (PD). This study aimed to compare the long-term training effects of two different verbal instructions that either asked the participants to 'take big steps' or 'strike the ground with the heel' on walking ability in individuals with PD. DESIGN: Forty-five participants with PD were randomized into the big-step (BIG) or heel strike (HS) group. The participants underwent 12 sessions of treadmill and overground gait training. Throughout the interventions, the BIG group received an instruction to 'take big steps,' while the HS group received an instruction to 'strike the ground with your heel.' The primary outcome was gait performance, including velocity, stride length, cadence, and heel strike angle. The participants were assessed before, immediately after, and 1-month after training. RESULTS: Both groups showed significant improvements in gait performance after training. The HS group showed continuous improvements in velocity and stride length during the follow-up period; however, the BIG group showed slightly decreased performance. CONCLUSION: A verbal instruction emphasizing heel strike can facilitate long-term retention of walking performance in people with PD.

Effect of bone marrow aspiration concentrate and platelet-rich plasma combination in anterior cruciate ligament reconstruction: a randomized, prospective, double-blinded study.

BACKGROUND: The effect of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) combination in enhancing graft maturation and tendon-bone tunnel interfacial healing after anterior cruciate ligament (ACL) reconstruction remains unclear. We hypothesised that BMAC and PRP combination could lead to better clinical results and better graft maturation/interface healing than PRP alone or conventional ACL reconstruction without any other biologic augmentation. METHODS: In this randomised double-blind prospective study, patients undergoing ACL reconstruction surgery were randomly assigned into three groups: (1) control group (without any biologic augmentation), (2) PRP treatment group, and (3) combined BMAC and PRP (BMAC + PRP) group. Moreover, they were evaluated using the clinical functional score, laxity examination, and magnetic resonance imaging (MRI) analysis. RESULTS: No significant difference was observed in the improvement of functional scores among groups. However, laxity improvement at 24 weeks showed a significant difference with the BMAC + PRP group having the lowest laxity. MRI analysis showed no significant change in whole graft maturation among groups. In particular, the BMAC + PRP group showed delayed signal peak and higher graft signal at 24 weeks compared with the other two groups; however, the difference was not significant. With regard to tendon-bone interfacial healing, the BMAC + PRP group showed significantly wider tendon-bone interface in the femoral bone tunnel at 24 weeks compared with the other two groups. Moreover, the BMAC + PRP group showed significantly higher peri-tunnel edema signal in the femoral bone tunnel at 12 weeks compared with the other two groups. CONCLUSION: PRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon-bone interfacial healing compared with control (no additional treatment). When BMAC is used in ACL reconstruction, the possibility of greater inflammation in the early stage to graft maturation and bone tunnel healing should be considered.

Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Impact of reduced margin pelvic radiotherapy on gastrointestinal toxicity and outcome in gynecological cancer.

Purpose: To investigate the effect of reduced margin pelvic radiotherapy on gastrointestinal toxicity and outcomes in gynecological cancer. Materials and methods: This retrospective study analyzed data of 590 patients who underwent hysterectomy and adjuvant pelvic radiotherapy between 2010 and 2020 at two tertiary centers. The pelvic nodal region was delineated based on a reduced margin definition or the Radiation Therapy Oncology Group (RTOG) guidelines. All patients were treated with intensity-modulated radiotherapy with imaging guidance. Gastrointestinal toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and the Patient-Reported Outcome version (PRO-CTCAE). Results: Overall, 352 (59.7%) and 238 (40.3%) patients underwent RTOG and reduced margin pelvic radiotherapy, respectively. Median follow-up was 6.4 years (IQR: 3.7-9.6). Reduced margin pelvic radiotherapy significantly lowered the radiation dose to the small bowel. For CTCAE grade ≥ 2 or 3, acute gastrointestinal toxicity was lower in the reduced margin group than in the RTOG group (16.4% vs. 33.5%, p < 0.001; 2.9% vs. 8.5%, p < 0.001). The reduced margin group reported less severe acute gastrointestinal toxicity (PRO-CTCAE score ≥ 3) than the RTOG group (12.5% vs. 28.7%, p < 0.001). Late grade 3 gastrointestinal toxicity was lower in the reduced margin group than in the RTOG group (0.8% vs. 4.8%, p = 0.006). The 5-year pelvic recurrence-free survival and disease-free survival in the RTOG and reduced margin pelvic radiotherapy groups were 97.4% and 97.9% (p = 0.55) and 80.7% and 83.5% (p = 0.18), respectively. Conclusion: Reduced margin pelvic radiotherapy decreased acute and late gastrointestinal toxicity and achieved favorable outcomes.

A technique to convert a 3D printed cast used in the fabrication of an interim implant-supported crown into a definitive cast capturing the acquired emergence profile.

An esthetic peri-implant soft tissue contour is a critical element of the success of implant restorations in the esthetic zone. Once the optimal transmucosal soft tissue profile is formed, it needs to be accurately replicated on the master cast. This clinical technique involves the utilization of a silicone putty positioning index placed in the patient's mouth to accurately duplicate the external contour of teeth and soft tissue. By combining this positioning index with the implant-supported interim crown, the 3D-printed initial cast, which was used to fabricate the interim crown, can be conveniently and efficiently transformed into a definitive master cast.

The outcomes and prognostic factors of patients with hepatocellular carcinoma and Child-Turcotte-Pugh class B.

BACKGROUND: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients. METHODS: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0. RESULTS: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score. CONCLUSION: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.

Real-Time Tracking of Laryngeal Motion via the Surface Depth-Sensing Technique for Radiotherapy in Laryngeal Cancer Patients.

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left-right, cranio-caudal, and anterior-posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were -0.7 ± 1.0 mm (-18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left-right, cranio-caudal, and anterior-posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.

Triage policy to postpone endoscopy for patients with low-risk varices is safe during the lockdown period of COVID-19 pandemic.

BACKGROUND & AIMS: During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended. We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic. METHODS: Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. One experienced gastroenterologist reviewed the prior-scheduled list of patients for the EVL prophylaxisprogram. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020. RESULTS: Of the 124 patients receiving EVL, a higher percentage of esophageal variceal bleeding (EVB) was noted (9/32, 28.1% vs. 8/92, 8.7%, p = 0.006) during the lockdown period, with a higher percentage of EVB in the referrals (7/9, 77.8% vs. 2/14, 14.2%, p = 0.007). Among patients who received prophylactic EVL, 6 of 78 (7.7%) experienced EVB during the normal period, which is no different to 2 of 23 (8.7%) during the lockdown period. Twenty-three patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB during the lockdown period. Child-Turcotte-Pugh (CTP) class C was predictive of EVB (relative risk 8.400, P = 0.033), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.016, P = 0.002). CONCLUSION: Entrance into the prophylaxis program does not only decreases risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period.

Effectiveness of betadine-coating gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy: a randomized controlled trial.

BACKGROUND: Peristomal wound infection is a common complication in patients receiving percutaneous endoscopic gastrostomy (PEG). The main reason for peristomal infection might be the oral microbes coating the gastrostomy tube during implantation. Povidone-iodine solution can be applied for skin and oral decontamination. We designed a randomized controlled trial to test the effectiveness of a Betadine® (povidone-iodine) coated gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy. METHODS: A total of 50 patients were randomized to Betadine and control groups (25 patients in each group) from April 2014 to August 2021 at a tertiary medical center. All patients received the pull method for PEG implantation using a 24-french gastrostomy tube. The primary endpoint was peristomal wound infection rate 2 weeks after the procedure. RESULTS: Changes in Neutrophil/Lymphocyte ratio (N/L ratio) and C-Reative protein (Delta CRP) at 24 h after PEG were higher in the control group than in the Betadine group (N/L ratio, 3.1 vs. 1.2, p = 0.047; CRP, 2.68 vs.1.16, p = 0.009). The two groups did not differ in post-PEG fever, peristomal infection, pneumonia, or all-cause infection. Delta CRP could predict peristomal infection and all-cause infection within 2 weeks (AUROC 0.712 vs. 0.748; p = 0.039 vs. 0.008). The best cut-off-point of Delta CRP for the diagnosis of peristomal wound infection was 3 mg/dl. CONCLUSION: The betadine coating gastrostomy tube method could not reduce peristomal infection after percutaneous endoscopic gastrostomy. CRP elevation of less than 3 mg/dl may be used to exclude the potential peristomal wound infection. TRIAL REGISTRATION: NCT04249570 ( https://clinicaltrials.gov/ct2/show/NCT04249570 ).

Anti-Cancer Effects of Oxygen-Atom-Modified Derivatives of Wasabi Components on Human Leukemia Cells.

1-Isothiocyanato-6-(methylsulfinyl)-hexanate (6-MITC) is a natural compound found in Wasabia japonica. The synthetic derivatives 1-Isothiocyanato-6-(methylsulfenyl)-hexane (I7447) and 1-Isothiocyanato-6-(methylsulfonyl)-hexane (I7557) were obtained from 6-MITC by deleting and adding an oxygen atom to the sulfone group, respectively. We previously demonstrated that extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation were induced by 6-MITC and inhibited the viability of human chronic myelogenous leukemia K562 cells. In this study, we examined the anti-cancer effects of 6-MITC derivatives on human chronic myelogenous leukemia (CML) cells. Autophagy was identified as the formation of autophagosomes with double-layered membranes using transmission electron microscopy. Cell cycle and differentiation were analyzed using flow cytometry. Apoptosis was detected by annexin V staining. After treatment with I7447 and I7557, the G2/M phase of cell cycle arrest was revealed. Cell death can be induced by a distinct mechanism (the simultaneous occurrence of autophagy and aberrant mitosis). The expression levels of acridine orange were significantly affected by lysosomal inhibitors. The natural wasabi component, 6-MITC, and its synthetic derivatives have similar effects on human chronic myelogenous leukemia cells and may be developed as novel therapeutic agents against leukemia.