RfxCas13d-mediated inhibition of Circ1647 alleviates renal fibrosis via PI3K/AKT signaling pathway.

BACKGROUND: Circular RNAs (CircRNAs) have been shown to be involved in the development of chronic kidney disease (CKD). This study aimed to investigate the role of Circ1647 in renal fibrosis, which is a hallmark of CKD. METHODS: In this study, we established a unilateral ureteral obstruction (UUO) model and delivered Circ1647 RfxCas13d knockdown plasmid into renal parenchymal cells via retrograde injection through the ureter followed by electroporation. After that, the pathological changes were determined by Hematoxylin and Eosin. Meanwhile, Immunohistochemistry, qRT-PCR and Western blot were conducted to assess the degree of fibrosis. In addition, overexpressing of Circ1647 in renal tubular epithelial cells (TCMK1) was performed to investigate the underlying mechanisms of Circ1647. RESULTS: Our results displayed that electroporation-mediated knockdown of Circ1647 by RfxCas13d knockdown plasmid significantly inhibited renal fibrosis in UUO mice as evidenced by reduced expression of fibronectin and α-SMA (alpha-smooth muscle actin). Conversely, overexpression of Circ1647 in TCMK1 cells promoted the fibrosis. In terms of mechanism, Circ1647 may mediate the PI3K/AKT Signaling Pathway as demonstrated by the balance of the phosphorylation of PI3K and AKT in vivo and the aggravated phosphorylation of PI3K and AKT in vitro. These observations were corroborated by the effects of the PI3K inhibitor LY294002, which mitigated fibrosis post Circ1647 overexpression. CONCLUSION: Our study suggests that Circ1647 plays a significant role in renal fibrosis by mediating the PI3K/AKT signaling pathway. RfxCas13d-mediated inhibition of Circ1647 may serve as a therapeutic target for renal fibrosis in CKD.

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

Media impact research: a discrete SIR epidemic model with threshold switching and nonlinear infection forces.

The media's coverage has the potential to impact human behavior and aid in the control of emergent infectious diseases. We aim to quantify and evaluate the extent to which media coverage can influence infectious disease control through a mathematical model, thus proposing a switching epidemic model that considers the effect of media coverage. The threshold strategy incorporates media influence only when the number of infected cases surpasses a specific threshold; otherwise, it is disregarded. When conducting qualitative analysis of two subsystems, focusing on the existence and stability of equilibria. Using numerical methods, the codimension-2 bifurcation analysis is adopted here to investigate the various types of equilibria within the switching system that play a vital role in pest control. On the other hand, codimension-1 bifurcation analysis reveals the existence of periodic, chaotic solutions, period-doubling bifurcations, multiple attractors and other complexities within the proposed model, which could pose challenges in disease control. Additionally, the impact of key parameters on epidemic outbreaks is analyzed, such as the initial values of susceptible and infective individuals, and discuss the potential benefits of mass media coverage in preventing emerging infectious diseases. The modeling and analytical techniques developed for threshold control strategies can be applied to other disease control efforts.

An eco-epidemic model for assessing the application of integrated pest management strategies.

Mathematical models have become indispensable tools for analyzing pest control strategies. However, in the realm of pest control studies, the consideration of a plant population being affected by a model that incorporates pests, natural enemies and disease in the pest population has been relatively limited. Therefore, this paper aims to formulate and investigate a hybrid impulsive eco-epidemic model that incorporates disease in the pest population. Initially, we examine the existence and stability of the pest-eradication periodic solution. Subsequently, to explore the impact of chemical and biological control methods, we propose an updated eco-epidemic model that incorporates varying frequencies of pesticide sprays and the release of both infected pests and natural enemies for pest control. We establish threshold values for the susceptible pest eradication periodic solution under different scenarios, illustrating the global attractiveness of this solution. Finally, we discuss the obtained results and suggest potential avenues for future research in this field.

Unlocking the predictive potential of long non-coding RNAs: a machine learning approach for precise cancer patient prognosis.

The intricate web of cancer biology is governed by the active participation of long non-coding RNAs (lncRNAs), playing crucial roles in cancer cells' proliferation, migration, and drug resistance. Pioneering research driven by machine learning algorithms has unveiled the profound ability of specific combinations of lncRNAs to predict the prognosis of cancer patients. These findings highlight the transformative potential of lncRNAs as powerful therapeutic targets and prognostic markers. In this comprehensive review, we meticulously examined the landscape of lncRNAs in predicting the prognosis of the top five cancers and other malignancies, aiming to provide a compelling reference for future research endeavours. Leveraging the power of machine learning techniques, we explored the predictive capabilities of diverse lncRNA combinations, revealing their unprecedented potential to accurately determine patient outcomes.

lncRNAs play crucial roles in cancer biology, regulating proliferation, migration, and drug resistance.Emerging evidence suggests that machine learning can predict cancer prognosis using specific lncRNA combinations.Comprehensive information on the predictive abilities of lncRNA combinations in oncology concerning machine learning is lacking.This review offers up-to-date vital references on diverse lncRNA combinations pertinent to future research and clinical trials.

Association of Interleukin-6 Genetic Polymorphisms (rs1800795, -174C > G and rs1800796, -572G > C) With Risk of Essential Hypertension in the Chinese Population.

Background Interleukin-6 (IL-6) plays a critical role in essential hypertension (EH) and cardiovascular disease. Evidence suggests two hotspot single nucleotide polymorphisms (SNPs) of the IL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) might be associated with the susceptibility of EH. However, no consensus has yet been established. Thus, we aimed to investigate the potential association between IL-6 gene polymorphisms and the risk of EH based on a case-control study in a Chinese population. Materials and methods A total of 479 subjects (272 healthy controls and 207 EH patients) were randomly enrolled in our study. After extracting the genomic DNA, two SNPs of the IL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) were genotyped to analyze the potential association between these genetic variants and EH risk. Multiple genetic models were performed to investigate the strength of association by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The potential effect of SNPs on gene expression was evaluated using expression quantitative trait loci (eQTL) analysis. Results The genotyping findings of IL-6 rs1800795, -174C > G polymorphism showed three study participants with CG genotype and 204 with GG genotype in the EH patients. The IL-6 -174C > G polymorphism was significantly associated with EH risk (P = 0.046) and conferred a reduced risk of EH development (OR = 0.99, 95%CI = 0.97-1.00). Conversely, no substantial association between IL-6 rs1800796, -572G > C polymorphism and the risk of EH was found in all genetic models (P > 0.05). Moreover, the eQTL analysis indicated that the -174C > G polymorphism was significantly associated with gene expression of IL-6 (P = 0.006), and the G allele corresponded to a reduced IL-6 gene expression (Beta = -0.397). Compared with -174C > G, the -572G > C polymorphism was not found to be significantly associated with IL-6 gene expression (Beta = -0.120, P = 0.560). Conclusions Our findings provide evidence that the rs1800795, -174C > G polymorphism can affect the expression levels of IL-6, and the risk of EH occurrence. However, the rs1800796, -572G > C polymorphism does not regulate the IL-6 gene expression levels and the susceptibility of EH.

LIMK1 m6A-RNA methylation recognized by YTHDC2 induces 5-FU chemoresistance in colorectal cancer via endoplasmic reticulum stress and stress granule formation.

LIM kinase 1 (LIMK1) is a member of the LIMK family that has been considered to be involved in chemoresistance in various tumors, and N6-methyladenosine (m6A) is the most abundant nucleotide modification on mRNA. However, whether elevated expression of LIMK1 leads to chemoresistance due to m6A modification remains to be further studied. The findings of our study indicate that high LIMK1 expression in colorectal cancer (CRC) cells promotes cell proliferation and increases resistance to 5-fluorouracil (5-FU). Moreover, downregulation of YTH domain-containing 2 (YTHDC2), an m6A "reader", in CRC cells resulted in decreased recognition and binding to the m6A site "GGACA" in LIMK1 mRNA, thereby increasing LIMK1 mRNA stability and expression. Furthermore, the overexpression of LIMK1 facilitated eIF2α phosphorylation, which induced endoplasmic reticulum (ER) stress and promoted stress granule (SG) formation, ultimately leading to 5-FU resistance. This study evaluated the specificity of the YTHDC2/LIMK1/eIF2α signalling axis and the efficacy of related drugs in modulating 5-FU sensitivity in CRC.

B(C6F5)3-catalyzed regio- and stereoselective thiosulfonylation of terminal alkynes with thiosulfonates.

Herein, a metal-free main-group catalysis system for thiosulfonylation of terminal alkynes with thiosulfonates has been established by using commercially available B(C6F5)3 as a catalyst. The protocol provides a highly regio- and stereoselective route for the synthesis of diverse (E)-(ß)-arylthiolvinyl sulfones under mild conditions with 100% atom-economy and exceptional functional group compatibility.

VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing ß­cell dedifferentiation.

Vanin­1 (VNN1) may be a potential biomarker for the early screening of pancreatic cancer (PC)­associated diabetes (PCAD). A previous study by the authors reported that cysteamine secreted by VNN1­overexpressing PC cells induced the dysfunction of paraneoplastic insulinoma cell lines by increasing oxidative stress. In the present study, it was observed that both cysteamine and exosomes (Exos) secreted by VNN1­overexpressing PC cells aggravated the dysfunction of mouse primary islets. PC­derived VNN1 could be transported into islets through PC cell­derived Exos (PC­Exos). However, ß­cell dedifferentiation, and not cysteamine­mediated oxidative stress, was responsible for the islet dysfunction induced by VNN1­containing Exos. VNN1 inhibited the phosphorylation of AMPK and GAPDH, and prevented Sirt1 activation and FoxO1 deacetylation in islets, which may be responsible for the induction of ß­cell dedifferentiation induced by VNN1­overexpressing PC­Exos. Furthermore, it was demonstrated that VNN1­overexpressing PC cells further impaired the functions of paraneoplastic islets in vivo using diabetic mice with islets transplanted under the kidney capsule. On the whole, the present study demonstrates that PC cells overexpressing VNN1 exacerbate the dysfunction of paraneoplastic islets by inducing oxidative stress and ß­cell dedifferentiation.

Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer.

Background: Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. Methods: A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. Results: CKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8+ T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8+ T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro. Conclusions: The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.

Measurement of Slips at Contact Interfaces Using a Self-Powered Sensor Based on Triboelectric Nanogenerators.

The accumulation of tangential small slips at contact interfaces may occur in mechanical assemblies when subjected to cyclic loadings, and cause failure of parts. However, the slip is difficult to measure directly. In this paper, a self-powered displacement sensor based on triboelectric nanogenerator (TENG) is fabricated, which is used to measure the microslip of the specimen in the designed test bench. When the specimen slips under the cyclic tangential load with a frequency of 10 Hz, the resulted average slip displacement of the specimen under a single load cycle is 9.01 µm, which is measured by the Keithley DAQ 6510 multimeter (Tektronix, Shanghai, China). This value is close to that measured by the Keithley 6514 electrometer. In addition, adding a BaTiO3 thin film with a thickness of 100 nm between the Kapton triboelectric layer and the Cu electrode, the output voltage of the sensor is increased by 51.5%. Thus, the sensitivity of the self-powered sensor is improved effectively.

[Anti-tumor and analgesic activity evaluation and mechanism of Compound Kushen Injection].

This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.

Effects of biochar amendment on bioconversion of soybean dregs by black soldier fly.

Biochar is known to accelerate composting process and improve the quality of end-products. However, its effects on bioconversion of organic waste by black soldier fly larvae (BSFL) remains largely unexamined. To investigate the effects of corn straw biochar (CS-BC) on bioconversion of soybean dregs (SD) by BSFL, SD was amended with four different dosages of CS-BC [0%, 2%, 5%, and 8% (w/w)] and digested by BSFL for ten days. The results indicated that the peak values of single larva wet weight in the treatments amended with CS-BC were advanced by 2-3 days and the reduction rate of SD increased from 72.09% to 85.37% with the increasing dosage of CS-BC. Meanwhile, SD mixed with 2%, 5% and 8% of CS-BC decreased ammonia (NH3) emission by 2.7%, 3.6% and 18.0%, respectively. The nitrous oxide (N2O) emissions reduced (-23.6%, -29.1% and -49.2%) with 2%, 5% and 8% CS-BC additions, respectively. In addition, the residual nitrogen of SD­nitrogen proportionally increased with CS-BC application (28.3%, 28.6%, 30.1% and 35.0% for application at the dosage of 0%, 2%, 5% and 8%, respectively). Based on the comprehensive evaluation of bioconversion performance, alleviation of pollutant gas emission, and nitrogen conservation, we recommend the introduction of 8% (w/w) CS-BC during bioconversion of SD by BSFL. This study confirmed the feasibility of CS-BC as an amendment for the BSFL-based bioconversion system.

Pink noise removal and spectral distortion correction based fiber Bragg grating demodulation algorithm.

Pink noise and spectral distortions affect the demodulation accuracies of fiber Bragg gratings (FBGs). A noise reduction algorithm with Savitzky-Golay filtering on each intrinsic mode function component decomposed by CEEMDAN, followed by signal reconstruction from the filtered components, is presented herein. Simulations show that the algorithm retains FBG signal details while reducing noise, avoids measurement errors from excessive smoothing, and suppresses white and pink noises adequately. A resolution-enhanced peak detection algorithm with distortion spectrum correction is also proposed with high accuracy and simple calculation. The experimental results show that the goodness of fit of the FBG temperature-wavelength curve R2 improves from 0.9826 to 0.9999.

[Arthroscopic debridement combined with platelet-rich plasma injection for the treatment of Kellgren-Lawrence gradeâ -â ¢ knee osteoarthritis].

OBJECTIVE: To explore clinical effect of arthroscopic debridement combined with platelet-rich plasma (PRP) injection for Kellgren-Lawrence(K-L) gradeⅠ-Ⅲ knee osteoarthritis (KOA) . METHODS: Totally 117 patients with KOA who underwent arthroscopic debridement combined with injection from November 2015 to January 2019 were retrospectively analyzed. According to different injection drugs, the patients were divided into sodium hyaluronate group(group A) and PRP group(group B). In group A, there were 60 patients, including 27 males and 33 females, aged from 49 to 67 years old with an average age of (54.1±4.8) years old;12 patients with gradeⅠ, 23 patients with gradeⅡand 25 patients with grade Ⅲ according to K-L clssification, 2 ml(20 g) sodium hyaluronate was injected into knee joint after intraoperative, 1, 2, 3 weeks after operation for 4 times. In group B, there were 57 patients, including 25 males and 32 females, aged from 47 to 70 years old with an average of (55.8±5.0) years old, 10 patients with gradeⅠ, 20 patients with gradeⅡand 27 patients with grade Ⅲ according to K-L classification, injected 5 ml PRP at the same time. Postoperative complications was recorded between two groups. Postoperative visual analogue scale(VAS) and Lysholm score at 3, 6, 12 months were used to evaluate improvement of knee pain and joint function. RESULTS: All patients were followed up for 12 to 19 months with an average of (14.1±1.6) months. There was no significant difference in postopertaive complications between group A and group B (P>0.05). Postoperative VAS score in group A at 3, 6, 12 months were 3.0±0.8, 2.0±0.8, 2.6±0.9 respectively, and 2.9±0.8, 1.9±0.7, 2.2±0.8 in group B respectively; and no differnece at 3 and 6 months after operation between two groups (P<0.05), while VAS score in group B was higher than group A at 12 months after operation(P<0.05). Postoperative Lysholm score in group A at 1, 6, 12 months (86.6±1.8, 93.1±2.0, 86.7±1.7) were lower than group B(88.9±1.9, 95.0±2.0, 89.0±1.9)(P<0.05). CONCLUSION: Arthroscopic debridement combined with sodium hyaluronate or PRP injection for K-L gradeⅠ-Ⅲ KOA could effectively relieve pain and improve joint function with higher safety in short term, but the medium-long-term effect of PRP injection is stable.

Compound Kushen Injection Induces Immediate Hypersensitivity Reaction Through Promoting the Production of Platelet-Activating Factor via de Novo Pathway.

Compound Kushen Injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Yunnanensis). Clinically, it is used as the adjuvant treatment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. The obtained results showed that CKI did not elevate serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) after consecutive immunization for 5 weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alkaloids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various platelet-activating factor (PAF) receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway. In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

Chimera and cluster collective states in a dispersal ecological network under state-dependent feedback control and complex habitat structure.

Pest control based on an economic threshold (ET) can effectively prevent excessive pest control measures such as pesticide abuse and overharvesting. The instinctive dispersal of pest populations in biological network patches for better survival poses challenges for pest management. As long as the pest density is controlled below the economic threshold and no pest outbreak occurs, the aim of pest management can be achieved and it is not necessary to completely remove the pests. This study focuses on the issues of chimera states and cluster solutions in regular bidirectional biological networks with state-dependent impulsive pest management. We consider the influence of two different control modes on the system states, namely global control and local control. Local control is found to be more likely to induce the chimera state. In addition, in the local coupling mode, a higher coupling strength is more likely to generate a coherent state, whereas a lower coupling strength is more likely to generate chimera and incoherent states. Furthermore, the cluster size is inversely related to the coupling strength under local coupling and global control.

Fiber Bragg Grating Dynamic Calibration Based on Online Sequential Extreme Learning Machine.

The fiber Bragg grating (FBG) sensor calibration process is critical for optimizing performance. Real-time dynamic calibration is essential to improve the measured accuracy of the sensor. In this paper, we present a dynamic calibration method for FBG sensor temperature measurement, utilizing the online sequential extreme learning machine (OS-ELM). During the measurement process, the calibration model is continuously updated instead of retrained, which can reduce tedious calculations and improve the predictive speed. Polynomial fitting, a back propagation (BP) network, and a radial basis function (RBF) network were compared, and the results showed the dynamic method not only had a better generalization performance but also had a faster learning process. The dynamic calibration enabled the real-time measured data of the FBG sensor to input calibration models as online learning samples continuously, and could solve the insufficient coverage problem of static calibration training samples, so as to improve the long-term stability, accuracy of prediction, and generalization ability of the FBG sensor.

IPM strategies to a discrete switching predator-prey model induced by a mate-finding Allee effect.

This paper proposes a discrete switching predator-prey model with a mate-finding Allee effect, where also switches are guided by Allee effect. One of the strategies analysed is to use a chemical in order to prevent the pest outbreak when the pest population is free of Allee effect. In this paper, we first study analytically the dynamic behaviors of the two subsystems and the equilibria and their stability of the switched system. Then we provide numerical bifurcation analyses for the switched discrete system. These show that the switched discrete system may have very complex dynamics by 2-parameter bifurcation diagrams which divide the space into regions and study equilibria, and 1-dimensional bifurcation diagrams which reveal that the system has periodic, chaotic solutions, period doubling bifurcations and so on. Furthermore, we try to refer the key parameters and initial densities of both populations associated with pest outbreaks and study their biological implications.

[Safety evaluation of heavy metals contaminated Astragalus membranaceus using health risk assessment model].

To evaluate the safety of heavy metals contaminated Astragalus membranaceus,an appropriate protocol was established to study the heavy metals pollution level by health risk assessment. This study provided a detailed procedure to assess the medicinal herbs in quality control and safety evaluation,and expected to create awareness among the public on the safety of consuming of A. membranaceus or any other kinds of medicinal herbs. The heavy metals content of Cu,As,Cd,Pb and Hg in a total of 45 batches of A. membranaceus were carefully analyzed with a developed inductively coupled plasma mass spectrometry( ICP-MS). Besides,the heavy metal contamination level was further evaluated through 4 main assessment parameters,including maximum residue limit( MRL) set by International Standard Organization,estimated daily intake( EDI) set by IUPAC,target hazard quotients( THQ) and Total THQ set by USEPA and total THQs in raw herbs of A. membranaceus. In addition,the recommended MRLs of 5 main heavy metals aimed to A. membranaceus were calculated based on the regulated consumption quantity. The result showed that,under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 8. 89% for A. membranaceus,which including 4 batches of A. membranaceus exceeded the MRL of As. Here,the standard THQ value of A. membranaceus was firstly proposed as 0. 02 and 0. 011 25 for adults and children,respectively,which were calculated with the recommended consumption quantity of 30 g and 9 g for adults and children. Furthermore,the values of THQ for As and total THQs in adults and children were exceeded the standard THQ in A. membranaceus,and the recommended MRLs of Pb,Cd,Hg and Cu in above medicinal materials that calculated based on health risk assessment model were higher than the regulated MRLs that set by ISO and Chinese Pharmacopeia. The research showed that the contents of heavy metals in A. membranaceus were not in the safe range and the certain non-carcinogenic risks to human body cannot be neglected. Based on above investigation result,it is easily known that the common evaluation method for raw herbs based on the comparison of MRL of heavy metals was not precise enough,and the international model of health risk assessment should be built for each medicinal herb. Above all,this study provided a more realistic research approach for safety evaluation of any other kinds of heavy metals contaminated medicinal herbs,including the establishment of heavy metals standard limit in a specified medicinal herb under recommended consumption quantity,and it is expected to create awareness among the public on the safety of consuming any other medicinal herbs.