The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis - a single center retrospective case-control study.

OBJECTIVE: This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. METHODS: From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. RESULTS: (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636-0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072-10.737; adjusted OR = 15.580, 95%CI: 2.114-114.798]. CONCLUSION: Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

Sirolimus combined with glucocorticoids in the treatment of Kasabach-Merritt phenomenon in a neonate: A case report.

RATIONALE: Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS: A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS: Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS: The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES: The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS: Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.

PA-NeRF, a neural radiance field model for 3D photoacoustic tomography reconstruction from limited Bscan data.

We introduce a novel deep-learning-based photoacoustic tomography method called Photoacoustic Tomography Neural Radiance Field (PA-NeRF) for reconstructing 3D volumetric PAT images from limited 2D Bscan data. In conventional 3D volumetric imaging, a 3D reconstruction requires transducer element data obtained from all directions. Our model employs a NeRF-based PAT 3D reconstruction method, which learns the relationship between transducer element positions and the corresponding 3D imaging. Compared with convolution-based deep-learning models, such as Unet and TransUnet, PA-NeRF does not learn the interpolation process but rather gains insight from 3D photoacoustic imaging principles. Additionally, we introduce a forward loss that improves the reconstruction quality. Both simulation and phantom studies validate the performance of PA-NeRF. Further, we apply the PA-NeRF model to clinical examples to demonstrate its feasibility. To the best of our knowledge, PA-NeRF is the first method in photoacoustic tomography to successfully reconstruct a 3D volume from sparse Bscan data.

Erbium: YAG laser treatment efficacy and association with histologic features for giant congenital melanocytic nevi management.

BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.

Bee colonies map the short- and medium-chain chlorinated paraffin contamination from the apiary environment.

Chlorinated paraffins (CPs) are industrial chemicals that have potential adverse effects in the environment and on human health. This study investigated CPs in apiary environment, honeybees, and bee products from two rural areas of Beijing, China. The median concentrations of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) were 22 and 1.6 ng/m3 in the ambient air, 1350 and 708 ng/g dry mass (dw) in bees, 1050 and 427 ng/g dw in flowers, 37 and 54 ng/g in honey, 78 and 53 ng/g dw in bee pollen, 36 and 30 ng/g dw in soil, and 293 and 319 ng/g dw in bee wax. C10Cl6-7 and C14Cl7-8 dominated SCCPs and MCCPs in these samples, respectively. The concentrations and distributions of CPs in samples from apiaries located in the two regions varied. Long-range transportation of air masses was identified as an important source of CPs in apiaries. A close relationship between CPs in bees and the apiary environment indicated that bees could act as bioindicators for CP contamination in the environment. A human health risk assessment found that there were low risks for adults and children exposed to CPs through consumption of honey and pollen from the studied regions.

Investigation and analysis of the status of myopia and related behavior in children and adolescents in Northeast Sichuan.

PURPOSE: In this study, we examined the current status of myopia among primary and secondary school children in northeastern Sichuan to analyze the factors connected to myopia and provide data support and a theoretical foundation for the prevention and control of myopia. METHODS: Using a cross-sectional study and a comprehensive sampling survey, 34,138 students aged 5-19 years were screened for refraction in 22 primary and secondary schools in Langzhong, and 4000 behavioral questionnaires were delivered at random. After evaluation and rational problem-solving, a total of 3764 valid questionnaires were obtained. SPSS 23.0 statistical software was used for data analysis. RESULTS: The percentage of myopia among primary and secondary school students in Langzhong was 65.61%, with female students having a higher rate than male students ( P < 0.05); 52.81% of primary school students, 86.26% of secondary school students, and 88.17% of high school students had myopia. The incidence of myopia detection increased with school age ( P < 0.001), indicating a correlation between age and myopia prevalence. The prevalence of myopia was mainly low (40.53%) and moderate myopia (19.89%). The prevalence of high myopia (5.19%) was relatively high. The prevalence of myopia among female students (5.54%) was greater than that in male students ( P < 0.05) and increased with age ( P < 0.001). The proportion of students who wore eyeglasses was 24.36%, with a larger proportion of female students (25.93%) than male students (22.61%) ( P < 0.001). In addition, the rate of eyeglass use increased with school age ( P < 0.001). A logistic regression analysis revealed that higher grade point averages, female gender, and long-term usage of electronic items were risk factors for myopia. The results of the questionnaire survey revealed that students in this region were under immense pressure to perform well academically, spent a lot of time engaged in near-work activities, and had a low rate of myopia awareness; 24.43% of the students had not had a vision examination in the previous year, indicating that parents did not pay sufficient attention to eye health. CONCLUSION: The incidence of myopia among children and teenagers is high in Northeast Sichuan, and the outlook for addressing the problem is bleak. Therefore, it is critical to improve vision monitoring and eye health education.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Historical and contemporary management of infantile hemangiomas: a single-center experience.

Objective: This study explores the 22-year evolution of Infantile Hemangiomas (IHs) treatment strategies at a single-center hospital, aiming to establish an individualized IHs management protocol. Methods: Retrospective review of IHs infants 2000-2022 at the Department of Plastic Surgery, Jiangxi Provincial Children's Hospital. Results: In our study of 27,513 IHs cases, 72.2% were female, with the median age at first hospital visit being 25 days. The majority of cases had localized and superficial lesions primarily on the head, face, and neck (67.5%). Ulceration rates fell from 21.1% to 12.6% with the introduction of propranolol. Management strategies have shifted over time, with the proportion of cases undergoing expectant management dropping from 32.9% to 12.4%. Since 2008, 26.1% of patients were treated with oral propranolol, largely replacing corticosteroids. Topical ß-blockers have been used in 12.1% of cases, leading to a reduction in local injection therapy from 20.8% to 13.2%. Laser therapy, introduced in 2016, has been used in 13.8% of cases, while surgical excision has dropped from 25.0% to 8.5% due to alternative treatment options. Combination therapy was used in 8.8% of cases post-2015, indicating a rising trend. Drawing from the evolution of IHs management strategies, an individualized protocol for the management of IHs was successfully established. Conclusion: Treatment for IHs has evolved over recent decades, with less invasive medical interventions increasingly replacing more invasive methods. Furthermore, a personalized treatment protocol established in this study could boost the cure rate of IHs while minimizing potential side effects and complications.

Polychlorinated naphthalenes in freshwater fish from Beijing markets: Species-specific differences, effects of cooking, and health risk assessment.

Fish are an important source of human dietary exposure to polychlorinated naphthalenes (PCNs). The occurrence and sources of PCNs in different species of freshwater fish are unknown, and few studies have assessed human exposure risks to PCNs through freshwater fish. In this study, 140 freshwater fish samples from 10 species were collected from Beijing markets, China. The Σ75CNs concentration range in the fish was 20.7-1310 pg/g wet weight (ww). The highest median Σ75PCNs concentration (80.4 pg/g ww) was found in mandarin fish (Siniperca chuatsi), and the lowest (29.6 pg/g ww) in snakehead (Channa argus). Di- and tri-CNs were the dominant PCN homologues with contributions of 35.3 % and 30.8 %, respectively. Unintentionally produced PCNs from metal smelting might be the source of PCN contamination in freshwater fish. The cooking temperature and time did not significantly affect the PCN concentrations in fish or the PCN homologue profiles. The highest toxic equivalent (TEQ) value was observed in sturgeon (Acipenser sinensis), followed by mandarin fish. Hexa-CNs were the most abundant homologue for the PCN TEQs. A risk assessment indicated that the dietary exposure risks for local residents to PCNs through freshwater fish were low. However, the relatively high concentrations of PCNs in the samples deserve attention to avoid PCNs exposure risks for groups with high fish consumption rates. Furthermore, freshwater fish likely contain a mixture of contaminants including dioxin and furans which also display a similar mode of toxicity as the PCNs and could enhance the risk to fish consumers.

SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression.

OBJECTIVE: SUMO-specific protease 3 (SENP3), a member of the SUMO-specific protease family, reverses the SUMOylation of SUMO-2/3 conjugates. Dysregulation of SENP3 has been proven to be involved in the development of various tumors. However, its role in mantle cell lymphoma (MCL), a highly aggressive lymphoma, remains unclear. This study was aimed to elucidate the effect of SENP3 in MCL. METHODS: The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR, Western blotting or immunohistochemistry. MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs. Cell proliferation was assessed by CCK-8 assay, and cell apoptosis was determined by flow cytometry. mRNA sequencing (mRNA-seq) was used to investigate the underlying mechanism of SENP3 knockdown on MCL development. A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo. RESULTS: SENP3 was upregulated in MCL patient samples and cells. Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis. Meanwhile, the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown. Furthermore, the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model. CONCLUSION: SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

A preliminary study on short- and medium-chain chlorinated paraffins in duck farms: Concentrations, distribution, and dietary exposure risks.

Chlorinated paraffins (CPs) in poultry feed and the farm environment might bioaccumulate in poultry eggs. Unlike chickens, which are mostly raised in cages, ducks are commonly raised free range. This would expose ducks to CPs in the environment. However, information on the presence of CPs on duck farms is scarce. In the present study, samples of duck eggs, duck feathers, poultry feed, and soil were collected from 25 duck farms in South China. Forty-eight congener groups of short- and medium-chain CPs (SCCPs and MCCPs) were detected in the samples. Interestingly, relatively high concentrations of SCCPs and MCCPs were found in the duck feathers. The median concentrations of SCCPs and MCCPs in the duck eggs, feathers, feed and soil were: 46 and 18 ng/g wet weight, 2460 and 992 ng/g, 103 and 47 ng/g, and 24 and 10 ng/g dry weight, respectively. The dominant groups of SCCPs and MCCPs were C10Cl6-7 and C14Cl7-8, respectively. The close relationship between duck feathers and poultry feed indicated that the duck feathers might act as a bioindicator for the exposure of ducks to CPs. The margin of exposure approach was used to assess the health risk, with the results showing that the consumption of duck eggs posed a low risk to different age groups from exposure to SCCPs and MCCPs.

Rethinking orthographic neighbor in Chinese two-character word recognition: Insights from a megastudy.

The influence of orthographic neighbors on visual word recognition is well established in alphabetic scripts. To determine the universality of this effect across writing systems, researchers have been keen on exploring its presence and nature in Chinese word recognition. Given that Chinese is logographic, it necessitates a different definition for orthographic neighbors from the ones used in alphabetic scripts. One popular approach is to consider words that share characters as orthographic neighbors. Adopting this definition, a facilitative effect has been observed for characters that can create more words. However, as characters are also morphemes in Chinese, the facilitation found might actually come from a larger morphological family size. This possibility was tested in the present study by analyzing data from the Chinese Lexicon Project (CLP; Tse et al., Behavior Research Methods, 49, 1503-1519, 2017, Behavior Research Methods, 49, 1503-1519, 2022), a megastudy of two-character word recognition in traditional Chinese. If the effects of character-sharing are indeed morphological in nature, the facilitation should be smaller for ambiguous characters because the words formed are distributed over several morphological families. The results of the analyses were consistent with this hypothesis, revealing interactions between the number of words formed by a character and the number of meanings of the character. The implications of these findings were discussed in the context of definitions of orthographic neighbors and theories of word recognition in Chinese.

Analysis of cerebrospinal fluid metabolites affected by WenDanTang based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry.

WenDanTang (WDT) is a Chinese herbal formula used to treat various diseases, including neurodegenerative diseases. However, the neuroprotective metabolic pathways and the components involved in this process are not fully understood. In this study, we examined the neuroprotective metabolic pathways of WDT in rat brains using cerebrospinal fluid metabolomics and ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Twelve rats were randomly divided into a WDT (administrated with WDT solution) and a control group. The ultra-high-performance liquid chromatography technique was used to explore the components of the WDT solution and cerebrospinal fluid, and secondary mass spectra of cerebrospinal fluid were used to identify possible brain-incorporating components after WDT. The results of the differential metabolism analysis showed that eight metabolites were typically altered (all p < 0.05). By comparing the secondary mass spectra of the cerebrospinal fluid of rats and WDT solution, two possible brain-incorporating components of WDT, stachydrine and α-methoxyphenylacetic acid, were identified. The data also suggested that WDT affects nucleotide metabolism, glutathione metabolism, and B-vitamin metabolic pathways, the central differential metabolic pathways. These data suggest that WDT protects neurons through its active components, such as stachydrine, and regulates biochemical metabolism to affect the brain's energy metabolism and antioxidant capacity.

Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges.

Diabetes mellitus (DM) is a chronic and relentlessly progressive metabolic disease characterized by a relative or absolute deficiency of insulin in the body, leading to increased production of advanced glycosylation end products that further enhance oxidative and nitrosative stresses, often leading to multiple macrovascular (cardiovascular disease) and microvascular (e.g., diabetic nephropathy, diabetic retinopathy, and neuropathy) complications, representing the ninth leading cause of death worldwide. Existing medical treatments do not provide a complete cure for DM; thus, stem cell transplantation therapy has become the focus of research on DM and its complications. Urine-derived stem cells (USCs), which are isolated from fresh urine and have biological properties similar to those of mesenchymal stem cells (MSCs), were demonstrated to exert antiapoptotic, antifibrotic, anti-inflammatory, and proangiogenic effects through direct differentiation or paracrine mechanisms and potentially treat patients with DM. USCs also have the advantages of simple noninvasive sample collection procedures, minimal ethical issues, low cost, and easy cell isolation methods and thus have received more attention in regenerative therapies in recent years. This review outlines the biological properties of USCs and the research progress and current limitations of their role in DM and related complications. In summary, USCs have shown good versatility in treating hyperglycemia-impaired target organs in preclinical models, and many challenges remain in translating USC therapies to the clinic.

Automated pipeline for breast cancer diagnosis using US assisted diffuse optical tomography.

Ultrasound (US)-guided diffuse optical tomography (DOT) is a portable and non-invasive imaging modality for breast cancer diagnosis and treatment response monitoring. However, DOT data pre-processing and imaging reconstruction often require labor intensive manual processing which hampers real-time diagnosis. In this study, we aim at providing an automated US-assisted DOT pre-processing, imaging and diagnosis pipeline to achieve near real-time diagnosis. We have developed an automated DOT pre-processing method including motion detection, mismatch classification using deep-learning approach, and outlier removal. US-lesion information needed for DOT reconstruction was extracted by a semi-automated lesion segmentation approach combined with a US reading algorithm. A deep learning model was used to evaluate the quality of the reconstructed DOT images and a two-step deep-learning model developed earlier is implemented to provide final diagnosis based on US imaging features and DOT measurements and imaging results. The presented US-assisted DOT pipeline accurately processed the DOT measurements and reconstruction and reduced the procedure time to 2 to 3 minutes while maintained a comparable classification result with manually processed dataset.

Personality traits and peritoneal dialysis patients' prognosis.

Objective: Peritoneal dialysis (PD) requires high patient conscientiousness. Therefore, we aimed to investigate the relationship between conscientiousness score and prognosis in PD patients.Methods: The ten-item Big Five Personality Inventory's Chinese version was used to assess the conscientiousness score. Basic clinical information, prior medical history, hematological examination results, the occurrence of the first peritonitis and catheter-related infection, the start of hemodialysis, and the time of renal transplantation were collected. The patients were split into two groups, high and low conscientiousness groups, based on the mean value of the conscientiousness score. The differences in prognostic indicators were compared between groups, and the association between conscientiousness score and prognostic indicators in PD patients was assessed.Results: Enrolled PD patients were divided into low conscientiousness group 103 and high conscientiousness group 98. There were significant differences in serum albumin (p = 0.021) and iPTH (p = 0.045) between the two groups. Multivariate Cox regression analysis identified conscientiousness score as an independent risk factor for the development of first peritonitis (HR = 0.558, 95% CI 0.400-0.779, p = 0.001) and first catheter-related infection (HR = 0.544, 95% CI 0.308-0.962, p = 0.036) in PD patients. Conscientiousness score (HR = 2.377, 95% CI 1.109-5.095, p = 0.026) was independently associated with renal transplantation.Conclusion: Conscientiousness personality is closely related to the prognosis of PD patients.

The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells.

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.

Inhibition of GSDMD activation by Z-LLSD-FMK or Z-YVAD-FMK reduces vascular inflammation and atherosclerotic lesion development in ApoE-/- mice.

Pyroptosis is a form of pro-inflammatory cell death that can be mediated by gasdermin D (GSDMD) activation induced by inflammatory caspases such as caspase-1. Emerging evidence suggests that targeting GSDMD activation or pyroptosis may facilitate the reduction of vascular inflammation and atherosclerotic lesion development. The current study investigated the therapeutic effects of inhibition of GSDMD activation by the novel GSDMD inhibitor N-Benzyloxycarbonyl-Leu-Leu-Ser-Asp(OMe)-fluoromethylketone (Z-LLSD-FMK), the specific caspase-1 inhibitor N-Benzyloxycarbonyl-Tyr-Val-Ala-Asp(OMe)-fluoromethylketone (Z-YVAD-FMK), and a combination of both on atherosclerosis in ApoE-/- mice fed a western diet at 5 weeks of age, and further determined the efficacy of these polypeptide inhibitors in bone marrow-derived macrophages (BMDMs). In vivo studies there was plaque formation, GSDMD activation, and caspase-1 activation in aortas, which increased gradually from 6 to 18 weeks of age, and increased markedly at 14 and 18 weeks of age. ApoE-/- mice were administered Z-LLSD-FMK (200 µg/day), Z-YVAD-FMK (200 µg/day), a combination of both, or vehicle control intraperitoneally from 14 to 18 weeks of age. Treatment significantly reduced lesion formation, macrophage infiltration in lesions, protein levels of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, and pyroptosis-related proteins such as activated caspase-1, activated GSDMD, cleaved interleukin(IL)-1ß, and high mobility group box 1 in aortas. No overt differences in plasma lipid contents were detected. In vitro treatment with these polypeptide inhibitors dramatically decreased the percentage of propidium iodide-positive BMDMs, the release of lactate dehydrogenase and IL-1ß, and protein levels of pyroptosis-related proteins both in supernatants and cell lysates elevated by lipopolysaccharide + nigericin. Notably however, there were no significant differences in the above-mentioned results between the Z-LLSD-FMK group and the Z-YVAD-FMK group, and the combination of both did not yield enhanced effects. These findings indicate that suppression of GSDMD activation by Z-LLSD-FMK or Z-YVAD-FMK reduces vascular inflammation and lesion development in ApoE-/- mice.