Performance of ATT and UDFF in the diagnosis of non-alcoholic fatty liver: An animal experiment.

Objective: To establish a Bama minipigs model with Non-Alcoholic Fatty Liver (NAFL) induced by a high-fat diet and investigate the application of attenuation coefficient (ATT) and ultrasound-derived fat fraction (UDFF) in the diagnosis of NAFL. Methods: Six-month-old male Bama minipigs were randomly divided into normal control and high-fat groups (n = 3 pigs per group), and fed with a control diet and high-fat diet for 32 weeks. Weight and body length were measured every four weeks, followed by quantitative ultrasound imaging (ATT and UDFF), blood biochemical markers, and liver biopsies on the same day. Using the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) as a reference, we analyzed the correlation between ATT, UDFF, and their score results. Results: Compared with the normal control group, the body weight, body mass index (BMI), and serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the High-fat group were significantly different at Week 12 (P < 0.05). Spearman correlation analysis showed that the ATT value was significantly correlated with NAS score (r = 0.76, P < 0.001), and the UDFF value was significantly correlated with NAS score (r = 0.80, P < 0.001). The optimal cut-off value of ATT and UDFF were 0.59 dB/cm/MHz and 5.5%, respectively. These values are optimal for diagnosis of NAFL in Bama minipig model. Conclusion: ATT and UDFF have a high correlation with steatosis, and can be used as a non-invasive method for early screening of hepatic steatosis, which can dynamically monitor the change of disease course.

Theoretical Prediction on Properties of 3,4-Bisnitrofurazanfuroxan (DNTF) Crystal and its Polymer Bonded Explosives (PBXs) Through Molecular Dynamics (MD) Simulation.

CONTEXT: 3,4-Bisnitrofurazanfuroxan (DNTF) is a typical high energy density compound (HEDC), it has high crystal density and detonation parameters, but also high mechanical sensitivity. To decrease its mechanical sensitivity, the DNTF based polymer bonded explosives (PBXs) was designed. The pure DNTF crystal and PBXs models were established. The stability, sensitivity, detonation performance and mechanical properties of DNTF crystal and PBXs models were predicted. Results show that PBXs models containing fluorine rubber (F2311) and fluorine resin (F2314) have higher binding energy, meaning that DNTF/F2311 and DNTF/F2314 is relatively more stable. PBXs models have higher value of cohesive energy density (CED) than pure DNTF crystal, DNTF/F2311 and DNTF/F2314 have the highest value of CED, implying that the sensitivity of PBXs is effectively decreased, DNTF/F2311 and DNTF/F2314 is more insensitive. PBXs have lower crystal density and detonation parameters than DNTF, the energy density is declined, DNTF/F2314 has higher energetic performance than other PBXs. Compared with pure DNTF crystal, engineering moduli (tensile modulus, shear modulus, bulk modulus) of PBXs models are obviously decreased, but Cauchy pressure is increased, implying that the mechanical properties of PBXs is superior to pure DNTF component, the PBXs containing F2311 or F2314 have more preferable mechanical properties. Consequently, DNTF/F2311 and DNTF/F2314 have the best comprehensive properties and is more attractive among the designed PBXs, indicating that F2311 and F2314 are more advantageous and promising in ameliorating properties of DNTF. METHODS: The properties of DNTF crystal and PBXs models were predicted through molecular dynamics (MD) method under Materials Studio 7.0 package. The MD simulation was performed with isothermal-constant volume (NVT) ensemble, and the force field was chosen as COMPASS force field. The temperature was set as 295 K, the time step was 1 fs and the total MD simulation time was 2 ns.

Head-to-head comparison of perfluorobutane contrast-enhanced US and multiparametric MRI for breast cancer: a prospective, multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency. PATIENTS AND METHODS: This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions. RESULTS: In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online. CONCLUSIONS: PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

Designing and property prediction of a novel three-component CL-20/HMX/TNAD energetic cocrystal explosive by MD method.

CONTEXT: Cocrystallization technology can effectively regulate crystal structure, alter packing mode, and improve physicochemical performances of energetic materials at molecule level. CL-20/HMX cocrystal explosive has high energy density than HMX, but it also exhibits high mechanical sensitivity. To decrease the sensitivity and improve the properties of CL-20/HMX energetic cocrystal, the three-component energetic cocrystal CL-20/HMX/TNAD was designed. The properties of CL-20, CL-20/HMX, and CL-20/HMX/TNAD cocrystal models were predicted. The results show that CL-20/HMX/TNAD cocrystal models have better mechanical properties than CL-20/HMX cocrystal model, implying that the mechanical properties can be effectively improved. The binding energy of CL-20/HMX/TNAD cocrystal models is higher than CL-20/HMX cocrystal model, indicating that the three-component energetic cocrystal is more stable, and the cocrystal model with the ratio 3:4:1 is predicted to be the most stable phase. CL-20/HMX/TNAD cocrystal models have higher value of trigger bond energy than pure CL-20 and CL-20/HMX cocrystal models, meaning that the three-component energetic cocrystal is more insensitive. The crystal density and detonation parameters of CL-20/HMX and CL-20/HMX/TNAD cocrystal models are lower than CL-20, illustrating that the energy density is declined. The CL-20/HMX/TNAD cocrystal has higher energy density than RDX and can be regarded as a potential high energy explosive. METHODS: This paper was performed with molecular dynamics (MD) method with the software of Materials Studio 7.0 under COMPASS force field. The MD simulation was performed under isothermal-isobaric (NPT) ensemble, the temperature and pressure was 295 K and 0.0001 GPa, respectively.

Theoretical research on performances of CL-20/HMX cocrystal explosive and its based polymer bonded explosives (PBXs) by molecular dynamics method.

In this article, the CL-20/HMX cocrystal model was established and its based polymer bonded explosives (PBXs) were designed. The static performances, including mechanical properties, stability and detonation performance of CL-20/HMX cocrystal model and PBXs models, were predicted by molecular dynamics (MD) method. The mechanical parameters, binding energy, and detonation parameters of PBXs models were calculated and compared with that of pure CL-20/HMX cocrystal model. The influence of polymer binders on performances of CL-20/HMX cocrystal explosive was evaluated. Results show that the polymer binders make the engineering moduli (tensile modulus, shear modulus, and bulk modulus) of PBXs declined and Cauchy pressure increased, meaning that the polymer binder can obviously improve mechanical properties of CL-20/HMX cocrystal explosive, and the PBXs model with fluorine rubber (F2311) has the best mechanical properties. In different PBXs models, the binding energy between CL-20, HMX molecules and F2311 is higher than other polymer binders, indicating that the CL-20/HMX/F2311 model is more stable. The PBXs models have lower value of crystal density and detonation parameters compared with pure CL-20/HMX cocrystal and the energetic performance of PBXs is weakened. The PBXs model with fluorine resin (F2314) has the highest energetic performance and it is higher than pure HMX. Therefore, the CL-20/HMX/F2311 and CL-20/HMX/F2314 models have more favorable comprehensive properties, proving that F2311 and F2314 are more preferable and promising to design CL-20/HMX cocrystal based PBXs.

Study on Multi-Layer Filling Treatment of Extra-Large Goaf and Its Underground Application.

At present, the many domestic, large mined-out areas caused by single filling ability of the slurry flow state, thin layer flow and hardening after filling in multilayer structure generally need to finish filling for many times, because after a filling experience shows that filling body in the last solidification of flow, this leads to a lower one side of the roof, and far distance part of the filling body cannot pick up top. The determination of backfill strength is the key problem of the cemented backfill method, and it is affected by many factors. Therefore, through theoretical calculation, laboratory testing and numerical simulation methods, combined with the field filling process, this paper has verified the flow accumulation and stratification characteristics of stope layered filling slurry. When the slurry concentration is 60−73%, the slope increases exponentially from 2.5° to 8°. It is revealed that the delamination and meshing state are the key factors to determine the overall strength of large-scale stope filling through the testing of particle size distribution in interlayer and flow direction. The reduction effect of the number and Angle of structural weak surface formed by layering and filling on strength is revealed: cement−sand ratio 1:12, concentration 68%, standard curing R28 > 1.81 MPa. The strength reduction coefficient is 61.31% and 92.96% when the number of layers is 1−4. The higher the number of layers, the greater is the reduction coefficient, and when the stratification angle increases by 2, the strength of backfill decreases by 20−30%. The verification of stope filling coring shows that the in situ strength reaches 2.42 MPa, which is 0.61 MPa higher than the standard curing strength, with an increase of 33.7%. When the depth is from 1 m to 5 m, the strength increases from 2.26 MPa to 2.69 MPa, with an increase rate of 18.2%. Finally, through the research and application of the comprehensive technology of mining and filling coordination under the complex goaf group, the residual ore resources of Xianglushan tungsten mine are effectively recovered, the volume of goaf is significantly reduced, and the safety of goaf is improved.

Highly sensitive fluorescent detection of EDIL3 overexpressed exosomes for the diagnosis of triple-negative breast cancer.

EDIL3 is a strong and highly accurate diagnostic marker for breast cancer, meanwhile, EDIL3 overexpressed exosomes are novel biomarkers for the early diagnosis of triple-negative breast cancer (TNBC). Here, we proposed a fluorescent detection method for EDIL3 overexpressed exosomes, which is simple and sensitive. Basically, we utilized a magnetic nanospheres (MNS) based liquid sandwich immunoassay strategy. MNS were modified with CD63 aptamers, which can immunologically bound to the CD63 protein on the surface of exosomes. Alexa Fluor 647 labeled anti-EDIL3 antibodies (Anti-EDIL3/AF647) were used as the fluorescent probes to recognize the EDIL3 on exosomes derived from a TNBC cell line (MDA-MB-231). With the target TNBC exosomes present, sandwich structures containing MNS, exosomes and fluorescent probes were formed. After magnetic purification, optical super resolution imaging of the products was conducted to check the specificity of the assay. In addition, fluorescence signals of the products were detected to quantitatively analyze the EDIL3 overexpressed exosomes. The linear range was found to be 7.78 × 101to 7.78× 106particlesµl-1. The detection limit was approximately 10 particlesµl-1. The feasibility of the method for the detection of exosomes in complex biological samples was also demonstrated. Such a simple and sensitive detection method for EDIL3 overexpressed exosomes holds a great potential in clinical diagnosis of TNBC.

Real-World Prescription Patterns For Patients With Young-Onset Parkinson's Disease in China: A Trend Analysis From 2014 to 2019.

Introduction Pharmacotherapy is one of the main treatments for patients with young-onset Parkinson's disease (YOPD). Although numerous studies on the treatment of YOPD have been published, the real-world prescription patterns of these populations remain unclear in China. Methods A national comprehensive evaluation was performed to reveal the pharmacological treatment patterns in Chinese patients with Parkinson's disease from 1 January 2014 to 31 December 2019, with patients aged 21-50 years classified as having YOPD for the subgroup analysis. Information on patients and drugs was extracted to analyse the demographic characteristics, prescription patterns, and levodopa equivalent daily dose (LED) during disease progression. Results A total of 1,134 patients with YOPD were included, and the majority were aged 41-50 years. Prescription of L-DOPA/benserazide and pramipexole accounted for more than 30 and 20%, respectively, in each year from 2014 to 2019. There was no difference in prescription patterns in terms of age, sex and geographical areas. Half of the patients with YOPD were on monotherapy, but the proportion decreased from 2016. Correspondingly, the proportion of patients receiving polytherapy increased, especially those who were prescribed more than two anti-Parkinson's disease drugs. During the disease course, LED showed high variability, which increased over time. Conclusion L-DOPA/benserazide and pramipexole were the most frequently prescribed anti-PD drugs for patients with YOPD in China. There was a slight trend in the transition from monotherapy to polytherapy. LED increased with disease duration. Thus, we provided an overview of the prescription patterns for patients with YOPD in China.

Theoretical investigations on stability, sensitivity, energetic performance, and mechanical properties of CL-20/TNAD cocrystal explosive by molecular dynamics method.

The crystal models of trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin (TNAD), hexanitrohexaazaisowurtzitane (CL-20), and CL-20/TNAD cocrystal explosive with different component ratios were established. Molecular dynamics (MD) method was applied to predict the stability, sensitivity, energetic properties, and mechanical properties. The effect of component ratio on properties of CL-20/TNAD cocrystal explosive was investigated and estimated. Results show that the cocrystal model with component ratio in 1:1 exhibits the highest binding energy and it is more stable. In CL-20/TNAD cocrystal explosive, the interaction energy of trigger bond is increased by 0.8 ~ 15.0 kJ/mol, implying that the mechanical sensitivity of CL-20/TNAD cocrystal explosive is lower than CL-20 and the safety is effectively improved. Compared with raw CL-20, the crystal density of cocrystal explosive is declined by 0.014 ~ 0.193 g/cm3, detonation velocity is declined by 39 ~ 755 m/s, and detonation pressure is declined by 0.95 ~ 11.40 GPa; namely the energy density of CL-20/TNAD cocrystal explosive is lower than CL-20. The cocrystal explosives with component ratio in 10:1 ~ 1:1 still exhibit desirable detonation performance and can be regarded as high energy density explosives. The values of tensile modulus, shear modulus, and bulk modulus of CL-20/TNAD cocrystal explosive are decreased by 0.448 ~ 10.285 GPa, 0.195 ~ 4.189 GPa, and 0.194 ~ 6.292 GPa, respectively, Cauchy pressure is increased by 0.990 ~ 5.704 GPa, meaning that the rigidity, fracture strength, and hardness of cocrystal explosive are declined, while the plastic property and ductility are increased and the mechanical properties are improved. The cocrystal model with component ratio in 1:1 has the best mechanical properties. Consequently, the CL-20/TNAD cocrystal explosive with component ratio in 1:1 is more stable and insensitive; it also has high energy density and the best mechanical properties and may be an attractive candidate for high energy explosives.

Evaluation of gastric emptying in patients with gastroparesis by three-dimensional ultrasound.

BACKGROUND: To diagnose gastroparesis, it is necessary to assess gastric emptying accurately. This study aims to investigate the role of three-dimensional ultrasonography (3-D US) on the measurement of gastric volume to evaluate gastric accommodation in healthy patients. METHODS: In this study, 21 volunteers, 46 patients with diabetic gastroparesis (DG), and 22 patients with postsurgical gastroparesis (PSG) underwent 3-D US after oral administration of 250 mL gastrointestinal contrast at 2, 30, 60, and 90 min. The volume of the contrast agent in the stomach was then calculated using the virtual organ computer-aided analysis (VOCAL) (Virtual Organ Computer-aided AnaLysis, General Electric Medical Systems, Kretztechnik, Zipf, Austria). RESULTS: In the DG group, the gastric residue volumes at postprandial 60 and 90 min were significantly higher than those in the healthy group (P<0.05), and the areas under the receiver operating characteristic (ROC) curve of these parameters were 0.830 and 0.957, respectively. There were significant differences between the PSG and healthy groups at 60 and 90 min; however, the AUC of gastric residue at 90 min (0.955) was higher than the AUC at 60 min (0.697). CONCLUSIONS: Therefore, this study showed that the 3-D US is a powerful tool for assessing gastric emptying and provides a new strategy for diagnosing gastroparesis.

Differential diagnosis between small breast phyllodes tumors and fibroadenomas using artificial intelligence and ultrasound data.

BACKGROUND: It is challenging to differentiate between phyllodes tumors (PTs) and fibroadenomas (FAs). Artificial intelligence (AI) can provide quantitative information regarding the morphology and textural features of lesions. This study attempted to use AI to evaluate the ultrasonic images of PTs and FAs and to explore the diagnostic performance of AI features in the differential diagnosis of PTs and FAs. METHODS: A total of 40 PTs and 290 FAs <5 cm in maximum diameter found in female patients were retrospectively analyzed. All tumors were segmented by doctors, and the features of the lesions were collated, including circularity, height-to-width ratio, margin spicules, margin coarseness (MC), margin indistinctness, margin lobulation (ML), internal calcification, angle between the long axis of the lesion and skin, energy, grey entropy, and grey mean. The differences between PTs and FAs were analyzed, and the diagnostic performance of AI features in the differential diagnosis of PTs and FAs was evaluated. RESULTS: Statistically significant differences (P<0.05) were found in the height-to-width ratio, ML, energy, and grey entropy between the PTs and FAs. Receiver operating characteristic (ROC) curve analysis of single features showed that the area under the curve [(AUC) 0.759] of grey entropy was the largest among the four features with statistically significant differences, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.925, 0.459, 0.978, and 0.190, respectively. When considering the combinations of the features, the combination of height-to-width ratio, margin indistinctness, ML, energy, grey entropy, and internal calcification was the most optimal of the combinations of features with an AUC of 0.868, and a sensitivity, specificity, PPV, and NPV of 0.734, 0.900, 0.982, and 0.316, respectively. CONCLUSIONS: Quantitative analysis of AI can identify subtle differences in the morphology and textural features between small PTs and FAs. Comprehensive consideration of multiple features is important for the differential diagnosis of PTs and FAs.

Clinical value of contrast-enhanced ultrasound for the differential diagnosis of specific subtypes of uterine leiomyomas.

OBJECTIVE: To improve the accuracy of clinical diagnosis by analyzing different contrast-enhanced ultrasound (CEUS) imagines of specific subtypes of uterine leiomyomas. METHODS: A total of 147 female patients received preoperative CEUS examination. The scanning plane of the biggest tumors for CEUS was found by common B-mode ultrasonographic scanning on pelvic cavity, then 1.5 mL SonoVue were injected into the median cubital vein. According to the CEUS images, the lesion enhanced time, enhanced level and enhanced morphology were recorded. The time-intensity curve was acquired and analyzed, meanwhile, the relevant parameters were calculated, including rise time (RT), peak intensity (PI), time to peak (TTP) and mean transit time (MTT). RESULTS: In cellular uterine leiomyoma group, the percentage of high enhancement, early enhancement was higher, equal enhancement and synchronic enhancement were lower than those in the common uterine leiomyomas group. In hysteromyoma with hyaline degeneration group, the percentage of high enhancement, early enhancement was lower, while low enhancement and delayed enhancement were higher than those in the common uterine leiomyomas group. The ratio of PI in cellular uterine leiomyoma group was the highest, but the ratios of RT, TTP and MTT were the lowest of the three benign groups. The ratio of PI in hysteromyoma with hyaline degeneration group was the lowest, while the ratios of RT and TTP was the highest among the three benign groups. CONCLUSION: Different pathological types of uterine leiomyomas have their own signal performance on CEUS. CEUS can be used to infer their pathological types and help differential diagnosis.

Application of ultrasound artificial intelligence in the differential diagnosis between benign and malignant breast lesions of BI-RADS 4A.

BACKGROUND: The classification of Breast Imaging Reporting and Data System 4A (BI-RADS 4A) lesions is mostly based on the personal experience of doctors and lacks specific and clear classification standards. The development of artificial intelligence (AI) provides a new method for BI-RADS categorisation. We analysed the ultrasonic morphological and texture characteristics of BI-RADS 4A benign and malignant lesions using AI, and these ultrasonic characteristics of BI-RADS 4A benign and malignant lesions were compared to examine the value of AI in the differential diagnosis of BI-RADS 4A benign and malignant lesions. METHODS: A total of 206 lesions of BI-RADS 4A examined using ultrasonography were analysed retrospectively, including 174 benign lesions and 32 malignant lesions. All of the lesions were contoured manually, and the ultrasonic morphological and texture features of the lesions, such as circularity, height-to-width ratio, margin spicules, margin coarseness, margin indistinctness, margin lobulation, energy, entropy, grey mean, internal calcification and angle between the long axis of the lesion and skin, were calculated using grey level gradient co-occurrence matrix analysis. Differences between benign and malignant lesions of BI-RADS 4A were analysed. RESULTS: Significant differences in margin lobulation, entropy, internal calcification and ALS were noted between the benign group and malignant group (P = 0.013, 0.045, 0.045, and 0.002, respectively). The malignant group had more margin lobulations and lower entropy compared with the benign group, and the benign group had more internal calcifications and a greater angle between the long axis of the lesion and skin compared with the malignant group. No significant differences in circularity, height-to-width ratio, margin spicules, margin coarseness, margin indistinctness, energy, and grey mean were noted between benign and malignant lesions. CONCLUSIONS: Compared with the naked eye, AI can reveal more subtle differences between benign and malignant BI-RADS 4A lesions. These results remind us carefully observation of the margin and the internal echo is of great significance. With the help of morphological and texture information provided by AI, doctors can make a more accurate judgment on such atypical benign and malignant lesions.

Protective effects of rapamycin induced autophagy on CLP septic mice.

Sepsis is a life-threatening condition that may develop to multiple organ failure and septic shock. Autophagy is considered to play an important role in the regulation of inflammation. The present study aims to investigate the protective role of mTORC1 inhibitor, rapamycin, on septic death using cecal ligation and puncture (CLP) mice model. Here, results showed that pretreatment with rapamycin reduced the pyroptosis of peritoneal macrophages stimulated by cecal contents and the release of inflammatory factors such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α); In septic mice, rapamycin treatment decreased the activation of inflammasome in lung, and alleviated the pathological injuries in lung, liver and spleen tissues during acute stage of sepsis. Treatment of rapamycin rescued animals from septic death significantly. Our results indicated that activation of autophagy is a potential strategy to regulate the excessive inflammation in acute stage of sepsis.

Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line.

AIM: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line. METHODS: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using the 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. RESULTS: Oridonin suppressed the proliferation of the HeLa cell line in a dose- and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate- ribose polymerase cleavage. In addition, Z-D(OMe)-E(OMe)-V-D(OMe)- FMK (z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein. CONCLUSION: Our results showed that oridonin-induced apoptosis involved several molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.