[Progress in Image-planned and Real-time Image-guided Lung Cancer Biopsy 
in the Detection of Biomarkers].

With the progress of targeted therapy and immunotherapy for lung cancer, the clinical demand for lung biopsy is increasing. An ideal biopsy specimen can be used not only for histopathological diagnosis, but also for biomarker detection. The ideal biopsy specimen should meet two requirements, including more than 60 mm2 of tumor tissue and containing more than 20% of tumor cells. In order to obtain ideal lung cancer biopsy specimens, advanced imaging techniques are needed to help. In this article, we reviewed the requirements for biopsy specimens based on biomarker detection, as well as the current status and research progress of using imaging techniques for preoperative planning and intraoperative real time guidance of lung cancer biopsy.
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Perihematomal edema-based CT-radiomics model to predict functional outcome in patients with intracerebral hemorrhage.

PURPOSE: The purpose of this study was to identify possible association between noncontrast computed tomography (NCCT)-based radiomics features of perihematomal edema (PHE) and poor functional outcome at 90 days after intracerebral hemorrhage (ICH) and to develop a NCCT-based radiomics-clinical nomogram to predict 90-day functional outcomes in patients with ICH. MATERIALS AND METHODS: In this multicenter retrospective study, 107 radiomics features were extracted from 1098 NCCT examinations obtained in 1098 patients with ICH. There were 652 men and 446 women with a mean age of 60 ± 12 (SD) years (range: 23-95 years). After harmonized and univariable and multivariable screening, seven of these radiomics features were closely associated with the 90-day functional outcome of patients with ICH. The radiomics score (Rad-score) was calculated based on the seven radiomics features. A clinical-radiomics nomogram was developed and validated in three cohorts. The model performance was evaluated using area under the curve analysis and decision and calibration curves. RESULTS: Of the 1098 patients with ICH, 395 had a good outcome at 90 days. Hematoma hypodensity sign and intraventricular and subarachnoid hemorrhages were identified as risk factors for poor outcomes (P < 0.001). Age, Glasgow coma scale score, and Rad-score were independently associated with outcome. The clinical-radiomics nomogram showed good predictive performance with AUCs of 0.882 (95% CI: 0.859-0.905), 0.834 (95% CI: 0.776-0.891) and 0.905 (95% CI: 0.839-0.970) in the three cohorts and clinical applicability. CONCLUSION: NCCT-based radiomics features from PHE are highly correlated with outcome. When combined with Rad-score, radiomics features from PHE can improve the predictive performance for 90-day poor outcome in patients with ICH.

Role of iodine density value on dual-energy CT for detection of high tumor cell proportion region in lung cancer during CT-guided transthoracic biopsy.

OBJECTIVE: This study aimed to identify regions with at least 20% tumor cell content in lung cancer tumors by using spectral parameters from dual-layer spectral detector computed tomography (SDCT) to design the puncture path for transthoracic lung biopsy (TTLB). MATERIALS AND METHODS: This prospective study recruited patients with suspected lung cancer. Forty-one patients were enrolled to identify the high tumor cell proportion region (HTPR) and then another 15 patients to validate the accuracy of the HTPR. In each of the 41 patients, the suspected regions with high or low tumor cell proportions were punctured according to local iodine density (IoD) values for separate biopsies. The tumor cell proportions of 82 specimens were assessed and classified into high and low tumor cell proportions based on the threshold value of 20 %. The performance of spectral parameters was analyzed to distinguish the HTPR (tumor cell proportion ≥ 20 %) from the low tumor cell proportion region (LTPR). The cutoff value of optimal spectral parameter was used to prospectively guide the biopsy of the HTPR in 15 cases for further validation, and then the accuracy was calculated. RESULTS: The AUC values of spectral parameters were all higher than those of CTconventional in identifying the HTPR (all P < 0.05). The IoD with a cutoff value of 0.59 mg/mL in arterial phase (AP) yielded good performance (specificity: 97.10 %) in identifying the HTPR. It was applied to 15 cases for validation, and the accuracy rate was 100 %. CONCLUSION: Spectral CT parameters can be used to identify regions with at least 20% tumor cell content in lung cancer for biopsies.

Radiomics for prediction of intracerebral hemorrhage outcomes: A retrospective multicenter study.

BACKGROUND: Accurate risk stratification of patients with intracerebral hemorrhage (ICH) could help refine adjuvant therapy selection and better understand the clinical course. We aimed to evaluate the value of radiomics features from hematomal and perihematomal edema areas for prognosis prediction and to develop a model combining clinical and radiomic features for accurate outcome prediction of patients with ICH. METHODS: This multicenter study enrolled patients with ICH from January 2016 to November 2021. Their outcomes at 3 months were recorded based on the modified Rankin Scale (good, 0-3; poor, 4-6). Independent clinical and radiomic risk factors for poor outcome were identified through multivariate logistic regression analysis, and predictive models were developed. Model performance and clinical utility were evaluated in both internal and external cohorts. RESULTS: Among the 1098 ICH patients evaluated (mean age, 60 ± 13 years), 703 (64 %) had poor outcomes. Age, hemorrhage volume and location, and Glasgow Coma Scale (GCS) were independently associated with outcomes. The area under the receiver operating characteristic curve (AUC) of the clinical model was 0.881 in the external validation cohort. Addition of the Rad-score (combined hematoma and perihematomal edema area) improved predictive accuracy and model performance (AUC, 0.893), net reclassification improvement, 0.140 (P < 0.001), and integrated discrimination improvement, 0.050 (P < 0.001). CONCLUSIONS: The radiomics features of hematomal and perihematomal edema area have additional value in prognostic prediction; moreover, addition of radiomic features significantly improves model accuracy.

Development and Validation of a Clinical-Based Signature to Predict the 90-Day Functional Outcome for Spontaneous Intracerebral Hemorrhage.

We aimed to develop and validate an objective and easy-to-use model for identifying patients with spontaneous intracerebral hemorrhage (ICH) who have a poor 90-day prognosis. This three-center retrospective study included a large cohort of 1,122 patients with ICH who presented within 6 h of symptom onset [training cohort, n = 835; internal validation cohort, n = 201; external validation cohort (center 2 and 3), n = 86]. We collected the patients' baseline clinical, radiological, and laboratory data as well as the 90-day functional outcomes. Independent risk factors for prognosis were identified through univariate analysis and multivariate logistic regression analysis. A nomogram was developed to visualize the model results while a calibration curve was used to verify whether the predictive performance was satisfactorily consistent with the ideal curve. Finally, we used decision curves to assess the clinical utility of the model. At 90 days, 714 (63.6%) patients had a poor prognosis. Factors associated with prognosis included age, midline shift, intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), hypodensities, ICH volume, perihematomal edema (PHE) volume, temperature, systolic blood pressure, Glasgow Coma Scale (GCS) score, white blood cell (WBC), neutrophil, and neutrophil-lymphocyte ratio (NLR) (p < 0.05). Moreover, age, ICH volume, and GCS were identified as independent risk factors for prognosis. For identifying patients with poor prognosis, the model showed an area under the receiver operating characteristic curve of 0.874, 0.822, and 0.868 in the training cohort, internal validation, and external validation cohorts, respectively. The calibration curve revealed that the nomogram showed satisfactory calibration in the training and validation cohorts. Decision curve analysis showed the clinical utility of the nomogram. Taken together, the nomogram developed in this study could facilitate the individualized outcome prediction in patients with ICH.

[Clinical application of percutaneous spinal endoscopy debridement and lavage in sacroiliac joint tuberculosis].

OBJECTIVE: To investigate the feasibility and clinical efficacy of percutaneous spinal endoscopic debridement and lavage for the treatment of sacroiliac joint tuberculosis. METHODS: The clinical data of 7 patients with sacroiliac joint tuberculosis treated with percutaneous spinal endoscopic debridement and lavage from January 2007 to April 2009 were retrospectively analyzed. There were 2 males and 5 females, aged from 29 to 69 years old, 4 cases on the right side of the lesion and 3 cases on the left side. The course ranged from 8 to 144 months. According to Kim classification, 5 cases were type Ⅲ and 2 cases were type Ⅳ. All patients were treated with HRZE quadruple anti tuberculosis drugs for 2 to 6 weeks beforeoperation. VAS, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Oswestry Disability Index (ODI) were compared before and after surgery. RESULTS: All the operations were successful, the intraoperative blood loss was less than 50 ml on average, and no complications such as hematoma and infection were occurred. The follow-up time of 7 cases ranged from 18 to 40 months. Pain relief was obvious, and there was a statistical result in the VAS, ESR, and ODI of the patients at 1, 3, 6, 12, 18 months after operation compared with before treatment. At the final follow-up, the patient's clinical, imaging and laboratory examinations showed that the infection had disappeared, and the patient returned to normal life and work. CONCLUSION: Percutaneous spine endoscopic debridement and lavage has less tissue trauma, targeted operation, definite curative effects, and quick postoperative recovery, which has explored new options for minimally invasive treatment of sacroiliac joint tuberculosis.

Multi-Parametric Magnetic Resonance Imaging-Based Radiomics Analysis of Cervical Cancer for Preoperative Prediction of Lymphovascular Space Invasion.

BACKGROUND: Detection of lymphovascular space invasion (LVSI) in early cervical cancer (CC) is challenging. To date, no standard clinical markers or screening tests have been used to detect LVSI preoperatively. Therefore, non-invasive risk stratification tools are highly desirable. OBJECTIVE: To train and validate a multi-parametric magnetic resonance imaging (mpMRI)-based radiomics model to detect LVSI in patients with CC and investigate its potential as a complementary tool to enhance the efficiency of risk assessment strategies. MATERIALS AND METHODS: The model was developed from the tumor volume of interest (VOI) of 125 patients with CC. A total of 1037 radiomics features obtained from conventional magnetic resonance imaging (MRI), including a small field-of-view (sFOV) high-resolution (HR)-T2-weighted MRI (T2WI), apparent diffusion coefficient (ADC), T2WI, fat-suppressed (FS)-T2WI, as well as axial and sagittal contrast-enhanced T1-weighted MRI (T1c). We conducted a radiomics-based characterization of each tumor region using pretreatment image data. Feature selection was performed using the least absolute shrinkage and selection operator method on the training set. The predictive performance was compared with single variates (clinical data and single-layer radiomics signatures) analyzed using a receiver operating characteristic (ROC) curve. Three-fold cross-validation performed 20 times was used to evaluate the accuracy of the trained classifiers and the stability of the selected features. The models were validated by using a validation set. RESULTS: Feature selection extracted the six most important features (3 from sFOV HR-T2WI, 1 T2WI, 1 FS-T2WI, and 1 T1c) for model construction. The mpMRI-combined radiomics model (area under the curve [AUC]: 0.940) reached a significantly higher performance (better than the clinical parameters [AUC: 0.730]), including any single-layer model using sFOV HR-T2WI (AUC: 0.840), T2WI (AUC: 0.770), FS-T2WI (AUC: 0.710), ADC maps (AUC: 0.650), sagittal, and axial T1c values (AUC: 0.710, 0.680) in the validation set. CONCLUSION: Biomarkers using multi-parametric radiomics features derived from preoperative MR images could predict LVSI in patients with CC.

Targeting PRMT5/Akt signalling axis prevents human lung cancer cell growth.

The emerging evidence reveals that protein arginine methyltransferase 5 (PRMT5) is involved in regulation of tumour cell proliferation and cancer development. Nevertheless, the exact role of PRMT5 in human lung cancer cell proliferation and the underlying molecular mechanism remains largely obscure. Here, we showed that PRMT5 was highly expressed in human lung cancer cells and lung cancer tissues. Furthermore, we generated PRMT5 stable knockdown cell lines (A549 and H1299 cells) and explored the functions of PRMT5 in lung cancer cell proliferation. We found that the down-regulation of PRMT5 by shRNA or the inhibition of PRMT5 by specific inhibitor GSK591 dramatically suppressed cyclin E1 and cyclin D1 expression and cell proliferation. Moreover, we uncovered that PRMT5 promoted lung cancer cell proliferation via regulation of Akt activation. PRMT5 was directly co-localized and interacted with Akt, but not PTEN and mTOR. Down-regulation or inhibition of PRMT5 markedly reduced Akt phosphorylation at Thr308 and Ser473, whereas the expression of PTEN and mTOR phosphorylation was unchanged, indicating that PRMT5 was an important upstream regulator of Akt and induced lung cancer cell proliferation. Altogether, our results indicate that PRMT5 promotes human lung cancer cell proliferation through direct interaction with Akt and regulation of Akt activity. Our findings also suggest that targeting PRMT5 may have therapeutic potential for treatment of human lung cancer.

Inhalation lung injury induced by smoke bombs in children: CT manifestations, dynamic evolution features and quantitative analysis.

BACKGROUND: This retrospective study aimed to investigate the computed tomography (CT) manifestations, short-term dynamic evolution features and quantitative lung CT analysis of inhalation lung injury induced by smoke bomb flare. METHODS: Eleven pediatric patients (aged 11 to 13) who inhaled the smoke of smoke bombs underwent several low-dose chest CT scans. The image characteristics and their dynamic changes were observed and quantitative CT values were analyzed. The quantitative CT indicators included lung injury CT score (LICTS), lung fibrosis CT score (LFCTS), mean lung density (MLD), normally aerated volume ratio (NAVR) and reductively aerated volume ratio (RAVR). Box-plot was used to analyze the dynamic changes of each indicator and Spearman statistical method was used to analyze the correlation between any two indicators. RESULTS: (I) In most cases, there were multiple consolidation and massive ground-glass opacities (GGOs) in the two lungs, which aggravated in the early stage and then gradually dissoluted in the later stage. LICTS was positively correlated with MLD (r=0.811, P=0.000), while it was negatively correlated with NAVR (r=-0.712, P=0.000). There existed interstitial fibrosis in the later stage, and LFCTS was positively correlated with RAVR (r=0.382, P=0.028). (II) In one case, the patterns were like layered cake, i.e., consolidation with air bronchus signs in the accumulation area, GGOs in the aforementioned area and normal lung in the top area. The patterns aggravated in the early stage and quickly dissolved in the later stage, and only a few residual fibrotic lesions existed on the final scan. (III) For severe cases, pneumomediastinum and subcutaneous emphysema aggravated in the early stage and then gradually dissolved in the later stage. CONCLUSIONS: The chest CT manifestations of inhalation lung injury induced by smoke bombs are predominantly GGOs and consolidation. They aggravate in the early stage and gradual dissolute in the later stage. CT quantitative values can contribute to evaluating the extent of this disease, and NAVR and RAVR can be used to assess pulmonary function.

Comparison of Image Quality, Diagnostic Accuracy and Radiation Dose Between Flash Model and Retrospective ECG-Triggered Protocols in Dual Source Computed Tomography (DSCT) in Congenital Heart Diseases.

BACKGROUND: Dual source computed tomography (DSCT) plays an important role in the diagnosis of congenital heart diseases (CHD). However, the issue of radiation-related side effects constitutes a wide public concern. The aim of the study was to explore the differences in diagnostic accuracy, radiation dose and image quality between a prospectively ECG - triggered high - pitch spiral acquisition (flash model) and a retrospective ECG-gated protocol of DSCT used for the detection of CHD. MATERIAL/METHODS: The study included 58 patients with CHD who underwent a DSCT examination, including two groups of 29 patients in each protocol. Then, both subjective and objective image quality, diagnostic accuracy and radiation dose were compared between the two protocols. RESULTS: The image quality and the total as well as partial diagnostic accuracy did not differ significantly between the protocols. The radiation dose in the flash model was obviously lower than that in the retrospective model (P<0.05). CONCLUSIONS: Compared to the retrospective protocol, the flash model can significantly reduce the dose of radiation, while maintaining both diagnostic accuracy and image quality.

Therapeutic effects of C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me; bardoxolone methyl) on radiation-induced lung inflammation and fibrosis in mice.

The C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me), one of the synthetic triterpenoids, has been found to have potent anti-inflammatory and anticancer properties in vitro and in vivo. However, its usefulness in mitigating radiation-induced lung injury (RILI), including radiation-induced lung inflammation and fibrosis, has not been tested. The aim of this study was to explore the therapeutic effect of CDDO-Me on RILI in mice and the underlying mechanisms. Herein, we found that administration of CDDO-Me improved the histopathological score, reduced the number of inflammatory cells and concentrations of total protein in bronchoalveolar lavage fluid, suppressed secretion and expression of proinflammatory cytokines, including transforming growth factor-ß and interleukin-6, elevated expression of the anti-inflammatory cytokine interleukin-10, and downregulated the mRNA level of profibrotic genes, including for fibronectin, α-smooth muscle actin, and collagen I. CDDO-Me attenuated radiation-induced lung inflammation. CDDO-Me also decreased the Masson's trichrome stain score, hydroxyproline content, and mRNA level of profibrotic genes, and blocked radiation-induced collagen accumulation and fibrosis. Collectively, these findings suggest that CDDO-Me ameliorates radiation-induced lung inflammation and fibrosis, and this synthetic triterpenoid is a promising novel therapeutic agent for RILI. Further mechanistic, efficacy, and safety studies are warranted to elucidate the role of CDDO-Me in the management of RILI.

[Advanced oxidation protein products induce epithelial-to-mesenchymal transition in cultured human proximal tubular epithelial cells via oxidative stress].

OBJECTIVE: To investigate the effects of advanced oxidation protein products (AOPP) on epithelial-to-mesenchymal transition (EMT) in cultured human proximal tubular epithelial cells (HK-2) and explore the mechanism. METHODS: HK-2 cells treated with 50, 100, 200, and 400 µg/ml AOPP or 50 µg/m bovine serum albumin (BSA) for 24 h, or with 200 µg/ml AOPP for 0.5, 1, 3, 6, 12, and 24 h were examined for the protein expression of α-SMA and E-cadherin. In cells pretreated with diphenyleneiodonium (DPI) or cytoplasmic superoxide dismutase (C-SOD), the effects of 50 µg/ml BSA and 200 µg/ml AOPP were assessed on the expressions of α-SMA and E-cadherin, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, catalase (CAT) activity, and glutathione peroxidase (GSH-px) activity. RESULTS: AOPP treatment up-regulated α-SMA expression and down-regulated E-cadherin expression in a dose- and time-dependent fashion. AOPP exposure of the cells resulted in increased MDA level and lowered activities of SOD, CAT and GSH-PX. DPI and C-SOD partially attenuated the effects of AOPP on α-SMA, E-cadherin, MDA, SOD, CAT and GSH-px. CONCLUSION: AOPP can induce EMT in cultured HK-2 cells via oxidative stress, and this effect can be attenuated by inhibiting the activation of NADPH oxidase and using antioxidants to delay the progression of renal interstitial fibrosis.

[Correlation between TMEM39A gene polymorphism and systemic lupus erythematosus in Chinese Han patients].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) of the transmembrane protein 39A (TMEM39A) at the loci 1880G/A, 2442T/G, and 2456A/T and systemic lupus erythematosus (SLE) in Chinese Han patients. METHODS: TMEM39A gene polymorphisms at 3 loci (1880G/A, 2442T/G, 2456 A/T) were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 110 Chinese Han patients with SLE and 80 normal control subjects, and the allele and genotype frequencies were compared by Chi-square test between the two groups. RESULTS: Both the genotype frequencies (AA, GA and GG) and allele frequencies (A and G) at 1880G/A differed significantly between SLE cases and the normal controls (P=0.002 and P=0.044, respectively). The two groups also showed significant differences in the genotype frequencies (GG, TG and TT) (P=0.001) and allele frequencies (G and T) (P=0.041) at 2442T/G. No significant differences were found in the genotype frequencies (TT, AT and AA) or allele frequencies (T and A) at 2456A/T between the two groups (P>0.05). The allele and genotype frequencies of the 3 SNPs showed no significant differences between lupus nephritis (LN) patients and non-LN patients. CONCLUSION: The TMEM39A polymorphisms at 1880G/A and 2442T/G, but not at 2456 A/T gene, may be associated with the susceptibility to SLE in Chinese Han population. The genotype or allele frequencies of the 3 SNPs have no effect on the incidence of lupus nephritis.

Biological evaluation and molecular modelling study of podophyllotoxin derivatives as potent inhibitors of tubulin polymerization.

Microtubules are considered as important targets of anticancer therapy. Podophyllotoxin and its structural derivative are major microtubule-interfering agents with potent anticancer activity. In this study, we reported the anticancer effects of 10 representative podophyllotoxin derivatives on a panel of four human cancer cell lines. Deoxypodophyllotoxin (6b) and ß-apopicropodophyllotoxin (6g) elicited strong antiproliferative effects (IC50) at a range of 0.0073-0.14 µM. Direct tubulin depolymerization assay in vitro was also performed. Results showed that that the two compounds can inhibit microtubule polymerization. Experimental measurements were also supported by molecular dynamic simulations, which showed that the two active compounds formed interactions with the colchicine-binding site of the tubulin protein. Our results helped us understand the nature of tubulin binding and determine the core design of a new series of potent inhibitors of tubulin polymerization.

Molecular interaction of PCB153 to human serum albumin: insights from spectroscopic and molecular modeling studies.

Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

Synthesis and biological evaluation of a series of podophyllotoxins derivatives as a class of potent antitubulin agents.

A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (K562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs.

Proteomic analysis of the effect of triterpenes from Patrinia heterophylla on leukemia K562 cells.

For centuries, Patrinia heterophylla had been used in China to treat many diseases including tumor. Triterpenes has been identified as the major active constituents in Patrinia heterophylla. To elucidate the antitumor mechanism of triterpenes from Patrinia heterophylla1 (TPH), a proteomic analysis is carried out with TPH treatment in K562 cells. The total proteins extracted from TPH treated K562 cells are analyzed by two dimensional gel electrophoresis (2-DE) and compared with those untreated K562 cells. Mass spectrometry is applied to identify the differentially expressed proteins. Twenty-three differentially expressed significant proteins are discovered. Eight proteins are later identified by mass spectrometry (MALDI-TOF-MS) and Mascot software. Among them, four proteins are up-regulated (Aldolase A, Glyceraldehyde-3-phosphate dehydrogenase, Flavin reductase and Hemoglobin subunit) and four proteins were down-regulated (Heat-shock protein 90 〈Alpha〉 (HSP90-〈Alpha〉), Eukaryotic translation initiation factor 5A, Moesin, tublin) by TPH treatment in K562 cells. The identified proteins are associated with energy metabolism, oxidative stress, apoptosis, signal transduction, differential induction, and protein biosynthesis. These findings might provide valuable insights into the antitumor mechanism of TPH in K562 cells.