Prospective assessment of pancreatic ductal adenocarcinoma diagnosis from endoscopic ultrasonography images with the assistance of deep learning.

BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.

Preparation of dopamine-modified sea squirt cellulose hydrogel dust-fixing agent to prevent raising of dust.

Sea squirts, a tunicate, are found in all oceans and can foul marine ports and aquaculture, mainly affecting shipping and biodiversity. In this study, cellulose was extracted from sea squirts, and its hydrophilic properties were improved by substituting the hydrogen ions of the cellulose -OH with dopamine. The modified cellulose was used to prepare a hydrogel for use as a dust-fixing agent (CDP) to reduce air pollution caused by dust. After response surface method optimization, the proportions of binder, water-retaining agent, wetting agent, and antifreeze in CDP were 0.97, 1.44, 0.23, and 6.32%, respectively. This composition improved the wetting ability and permeability of CDP on particle surfaces. CDP exhibited good water retention at -11-50 °C. CDP reduced the wind erosion rate of dust at a wind speed of 12 m/s to 1.18%. The molecular dynamics method was used to analyze the wetting process and mechanism of CDP, revealing that hydrogen bonds were the dominant force at the solid-liquid interface. The adsorption of CDP onto the surface of coal increased the number of hydrophilic points. Water molecules were adsorbed on these hydrophilic points through hydrogen bonding, improving the binding energy between the solid and liquid interfaces. The application of ascidian cellulose in dust control makes full use of the biological value of ascidians, promoting sustainable development of the global biological economy.

Diagnostic Value of Qualitative and Quantitative Contrast-Enhanced Ultrasound for Pathological Subtypes of Small Solid Renal Masses.

OBJECTIVES: To assess the diagnostic value of qualitative and quantitative contrast-enhanced ultrasound (CEUS) for pathological subtypes of small solid renal masses (sSRMs). METHODS: Patients with sSRMs confirmed by surgical pathology from January 2019 to November 2021 were retrospectively identified. All patients were divided into 3 groups: clear cell renal cell carcinoma (ccRCC) group, none-ccRCC group (renal cell carcinoma other than ccRCC), and angiomyolipoma (AML) group. The mass position, size, echogenicity and blood flow signals were compared. The speed of wash-in, wash-out, the degree of peak enhancement and the homogeneity at peak enhancement, the presence of pseudocapsule sign in CEUS imaging were qualitatively evaluated. Peak enhancement, wash-in area under the curve (WiAUC), rise time, time to peak, wash-in rate (WiR), wash-in perfusion index (WiPI) and tumor-to-cortex enhancement ratio of the above parameters in CEUS imaging were quantitatively evaluated. RESULTS: Of 105 patients, 105 sSRMs (66 ccRCC, 18 none-ccRCC, 21 AML) were enrolled in this study. No significant differences were found on location, size and echogenicity among 3 groups (all P > .05). The proportion of fast-washout and hypo-enhancement were highest in none-ccRCC group. Heterogeneous enhancement was detected in 87.88% in ccRCC group which is significantly higher than other 2 groups. Hundred percent of the AML showed no pseudocapsule sign, which is the highest among the 3 groups. Peak enhancement, WiAUC, WiR, WiPI of ccRCC group were the highest among the 3 groups. CONCLUSIONS: Qualitative and quantitative CEUS not only has the diagnostic value in distinguishing AML from malignant sSRMs, but also helps to differentiate the pathological subtypes of sSRMs.

Comparison Between SonoVue and Sonazoid Contrast-Enhanced Ultrasound in Characterization of Focal Nodular Hyperplasia Smaller Than 3 cm.

OBJECTIVES: This study aimed to compare the diagnostic efficacy of contrast-enhanced ultrasound (CEUS), including SonoVue (SV; sulfur hexafluoride; Bracco SpA, Milan, Italy) and Sonazoid (SZ; perflubutane; GE Healthcare, Oslo, Norway), and explore the differences between them in the characterization of CEUS features in focal nodular hyperplasia (FNH) smaller than 3 cm. METHODS: This retrospective study included 31 lesions smaller than 3 cm diagnosed as FNH by CEUS between April 2019 and November 2019. Nine patients underwent SZ CEUS examinations, and 22 patients underwent SV CEUS examinations; all of them were confirmed by pathologic examinations or 2 other kinds of CEUS methods. We compared the CEUS features between SZ and SV in different phases, including arterial, portal venous, delayed, and Kupffer (SZ) phases. RESULTS: Twenty-eight lesions were eventually diagnosed as FNH; 3 were misdiagnosed as FNH by SV CEUS. The overall diagnostic accuracy of CEUS including SZ and SV was 90.3% (28 of 31). No significant difference was found (P > .05) for the positive predictive value. Likewise, no significant difference in depicting centrifugal filling (9 of 9 versus 19 of 19), spoke wheel artery (6 of 9 versus 8 of 19), or feeding artery (2 of 9 versus 10 of 19) features was found between the contrast agents; However, SZ was significantly better at depicting the presence of a central scar than SV (5 of 9 versus 3 of 19; P = .030). Misdiagnosed cases are discussed in detail. CONCLUSIONS: Contrast-enhanced ultrasound enables an accurate diagnosis in FNH smaller than 3 cm. Sonazoid CEUS and SV CEUS were comparable in diagnosing small FNH, and both agents were highly capable of depicting the centrifugal filling dynamic process of FNH smaller than 3 cm. Sonazoid CEUS might be better than SV CEUS at depicting a central scar.

Research Advances in Clinical and Imaging Characteristics of Intraductal Papillary Mucinous Neoplasm of the Bile Duct.

Understanding on the intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) has dramatically improved in the past three decades. A new disease named intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) reported in recent years shares several similar clinical features with IPMN-P. The clinical manifestations and imaging characteristics of IPMN-B have been gradually recognized. This review summarizes some of the typical cases reported since 2000 and find that clinical manifestations of IPMN-B include epigastric discomfort,biliary colic,jaundice,intermittent fever,sometimes without any symptoms; imaging triads for IPMN-B are mucobilia,dilated bile duct,and bile duct mural nodule.

Initial Experience in the Application of Virtual Touch Tissue Quantification in the Differential Diagnosis of Focal Pancreatic Lesions.

Objective To explore the potential value of the virtual touch tissue quantification (VTQ) in the differential diagnosis of focal pancreatic lesions. Methods Totally 51 patients with focal pancreatic lesions underwent the quantitative analysis by VTQ. Based on the pathologic or clinical diagnosis,the VTQ values including lesional shear wave velocity (LSWV),parenchymal shear wave velocity (PSWV),and difference shear wave velocity (DSWV)(DSWV=LSWV-PSWV) were compared between the lesions and background parenchyma. Results The mean LSWV and PSWV were (2.39±1.25) m/s(0.60-4.39 m/s) and (1.59±0.63) m/s (0.76-3.22 m/s) in malignant group,(1.92±1.07) m/s(0.79-4.00 m/s) and (1.43±0.41) m/s(0.80-2.23 m/s) in potentially malignant group,and (2.40±1.10) m/s (0.89-3.42 m/s) and (1.48±0.44) m/s (1.03-2.11 m/s) in benign group. There were statistically significant difference between LSWV and PSWV in bengin and malignant group (P=0.029,P=0.005),while no statistical significance in potential malignant group (P=0.087). However,LSWV,PSWV,and DSWV showed no significant difference among these three groups (P=0.401,P=0.638,P=0.625,respectively). LSWV was not significantly associated with the tumor size (r=0.253,P>0.05) but had negative correlation with the depth of region of interest (r=-0.413,P<0.05). Conclusion VTQ may be valuable in the differential diagnosis of focal pancreatic lesions,although further research is still required.

Value of Acoustic Radiation Force Impulse Imaging in the Diagnosis of Early Non-alcoholic Steatohepatitis.

Objective To evaluate the value of acoustic radiation force impulse(ARFI)imaging in the diagnosis of early non-alcoholic steatohepatitis(NASH).Methods Totally 32 SD rats were randomly divided into high-fat diet group(n=24)and normal-diet group(n=8)by using the random number table. At the end of the 4th,8th,12th,and 16th week,six rats from the high-diet group and two rats from the normal-diet group were selected blindly for weighting,blood biochemical test,conventional ultrasound,and ARFI imaing. HE staining was used for pathological observation. Results None of the 32 rats developed liver fibrosis. Based on the pathological results,these rats were divided into M1 [mild-to-moderate simple fatty liver(SS)],M2(severe SS),M3(severe SS with early NASH),and C groups(normal control). Early NASH was seen only in the severe hepatic steatosis groups,and its distribution had a significant difference(P=0.006). The diagnostic accuracy of conventional ultrasound based on histological results was 34.4%(11/32). The ARFI value of M3 group was significantly lower than that of M2 group [(1.16±0.04)m/s vs.(1.22±0.05)m/s;t=2.301,P=0.04),and the low-density lipoprotein of M3 group was significantly higher than M2 group [(1.53±0.07)mmol/L vs.(1.21±0.22)mmol/L;t=3.075,P=0.01),while other clinical indicators had no statistical difference between these two groups. Conclusions The development of early NASH is associated with the severity of hepatic steatosis. ARFI value can provide important information to identify early NASH in patients with severe hepatic steatosis.

Value of Contrast-enhanced Ultrasound for Small Focal Liver Lesions.

Objective To explore the diagnostic value of contrast-enhanced ultrasound (CEUS)for small focal liver lesions (FLLs). Methods The clinical data,CEUS findings,and pathology of 69 patients with small FLLs were retrospectively analyzed. Patients were grouped according to size of FLLs and the performance of CEUS was compared. Results The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value of CEUS for the 69 FLLs were 94.2%,95.2%,93.8%,87.0%,and 97.8%,respectively. Rate of fast wash-out in portal vein phase was lower in group of diameters ≤2 cm than that in group of diameters>2 cm (P<0.05). Conclusions CEUS has a high diagnostic value for small FLLs.However,the CEUS findings of malignant lesions smaller than 2 cm are not typical in the portal phase and therefore the diagnosis should also be based on clinical features.

Development of a Clinicopathological-Radiomics Model for Predicting Progression and Recurrence in Meningioma Patients.

RATIONALE AND OBJECTIVES: Tumor progression and recurrence（P/R）after surgical resection are common in meningioma patients and can indicate poor prognosis. This study aimed to investigate the values of clinicopathological information and preoperative magnetic resonance imaging (MRI) radiomics in predicting P/R and progression-free survival (PFS) in meningioma patients. METHODS AND MATERIALS: A total of 169 patients with pathologically confirmed meningioma were included in this study, 54 of whom experienced P/R. Clinicopathological information, including age, gender, Simpson grading, World Health Organization (WHO) grading, Ki-67 index, and radiotherapy history, as well as preoperative traditional radiographic findings and radiomics features for each MRI modality (T1-weighted, T2-weighted, and enhanced T1-weighted images) were initially extracted. After feature selection, the optimal performance was estimated among the models established using different feature sets. Finally, Cox survival analysis was further used to predict PFS. RESULTS: Ki-67 index, Simpson grading, WHO grading, and radiotherapy history were found to be independent predictors for P/R in the multivariate regression analysis. This clinicopathological model had an area under the curve (AUC) of 0.865 and 0.817 in the training and testing sets, respectively. The performance of the combined radiomics model reached 0.85 and 0.84, respectively. A clinicopathological-radiomics model was then established, which significantly improved the prediction of meningioma P/R (AUC = 0.93 and 0.88, respectively). Finally, the risk ratio was estimated for each selected feature, and the C-index of 0.749 was obtained. CONCLUSION: Radiomics signatures of preoperative MRI have the ability to predict meningioma at the risk of P/R. By integrating clinicopathological information, the best performance was achieved.

Contrast-enhanced ultrasonography for early prediction of response of neoadjuvant chemotherapy in breast cancer.

Neoadjuvant chemotherapy (NAC) is widely accepted as a primary treatment for inoperable or locally advanced breast cancer before definitive surgery. However, not all advanced breast cancers are sensitive to NAC. Contrast-enhanced ultrasonography (CEUS) has been considered to assess tumor response to NAC as it can effectively reflect the condition of blood perfusion and lesion size. Therefore, this study aimed to evaluate the diagnostic performance of CEUS to predict early response in different regions of interest in breast tumors under NAC treatment. This prospective study included 82 patients with advanced breast cancer. Parameters of TIC (time-intensive curve) between baseline and after the first cycle of NAC were calculated for the rate of relative change (Δ), including Δpeak, ΔTTP (time to peak), ΔRBV (regional blood volume), ΔRBF (regional blood flow) and ΔMTT (mean transit time). The responders and non-responders were distinguished by the Miller-Payne Grading (MPG) system and parameters from different regions of tumors were compared in these two groups. For ROI 1(the greatest enhancement area in the central region of the tumor), there were significant differences in Δpeak1, ΔRBV1 and ΔRBF1 between responders and non-responders. For ROI 2 (the greatest enhancement area on edge of the tumor), there were significant differences in Δpeak2 and ΔRBF2 between the groups. The Δpeak1 and ΔRBF2 showed good prediction (AUC 0.798-0.820, p ≤ 0.02) after the first cycle of NAC. When the cut-off value was 0.115, the ΔRBF2 had the highest diagnostic accuracy and the maximum NPV. Quantitative TIC parameters could be effectively used to evaluate early response to NAC in advanced breast cancer.

Influence of High Sulfate Mine Water on Spontaneous Combustion of Coal.

Mine water cannot be discharged until it has been treated, which increases the cost of mining and causes environmental damage. This paper attempted to use sulfate mine water as a flame retardant material for the treatment of coal spontaneous combustion (CSC) in underground mines. The temperature-programed experimental device and gas chromatograph were used to simulate the low-temperature oxidation process of coal. Infrared spectroscopy was used to study the influence and inhibition mechanism of mine water and chloride inhibitor on active functional groups. It was found that although the sulfate mine water inhibited the formation of -OH, it accelerated the cleavage of the aromatic ring. The thermogravimetric experiment was used to analyze the ignition temperature and activation energy of different coal samples. It was found that mine water had an obvious effect on inhibiting CSC in the combustion stage, which could increase the oxidation temperature of coal.

Correlation study of periodontitis with cognitive impairment.

OBJECTIVES: This study aimed to determine the association of periodontitis with cognitive impairment by evaluating periodontal conditions in middle-aged and elderly people of normal cognition and cognitive impairment. METHODS: Forty patients with cognitive impairment and thirty-five healthy controls were included in this study. Mini-mental state examination (MMSE) was used to evaluate the level of cognitive function in all patients and controls. Periodontal conditions including severity of periodontitis, number of remaining teeth, percentage of bleeding on probing, probing depth (PD), and attachment level (AL) were examined. Periodontal conditions were compared between patients and controls, and the correlation between periodontal conditions and cognitive-function level was analyzed. Statistical analysis was performed with SPSS 26.0. RESULTS: The distribution of severity of periodontitis significantly differed between patients and controls (χ2=13.309 and P=0.001). The proportion of severe periodontitis in the cognitive-impairment group was significantly higher than that in the healthy controls (P<0.05). The percentage of sites with PD≥6 mm and AL≥5 mm in the cognitive-impairment group was higher than that in the controls, whereas the percentage of sites with PD=1-3 mm and AL=0-2 mm was higher in the controls (P<0.05). No significant difference in percentage of bleeding on probing was found in the two groups (P>0.05). Patients with cognitive impairment had fewer teeth than the controls (P<0.05). The level of cognitive function, assessed by MMSE, was positively correlated with the number of teeth and the percentage of sites with AL=0-2 mm, and it was negatively correlated with the percentage of sites with AL≥5 mm (P<0.05). CONCLUSIONS: A correlation existed between periodontitis and cognitive impairment. Further study is essential to explore the specific relationship and related mechanism between periodontitis and cognitive impairment.

Focused Ultrasound-Augmented Cancer Phototheranostics Using Albumin-Indocyanine Green Nanoparticles.

The purpose of this study was to develop a nanoparticle (NP) drug-loading system that enhances the efficiency of indocyanine green (ICG) entry into the tissue under focused ultrasound optimization and, in turn, enables more efficient identification and photothermal therapy (PTT) of the tumor. The new NPs were prepared by assembling intermolecular disulfide bonds to form human serum albumin (HSA) NPs and then conjugating those with ICG dye. The NP material was used to test the sensitivity of near-infrared fluorescence imaging and photoacoustic tumor imaging in vitro and in vivo. In addition, the combination of HSA-ICG NPs, focused ultrasound, and microbubbles was used to test PTT on the tumor. HSA-ICG NPs had good biocompatibility and were only a little toxic to cells and mice. In addition, they obviously enhanced tumor near-infrared fluorescence and photoacoustic bimodal imaging. Combined with HSA-ICG NPs, the depth of photoacoustic imaging was increased. Moreover, ICG that was absorbed in the HSA NPs promoted optical absorption in the near-infrared region, which greatly enhanced the PTT treatment's efficiency. This new bimodal tumor-imaging agent enhances the therapeutic effect of PTT and improves the detection of tumors in vivo, thus presenting great potential for use in clinical studies.

A Clinical Semantic and Radiomics Nomogram for Predicting Brain Invasion in WHO Grade II Meningioma Based on Tumor and Tumor-to-Brain Interface Features.

BACKGROUND: Brain invasion in meningioma has independent associations with increased risks of tumor progression, lesion recurrence, and poor prognosis. Therefore, this study aimed to construct a model for predicting brain invasion in WHO grade II meningioma by using preoperative MRI. METHODS: One hundred seventy-three patients with brain invasion and 111 patients without brain invasion were included. Three mainstream features, namely, traditional semantic features and radiomics features from tumor and tumor-to-brain interface regions, were acquired. Predictive models correspondingly constructed on each feature set or joint feature set were constructed. RESULTS: Traditional semantic findings, e.g., peritumoral edema and other four features, had comparable performance in predicting brain invasion with each radiomics feature set. By taking advantage of semantic features and radiomics features from tumoral and tumor-to-brain interface regions, an integrated nomogram that quantifies the risk factor of each selected feature was constructed and had the best performance in predicting brain invasion (area under the curve values were 0.905 in the training set and 0.895 in the test set). CONCLUSIONS: This study provided a clinically available and promising approach to predict brain invasion in WHO grade II meningiomas by using preoperative MRI.

Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography.

Two-dimensional shear wave elastography (2D-SWE) is a rapid, simple and novel noninvasive method that has been proposed for assessing hepatic fibrosis in patients with chronic liver diseases (CLDs) based on measurements of liver stiffness. 2D-SWE can be performed easily at the bedside or in an outpatient clinic and yields immediate results with good reproducibility. Furthermore, 2D-SWE was an efficient method for evaluating liver fibrosis in small to moderately sized clinical trials. However, the quality criteria for the staging of liver fibrosis are not yet well defined. Liver fibrosis is the main pathological basis of liver stiffness and a key step in the progression from CLD to cirrhosis; thus, the management of CLD largely depends on the extent and progression of liver fibrosis. 2D-SWE appears to be an excellent tool for the early detection of cirrhosis and may have prognostic value in this context. Because 2D-SWE has high patient acceptance, it could be useful for monitoring fibrosis progression and regression in individual cases. However, multicenter data are needed to support its use. This study reviews the current status and future perspectives of 2D-SWE for assessments of liver fibrosis and discusses the technical advantages and limitations that impact its effective and rational clinical use.

Application of superb microvascular imaging in focal liver lesions.

AIM: To explore the ability of superb microvascular imaging (SMI) in differential diagnosis of focal liver lesions (FLLs) and to compare SMI morphology findings to those of color Doppler ultrasound and enhanced imaging. METHODS: Twenty-four patients with 31 FLLs were included in our study, with diagnoses of hemangioma (HE) (n = 17), hepatocellular carcinoma (HCC) (n = 5), metastatic lesions (n = 5), primary hepatic lymphoma (n = 1), focal nodular hyperplasia (FNH) (n = 2), and adenoma (n = 1). Nine lesions were pathologically diagnosed, and 22 lesions were radiologically confirmed, all of which were evaluated by at least two types of enhanced imaging techniques. All patients had undergone SMI. Patients were divided into subgroups based on pathological and radiological diagnoses to analyze SMI manifestations. We also compared the SMI manifestations of the most common malignant FLLs (HCCs and metastatic lesions) with those of the most common benign FLLs (HEs). RESULTS: HEs were classified into three SMI subgroups: diffuse dot-like type (n = 6), strip rim type (n = 8), and nodular rim type (n = 3). The sizes of the three types of HEs were significantly different (P = 0.00, < 0.05). HCCs were classified into two subgroups: diffuse honeycomb type (n = 2) and non-specific type (n = 3). Four of the metastatic lesions were the strip rim type, and the other metastatic lesion was the thick rim type, which is the same as that of lymphoma. FNH was described as a spoke-wheel type, and adenoma as a diffuse honeycomb type. The SMI types of HCCs and metastatic lesions were significantly different from those of HEs (P = 0.048, < 0.05). CONCLUSION: SMI technology enables microvascular evaluation of FLLs without using any contrast agent. For HEs, lesion size may affect SMI performance. SMI is able to provide useful information for differential diagnosis of HCCs and metastatic lesions from HEs.

A Case Report of Male Occult Breast Cancer First Manifesting as Axillary Lymph Node Metastasis With Part of Metastatic Mucinous Carcinoma.

Occult breast cancer (OBC) is a type of breast cancer without any symptoms in the breast (no primary cancer lesion is found in either breast on a physical examination or imaging examination such as ultrasound and mammography). The incidence of OBC is rare in females, whereas in males, there are few cases of breast cancer, and the rate of OBC is very low. This is the first time report a case of male OBC first manifested as axillary metastasis, of which the pathological results showed moderately differentiated adenocarcinoma with part of metastatic mucinous carcinoma.A 40-year-old male patient presenting palpable masses in his left axillary on physical and imaging examination revealed unremarkable despite of multiple swollen lymph nodes in the left axillary, and the resected sample showed metastatic adenocarcinoma with part of metastatic mucinous carcinoma. Based on immunohistochemical analysis, positive of estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (Her-2), it was identified as an OBC.This is the fourth case report of male OBC in the literature; 1 case was reported in China in 2008, and it was metastatic infiltrating ductal carcinoma, and 2 cases were reported in Korea in 2012, one of which was reported as metastatic carcinoma and the other was metastatic adenocarcinoma; however, our case was a moderately differentiated adenocarcinoma with part of mucinous carcinoma. Our case of male OBC could metastasize to supraclavicular region and lung in addition to axillary lymph nodes, and the prognosis was relatively poor compared to the 3 cases reported before.The aim of this case report is to introduce the imaging, pathological features, and management of a rare male OBC.

Discovery, synthesis, and structure-activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2ß1γ1 activators.

Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype α2ß1γ1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure-activity relationship study showed that the amine derivatives at the 24-position (groups I-VI) can improve the potency (EC50: 0.7-2.3 µM) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 µM) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model.