Treatment of intracranial aneurysms with pipeline embolization device: a single-center experience.

Background: Endovascular therapy is the primary treatment modality for intracranial aneurysms (IA). The objective of this study was to assess the effectiveness and safety of a pipeline embolization device (PED) for the treatment of IA. Methods: This retrospective study was conducted at a single center. Data were collected for all patients who underwent PED treatment at the Fourth Affiliated Hospital of Xinjiang Medical University between December 2018 and January 2022. Clinical characteristics, aneurysm-related characteristics, treatment details, and clinical and imaging outcomes were collected and analyzed. Results: A total of 60 consecutive patients with 60 IAs were treated with a PED. The mean age of the participants was 61.8 years, with 53% being female. The average size of the aneurysms was 14.7 mm, with 54 located in the anterior circulation and six in the posterior circulation. The median last follow-up time was 13.0 months (range, 11-24 months). All patients underwent final digital subtraction angiography (DSA) for angiographic follow-up, and 50 aneurysms (83.3%) were completely occluded. The overall complication rate was 3.3%, and there were no reported mortalities. Among the 12 cases of ruptured aneurysms, all of which underwent adjunctive coil embolization, the complete occlusion rate was 91.7% with a complication rate of 16.6% [ischemic complication and modified Rankin scale (mRS) deteriorated]. In the 6 cases of posterior circulation aneurysms (2 in the basilar artery), 5 cases achieved complete occlusion and 1 case achieved near-complete occlusion, with no reported complications or mortality. Conclusions: The use of PEDs appears to be an effective treatment option for IA, demonstrating high occlusion rates and low complication rates. While the application of PEDs for the treatment of ruptured aneurysms did not increase the risk of secondary aneurysm rupture, caution is still warranted due to a higher complication rate. In the treatment of aneurysms of the vertebrobasilar artery using PEDs, this study achieved favorable efficacy outcomes without complications nor patient mortality. However, further studies are needed to validate these findings.

Purification and Structural Characterization of Polysaccharides from Polygonum multiflorum Thunb. and Their Immunostimulatory Activity in RAW264.7 Cells.

Polygonum multiflorum Thunb. (PM) and derived products are broadly utilized in Chinese traditional medicine. According to our previous research, PM mostly contains polysaccharides, which display a wide range of biological activities. Two water-soluble polysaccharides (PMPs-1 and PMPs-2) were obtained from PM by DEAE-Cellulose and Sephadex G-100 column chromatography. Colorimetry, HPGPC-MALLS-RID, HPLC-PDA, methylation, FT-IR, NMR, and SEM were used to characterize these polysaccharides. PMPs-1 and PMPs-2 had average molecular weights of 255.5 and 55.7 kDa, respectively. PMPs-1 consisted of Man, Glc, Gal, and Ara at 0.9:78.6:1.0:1.6 and was a glucan with → 4)-Glcp-(1 → as a backbone. Meanwhile, PMPs-2, an acidic polysaccharide, comprised Rha, GalA, Glc, Gal, and Ara at 3.2:20.3:2.7:1.0:8.3. PMPs-1 and PMPs-2 significantly improved the proliferation of RAW 264.7 cells and induced NO, TNF-α, and IL-6 release. This study reveals that these two polysaccharides can be explored as novel immunomodulators and provide a basis for further development of PM in food and pharmaceutical industries.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Progress in methods for the detection of viable Escherichia coli.

Escherichia coli (E. coli) is a prevalent enteric bacterium and a necessary organism to monitor for food safety and environmental purposes. Developing efficient and specific methods is critical for detecting and monitoring viable E. coli due to its high prevalence. Conventional culture methods are often laborious and time-consuming, and they offer limited capability in detecting potentially harmful viable but non-culturable E. coli in the tested sample, which highlights the need for improved approaches. Hence, there is a growing demand for accurate and sensitive methods to determine the presence of viable E. coli. This paper scrutinizes various methods for detecting viable E. coli, including culture-based methods, molecular methods that target DNAs and RNAs, bacteriophage-based methods, biosensors, and other emerging technologies. The review serves as a guide for researchers seeking additional methodological options and aiding in the development of rapid and precise assays. Moving forward, it is anticipated that methods for detecting E. coli will become more stable and robust, ultimately contributing significantly to the improvement of food safety and public health.

Copper-containing POM-based hybrid P2Mo22V4Cu4 nanocluster as heterogeneous catalyst for the light-driven hydroxylation of benzene to phenol.

The current traditional phenol production process has many shortcomings, and the efficient and clean photocatalytic one-step oxidation to phenol is gradually attracting attention. Heteropolyacids (PMo10V2) with high-density Lewis acid active sites and excellent photoelectron transfer ability are ideal choices for catalytic reactions. In this study, a copper-modified isolated dimeric hybrid nanocluster, [Cu(pyim)2]2[Cu(pyim)2(P2MoVI20MoV2VIV4O82)]2·(H2O) (pyim = [2-(pyridin-2-yl)imidazole]), was synthesized by a convenient hydrothermal method. The structural analysis demonstrated that the compound was composed of metal-organic complexes containing pyim ligands, Keggin-type heteropolyacids, and transition metal copper ions. Remarkably, this not only solves the difficulty that the heteropolymeric acid cannot be recovered by dissolving in the solvent but also introduces the copper atom as a second active center. The catalyst exhibited a benzene conversion of 15.6% and a selectivity of 85.2% in a mixed solution of acetonitrile and acetic acid under optimal reaction conditions. After four catalytic cycles, the PXRD pattern proved that the catalyst was still stable. This study provides a good idea for photocatalytic reactions and other environmental applications.

Anti-aging activities of neutral and acidic polysaccharides from Polygonum multiflorum Thunb in Caenorhabditis elegans.

Polygonum multiflorum Thunb (PM) is used to slow the aging process. Although polysaccharides are a major constituent of PM, their anti-aging properties have not been thoroughly investigated. Therefore, this study aimed to examine the anti-aging effects of polysaccharides extracted from PM using the Caenorhabditis elegans (C. elegans) model. Two types of water-soluble heteropolysaccharides, namely a neutral polysaccharide (RPMP-N) and an acidic polysaccharide (RPMP-A), were obtained from PM. Their structures were elucidated by various methods. The effects of these polysaccharides on the lifespan, levels of antioxidants, and activities of antioxidant-related enzymes in C. elegans were also evaluated. The results showed that RPMP-A had higher GalA content compared with RPMP-N. The average molecular weights of RPMP-N and RPMP-A were 245.30 and 28.45 kDa, respectively. RPMP-N is a α-1,4-linked dextran as the main chain, and contains a small amount of branched dextran with O-6 as the branched linkage site；RPMP-A may be a complex of α-1,4-linked dextran, HG and RG-I. Treatment with RPMP-N and RPMP-A increased the mean lifespan of C. elegans, and significantly regulated oxidative stress. RPMP-A exhibited stronger anti-aging effects compared with RPMP-N. These findings suggest that RPMP-A may be a potent antioxidant and anti-aging component that can be used for developing functional food products and effective dietary supplements.

Endovascular re-canalization for symptomatic non-acute intracranial large artery occlusion: a single-center retrospective study.

Background: Managing patients with symptomatic non-acute intracranial large artery occlusion (SNA-ILAO) poses a significant challenge due to the high morbidity and risk of recurrent critical ischemic events, even with standard medical therapy. This unique subgroup of patients requires specialized attention. The aim of this study is to evaluate the feasibility and safety of endovascular interventional recanalization for SNA-ILAO. Methods: We retrospectively collected data of patients with SNA-ILAO who underwent endovascular interventional therapy at the Fourth Affiliated Hospital of Xinjiang Medical University from 2018 to 2021. The collected data included clinical demography, imaging data, treatment details, and prognosis. Follow-up imaging assessments were conducted for the patients, and descriptive statistics were performed. Results: A total of 24 patients were enrolled, with a majority being male (58.3%) and a mean age of 62.0±9.3 years. The pre-treatment median modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) scores at baseline were 3 and 1, respectively. The most common occlusion location was the middle cerebral artery (MCA), including M1 (70.8%), M2 (20.8%), and M3 (4.7%). Successful recanalization was achieved in all 24 patients, with 21 cases (87.5%) achieving thrombolysis in cerebral infarction (TICI) 3 reperfusion and the remaining 3 cases (12.5%) achieving TICI 2b reperfusion. Asymptomatic intracranial hemorrhage (ICH) occurred in 2 patients (8.3%). During the first 30-day clinical follow-up, none of these patients experienced any recurrent cerebral ischemic events. During the 29.5-month follow-up period for vessel imaging, only 12.5% (3/24) of patients who had follow-up imaging experienced re-stenosis. Conclusions: Endovascular recanalization is a potentially safe and effective procedure for patients with SNA-ILAO. However, it is important to note that there is still a non-negligible rate of complications associated with this treatment. Therefore, exercising caution and implementing strict controls when administering this procedure is crucial.

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).

An epi-allele of SMS causes Sanming dominant genic male sterility in rice.

Male sterility is an important trait in rice for hybrid rice (Oryza sativa) breeding. However, the factors involved in dominant male sterility are largely unknown. Here, we identified a gene from Sanming dominant genic male sterile rice, named Sanming dominant male sterility (SMS), and reported that an epi-allele of this locus contributes to male sterility. Segregation analysis attributed dominant male sterility to a single locus, SMS, which we characterized using a male-sterile near isogenic line (NIL) of rice cultivar 93-11. The SMS locus was heterozygous in the male-sterile 93-11 NIL, containing an epi-allele identical to that in 93-11, and an epi-allele identical to that in rice cultivar Nipponbare, which we refer to as SMS9 and SMSN, respectively. SMS9 is silent and hyper-methylated, whereas SMSN is expressed and hypo-methylated in the 93-11 NIL. Overexpressing SMSN led to male sterility. Mutations in SMS rescued the male sterility of the 93-11 NIL. Interestingly, we observed the duplication of SMSN in Nipponbare, but did not observe the duplication of SMS9 in 93-11. Together, these findings suggest that the reduced methylation and enhanced expression of the SMSN epi-allele in the 93-11 NIL is responsible for its role in conferring dominant male sterility.

The role of gut archaea in the pig gut microbiome: a mini-review.

The gastrointestinal microbiota of swine harbors an essential but often overlooked component: the gut archaea. These enigmatic microorganisms play pivotal roles in swine growth, health, and yield quality. Recent insights indicate that the diversity of gut archaea is influenced by various factors including breed, age, and diet. Such factors orchestrate the metabolic interactions within the porcine gastrointestinal environment. Through symbiotic relationships with bacteria, these archaea modulate the host's energy metabolism and digestive processes. Contemporary research elucidates a strong association between the abundance of these archaea and economically significant traits in swine. This review elucidates the multifaceted roles of gut archaea in swine and underscores the imperative for strategic interventions to modulate their population and functionality. By exploring the probiotic potential of gut archaea, we envisage novel avenues to enhance swine growth, health, and product excellence. By spotlighting this crucial, yet under-investigated, facet of the swine gut microbiome, we aim to galvanize further scientific exploration into harnessing their myriad benefits.

Retrospective comparison of false-positive result frequencies of 3 syphilis serology screening tests in pregnant and nonpregnant patients at an academic medical center in Appalachia.

OBJECTIVE: This study retrospectively compared false-positive result frequencies of 3 syphilis serology screening tests and assessed whether false positivity was associated with pregnancy and age. METHODS: Results for 3 screening tests were retrieved from the laboratory database, including rapid plasma reagin (RPR) assay between October 2016 and September 2019, BioPlex 2200 Syphilis Total immunoassay between May 2020 and January 2022, and Alinity i Syphilis TP assay between February 2022 and April 2023. The false-positive result frequencies were calculated based on testing algorithm criteria. RESULTS: False-positive result frequency for BioPlex was 0.61% (90/14,707), significantly higher than 0.29% (50/17,447) for RPR and 0.38% (55/14,631) for Alinity (both P < .01). Patients with false-positive results were significantly older than patients with nonreactive results for RPR (median age: 36 vs 28, P < .001), but not for BioPlex or Alinity. For all 3 tests, the positive predictive values in pregnant women were lower than those in nonpregnant women or men. However, pregnant women did not exhibit a higher false-positive result frequency. CONCLUSION: Although false-positive result frequencies were low overall for all 3 syphilis serology tests, there is a significant difference between different tests. Pregnancy was not associated with more false-positive results for all 3 tests.

The relationship between coronary artery calcification and bone metabolic markers in maintenance hemodialysis patients.

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.

Impacts of cigarette smoking on blood circulation: do we need a new approach to blood donor selection?

Smoking is a major public health problem and is considered the leading cause of preventable death worldwide. Gas-phase smoke carries bioactive substances and toxic compounds, affecting human health and reducing life spans. The negative effects of smoking on red blood cell (RBC) quality include destroying RBCs and increasing carboxy hemoglobin (COHb). Smoking increases the concentrations of heavy metals such as cadmium (Cd) and lead (Pb) in the blood. Moreover, tobacco smoking has been found to be associated with heightened platelet (PLT)-dependent thrombin level which will induce a prothrombotic state. Smoking may affect the blood circulation of donors, and subsequently the blood components, and ultimately the recipients of transfusion. Nevertheless, there are no restrictions on smoking for volunteer blood donor screenings currently. We reviewed the articles about the influence of smoking on smokers' blood circulation as well as the impact of donated blood products on transfusion when these smokers act as blood donors. We aim to attract blood collection centers' attention to strengthen the management of blood donors who smoke, avoiding their use in massive transfusion protocol and susceptible recipients, especially pediatric ones.

Advances in detection methods for viable Salmonella spp.: current applications and challenges.

Salmonella is a common intestinal pathogen that can cause food poisoning and intestinal disease. The high prevalence of Salmonella necessitates efficient and sensitive methods for its identification, detection, and monitoring, especially of viable Salmonella. Conventional culture methods need to be more laborious and time-consuming. And they are relatively limited in their ability to detect Salmonella in the viable but non-culturable status if present in the sample to be tested. As a result, there is an increasing need for rapid and accurate techniques to detect viable Salmonella spp. This paper reviewed the status and progress of various methods reported in recent years that can be used to detect viable Salmonella, such as culture-based methods, molecular methods targeting RNAs and DNAs, phage-based methods, biosensors, and some techniques that have the potential for future application. This review can provide researchers with a reference for additional method options and help facilitate the development of rapid and accurate assays. In the future, viable Salmonella detection approaches will become more stable, sensitive, and fast and are expected to play a more significant role in food safety and public health.

On-line identification of the chemical constituents of Polygoni Multiflori Radix by UHPLC-Q-ToF MS/MS.

Introduction: Polygoni Multiflori Radix (PMR) is a type of Chinese herbal medicine with rich chemical composition and pharmacological activity used widely in medicine and food. However, in recent years, there have been increasing numbers of negative reports about its hepatotoxicity. Identification of its chemical constituents for quality control and safe use is very important. Methods: Three solvents of different polarities (water, 70% ethanol, and 95% ethanol solution) were used to extract the compounds from PMR. Extracts were analyzed and characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-ToF MS/MS) in the negative-ion mode. Results: 152 compounds were detected and identified: 50 anthraquinones, 33 stilbene derivatives, 21 flavonoids, seven naphthalene compounds, and 41 other compounds. Eight other compounds were reported for the first time in the PMR-related literature, and eight other compounds were potentially new compounds. Discussion: This study lays a solid foundation for the screening of toxicity and quality-control indicators of PMR.

Organoid models derived from patients with malignant phyllodes tumor of the breast.

PURPOSE: Phyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It's urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients. METHODS: Two surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively. RESULTS: We successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines. CONCLUSION: Organoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

Dianthrone derivatives from Polygonum multiflorum Thunb: Anti-diabetic activity, structure-activity relationships (SARs), and mode of action.

PTP1B plays an important role as a key negative regulator of tyrosine phosphorylation associated with insulin receptor signaling in the therapy for diabetes and obesity. In this study, the anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb., as well as the structure-activity relationships, mechanism, and molecular docking were explored. Among these analogs, trans-emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. By using photoaffinity labeling and mass spectrometry-based proteomics, we discovered that trans-emodin dianthrone (compound 1) may bind to PTP1B allosteric pocket at helix α6/α7, which provides fresh insight into the identification of novel anti-diabetic agents.

Innovative accumulative risk assessment strategy of co-exposure of As and Pb in medical earthworms based on in vivo-in vitro correlation.

Recent studies on risks assessment of heavy metal(loid) are usually based on their total concentrations. Nevertheless, such an analysis does not assess their real amounts absorbed by human body. To scientifically assess the health risks, in this study medical earthworms were analyzed for relative bioavailability (RBA) of arsenic (As) and lead (Pb) using a multiple gavage mouse model with liver, kidneys, brain, and leg bones as biomarkers for the first time. Metal(loid) bioaccessibility was determined using in vitro physiologically based extraction (PBET) assay. We are the first to develop a novel accumulative health risk assessment strategy by combinational analyzing bioavailability of heavy metal(loid) levels to calculate target organ toxicity dose (TTD) modification of the HI and total cancer risk (TCR), which has capacity to evaluate the health risks of co-exposure of Pb and As in medical earthworms. As a result, As-RBA ranged from 7.2% to 45.1%, and Pb-RBA ranged from 16.1% to 49.8%. Additionally, As and Pb bioaccessibility varied from 6.7% to 48.3% and 7.8% to 52.5%, respectively. Moreover, strong in vivo-in vitro correlations (IVIVCs) were observed between metal-RBA and bioaccessibility, indicating the robustness of the in vitro PBET assay to predict metal-RBA in medical earthworms. The refined accumulative assessment strategy revealed that when adjusted by heavy metal(loid) bioavailability, the TTD modification of HI method typically exhibited an acceptable health risk caused by the co-exposure of Pb and As for cardiovascular, hematological, neurological, and renal system. The TCR levels associated with exposure to Pb and As due to the ingestion of medical earthworms were also acceptable after adjustment by bioavailability. Collectively, our innovation on accumulative risk assessment based on in vivo-in vitro correlation provides a novel approach engaging in assessing the risks due to co-exposure of As and Pb in medical earthworms.