Physiologically-based pharmacokinetic/pharmacodynamic modeling of meropenem in critically ill patients.

This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic model (PBPK/PD) of meropenem for critically ill patients. A PBPK model of meropenem in healthy adults was established using PK-Sim software and subsequently extrapolated to critically ill patients based on anatomic and physiological parameters. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of pharmacokinetic parameters Cmax, AUC0-∞, and CL to evaluate the accuracy of the PBPK model. The model was verified using meropenem plasma samples obtained from Intensive Care Unit (ICU) patients, which were determined by HPLC-MS/MS. After that, the PBPK model was combined with a PKPD model, which was developed based on f%T > MIC. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients. The developed PBPK model successfully predicted the meropenem disposition in critically ill patients, wherein the MFE average and GMFE of all predicted PK parameters were within the 1.25-fold error range. The therapeutic drug monitoring (TDM) of meropenem was conducted with 92 blood samples from 31 ICU patients, of which 71 (77.17%) blood samples were consistent with the simulated value. The TDM results showed that meropenem PBPK modeling is well simulated in critically ill patients. Monte Carlo simulations showed that extended infusion and frequent administration were necessary to achieve curative effect for critically ill patients, whereas excessive infusion time (> 4 h) was unnecessary. The PBPK/PD modeling incorporating literature and prospective study data can predict meropenem pharmacokinetics in critically ill patients correctly. Our study provides a reference for dose adjustment in critically ill patients.

Covered stent combined with embolization treatment for complex congenital lower limb arteriovenous malformations: case report and literature review.

BACKGROUND: Currently, the treatment outcomes for complex congenital arteriovenous malformations (AVMs) remain unsatisfactory. This article reports on the utilization of an abdominal aortic stent graft, in conjunction with embolization techniques, for managing acute heart failure triggered by complex congenital arteriovenous malformations in the lower limb. CASE PRESENTATION: We present a case involving a patient with congenital AVMs in the lower limb, who had suffered from prolonged swelling in the left lower limb and recently developed symptoms of heart failure. At the age of 67, the patient was definitively diagnosed with a complex congenital AVMs in the lower limb. This article delves into the practical experiences and limitations encountered in employing an abdominal aortic stent graft, coupled with embolization, to address acute heart failure caused by complex congenital AVMs in the lower limb. CONCLUSIONS: Our article presents the initial report on the challenges and limitations encountered in treating acute heart failure triggered by complex congenital AVMs in the lower limb, utilizing a combination of abdominal aortic stent graft placement and embolization techniques.

Comparison of one-year outcomes and quality of life between radiofrequency ablation and microwave ablation in the treatment of lower extremity varicose veins: A retrospective cohort study.

OBJECTIVE: This study compared the outcomes of radiofrequency ablation (RFA) and microwave ablation (EMA) for treating lower limb varicose veins. METHODS: Patients who underwent RFA (n = 240) or EMA (n = 209) at our institute from December 2020 to August 2022 were included in this retrospective investigation. Follow-up outcomes included active vein occlusion rate, Venous Clinical Severity Score (VCSS), the Aberdeen Varicose Vein Questionnaire (AVVQ), and Chronic Insufficiency Venous Quality of Life questionnaire-14 (CIVIQ-14)score. RESULTS: There was no significant difference in the active vein occlusion rate between the two groups after the operation (p > .05). Compared to pre-surgery scores, both groups showed substantial improvement in VCSS, AVVQ, and CIVIQ-14 scores(p < .05), there was no significant difference in these scores in either group (p > .05). CONCLUSION: Intravenous radiofrequency and microwave ablation effectively improve the quality of life for patients with lower limb varicose veins, with low post-operative complication and recurrence rates.

Incomplete histologic healing and diminished biomechanical strength of meniscus-bone interface after medial meniscus posterior root transosseous repair in a goat model.

PURPOSE: To enhance the understanding of histological healing after repairing medial meniscal posterior root tear (MMPRT) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling thirty-six knee joints, were allocated into three groups (n = 12): Sham group (Sham), Root Tear group (RT), and Root Tear with Transosseous Suture group (RTS). At 12- and 24-week intervals post-surgery, all the knees were harvested for imaging, macroscopic, histological, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface which connected the tibial and the circular fibers of the meniscus, with a bony insertion and a root-meniscus transition. A direct-fibrous-connection displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect-fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs. 0.19 ± 0.02, P = 0.0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = 0.0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSION: The incomplete healing may be attributed to the histological factors underlying the low healing rate and persistent MME. Notably, the region attached to the posterior-cruciate-ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to particularly enhance the healing of the root-meniscus transition.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Hydroxyl carboxylate anion catalyzed depolymerization of biopolyesters and transformation to chemicals.

Upcycling biopolyesters (e.g., polyglycolic acid, PGA) into chemicals is an interesting and challenging topic. Herein, we report a novel protocol to upgrade biopolyesters derived from hydroxyl carboxylic acids over ionic liquids with a hydroxyl carboxylate anion (e.g., glycolate, lactate) into various chemicals under metal-free conditions. It is found that as hydrogen-bond donors and acceptors, hydroxyl carboxylate anions can readily activate the ester group via hydrogen bonding and decompose biopolyesters via autocatalyzed-transesterification to form hydroxyl carboxylate anion-based intermediates. These intermediates can react with various nucleophiles (e.g. H2O, methanol, amines and hydrazine) to access the corresponding acids, esters and amides under mild conditions (e.g., 40 °C). For example, 1-ethyl-3-methylimidazolium glycolate can achieve complete transformation of PGA into various chemicals such as glycolic acid, alkyl glycolates, 2-hydroxy amides, 2-(hydroxymethyl)benzimidazole, and 1,3-benzothiazol-2-ylmethanol in excellent yields via hydrolysis, alcoholysis and aminolysis, respectively. This protocol is simple, green, and highly efficient, which opens a novel way to upcycle biopolyesters to useful chemicals.

Tobacco crop rotation enhances the stability and complexity of microbial networks.

Introduction: The effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities. Methods: In order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach. Results: There was no significant difference in α diversity, but significant difference in ß diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable. Discussion: From this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .

PI3K/AKT/mTOR signaling regulates BCP ceramic-induced osteogenesis.

An increasing number of studies demonstrate that biphasic calcium phosphate (BCP) ceramics can induce bone regeneration. However, the underlying molecular mechanisms involved are still poorly understood. This work was proposed to investigate how PI3K/AKT/mTOR signaling influenced the osteogenesis mediated by BCP ceramics. The results showed that incubation with BCP ceramics promoted the proliferation of murine bone marrow-derived mesenchymal stem cells (BMSCs) in a time-dependent manner. The resulting cell proliferation was then suppressed by the selective inhibition of either PI3K, AKT, or mTOR signaling activation. Next, we confirmed that BCP ceramics up-regulated the phosphorylation levels of AKT and mTOR in BMSCs, suggesting the ability of BCP ceramics to drive the activation of PI3K/AKT/mTOR signaling in BMSCs. Furthermore, the blockade of PI3K/AKT/mTOR signaling prevented BCP ceramics-induced osteogenic differentiation and pro-angiogenesis of BMSCs by down-regulating the expression of genes encoding OPN, RUNX2 or VEGF. Moreover, the PI3K/AKT/mTOR signaling blockade suppressed stem cell infiltration and new bone formation in the implants following intra-muscular implantation of BCP ceramics in mice. Therefore, our results suggested that PI3K/AKT/mTOR signaling played a critical regulatory role in BCP ceramic-induced osteogenesis.

Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.

Mitotic catastrophe (MC), which occurs under dysregulated mitosis, represents a fascinating tactic to specifically eradicate tumor cells. Whether pyroptosis can be a death form of MC remains unknown. Proteasome-mediated protein degradation is crucial for M-phase. Bortezomib (BTZ), which inhibits the 20S catalytic particle of proteasome, is approved to treat multiple myeloma and mantle cell lymphoma, but not solid tumors due to primary resistance. To date, whether and how proteasome inhibitor affected the fates of cells in M-phase remains unexplored. Here, we show that BTZ treatment, or silencing of PSMC5, a subunit of 19S regulatory particle of proteasome, causes G2- and M-phase arrest, multi-polar spindle formation, and consequent caspase-3/GSDME-mediated pyroptosis in M-phase (designated as mitotic pyroptosis). Further investigations reveal that inhibitor of WEE1/PKMYT1 (PD0166285), but not inhibitor of ATR, CHK1 or CHK2, abrogates the BTZ-induced G2-phase arrest, thus exacerbates the BTZ-induced mitotic arrest and pyroptosis. Combined BTZ and PD0166285 treatment (named BP-Combo) selectively kills various types of solid tumor cells, and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 monotreatment. Studies using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment, and no obvious toxicity is observed in BP-Combo-treated mice. These findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase, characterize pyroptosis as a new death form of mitotic catastrophe, and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

Creating and characteristics of a novel biomacromolecules complex of pea protein isolated-tannic acid-magnesium ion.

Pea protein isolate (PPI) was used as a carrier matrix to load tannic acid (TA) due to its multiple cavity structures and reaction sites, after that, magnesium ion (M) was further added to form more stable carrier structures. PPI was covalently bound with TA to form TA-PPI complexes in alkaline conditions, then M induced the aggregation of TA-PPI to produce M-TA-PPI complexes. TA mainly interacted with free amino groups and sulfhydryl groups of PPI, thereby decreasing their content in complexes. TA further decreased the α-helix content and increased the ß-sheet and ß-turn content in TA-PPI complexes correspondingly, nevertheless the M would decline these changes in M-TA-PPI complexes. As a result of binding, TA and M jointly increased the average molecular size of complexes. The higher TA addition amount (10-20 mg/g PPI) was conducive to the stronger intramolecular interactions (more hydrophobic interactions and disulfide bonds), gel structure (higher hardness value) and storage modulus in M-TA-PPI gels. Compared with TA-PPI complexes, M-TA-PPI complexes showed higher stability in gastric digestion and higher TA releasement and antioxidant capacity of its digesta in intestinal digestion. This kind of metal-phenolics-protein complexes may have potentials to be a stable and efficient carrier for loading gastric sensitive polyphenols.

Core-shell structured alginate-based hydrogel beads modified by starch and protocatechuic acid: Preparation, characterization, phenolic slow release and stable antioxidant potential.

A novel core-shell structured alginate-based hydrogel bead modified by co-gelatinizing with starch and protocatechuic acid (PA), was designed to modulate physical properties of beads, release behavior and antioxidant stability of encapsulated bioactives. Core was fabricated by ionotropic gelation, and its formulation (ratio of sodium alginate/starch) was determined by particle size/starch distribution, texture and bioactive encapsulation capacity of core. Then, coating core with shell-forming solution co-gelatinized with different doses of PA, and subsequently cross-linked with Ca2+ to obtain core-shell structured beads. Surface microstructure, mechanical characteristics, and swelling ratio of beads were affected by concentrations of PA. Besides, core-shell structure containing PA could enhance delivery and sustained release of encapsulated phenolic bioactives during in vitro digestion, and improve their antioxidant potential stability. Furthermore, interaction between PA and polysaccharide components was elucidated by FTIR and TGA. The present information was beneficial for the advancement of functional food materials and bioactive delivery systems.

Advancements in diabetic foot insoles: a comprehensive review of design, manufacturing, and performance evaluation.

The escalating prevalence of diabetes has accentuated the significance of addressing the associated diabetic foot problem as a major public health concern. Effectively offloading plantar pressure stands out as a crucial factor in preventing diabetic foot complications. This review comprehensively examines the design, manufacturing, and evaluation strategies employed in the development of diabetic foot insoles. Furthermore, it offers innovative insights and guidance for enhancing their performance and facilitating clinical applications. Insoles designed with total contact customization, utilizing softer and highly absorbent materials, as well as incorporating elliptical porous structures or triply periodic minimal surface structures, prove to be more adept at preventing diabetic foot complications. Fused Deposition Modeling is commonly employed for manufacturing; however, due to limitations in printing complex structures, Selective Laser Sintering is recommended for intricate insole designs. Preceding clinical implementation, in silico and in vitro testing methodologies play a crucial role in thoroughly evaluating the pressure-offloading efficacy of these insoles. Future research directions include advancing inverse design through machine learning, exploring topology optimization for lightweight solutions, integrating flexible sensor configurations, and innovating new skin-like materials tailored for diabetic foot insoles. These endeavors aim to further propel the development and effectiveness of diabetic foot management strategies. Future research avenues should explore inverse design methodologies based on machine learning, topology optimization for lightweight structures, the integration of flexible sensors, and the development of novel skin-like materials specifically tailored for diabetic foot insoles. Advancements in these areas hold promise for further enhancing the effectiveness and applicability of diabetic foot prevention measures.

Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and in vitro experiments.

5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through in vitro experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in In vitro experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.

Mn(I)-Catalyzed Carbon-Skeleton Rearrangement of Tertiary Alcohol-Based Aldol Reaction with Aldehydes.

A Mn-catalyzed ligand-directed Csp3-Csp2 coupling of tertiary allylic alcohols with arylaldehydes has been developed. The method provides an efficient approach to access 1,5-diarylpent-1-en-3-ones via carbon-skeleton rearrangement-based aldol reaction.

Recommendations for managing adult acne and adolescent acne based on an epidemiological study conducted in China.

There are numerous differences between adult acne and adolescent acne in terms of causes, distribution, and characteristics of skin lesions, as well as treatment. This paper aims to summarize the differences between adult and adolescent acne in China, in order to propose more suitable ways to improve their quality of life. We collected basic information, acne-related information, acne-affecting factors, quality of life scores and treatment-related information of acne patients. A total of 552 questionnaires were collected. Adult acne is typically predominant on the cheeks, similar to adolescent acne, with a relatively lower incidence in other areas, apart from the jawline. Pigmentation and depressed scars are present in nearly half of acne patients, while hypertrophic scars are less frequently observed. Teenagers often have a higher consumption of dairy products, sugary drinks, and high-sugar and high-fat foods. Eczema is more common in adult acne. Additionally, more adults than teenagers experience stress and poor quality of life related to acne. Adolescents are more likely to seek treatment online and on social media. Clinicians must thoroughly evaluate diverse risk factors and formulate personalized acne management strategies for patients with different types of acne.

Automatic Classification and Segmentation of Multiclass Jaw Lesions in Cone-Beam Computed Tomography using Deep Learning.

OBJECTIVES: To develop and validate a modified deep learning (DL) model based on nnU-net for classifying and segmenting five-class jaw lesions using cone-beam computed tomography (CBCT). METHODS: A total of 368 CBCT scans (37 168 slices) were used to train a multi-class segmentation model. The data underwent manual annotation by two oral and maxillofacial surgeons (OMSs) to serve as ground truth. Sensitivity, specificity, precision, F1-score, and accuracy were used to evaluate the classification ability of the model and doctors, with or without artificial intelligence assistance. The dice similarity coefficient (DSC), average symmetric surface distance (ASSD) and segmentation time were used to evaluate the segmentation effect of the model. RESULTS: The model achieved the dual task of classifying and segmenting jaw lesions in CBCT. For classification, the sensitivity, specificity, precision, and accuracy of the model were 0.871, 0.974, 0.874 and 0.891, respectively, surpassing oral and maxillofacial radiologists (OMFRs) and OMSs, approaching the specialist. With the model's assistance, the classification performance of OMFRs and OMSs improved, particularly for odontogenic keratocyst (OKC) and ameloblastoma (AM), with F1-score improvements ranging from 6.2% to 12.7%. For segmentation, the DSC was 87.2% and the ASSD was 1.359 mm. The model's average segmentation time was 40 ± 9.9 s, contrasting with 25 ± 7.2 min for OMSs. CONCLUSIONS: The proposed DL model accurately and efficiently classified and segmented five classes of jaw lesions using CBCT. In addition, it could assist doctors in improving classification accuracy and segmentation efficiency, particularly in distinguishing confusing lesions (e.g., AM and OKC).

Influence of Polypropylene Fiber on Concrete Permeability under Freeze-Thaw Conditions and Mechanical Loading.

Polypropylene fiber reinforcement is an effective method to enhance the durability of concrete structures. With the increasing public interest in the widespread use of polypropylene fiber reinforced concrete (PFRC), the necessity of evaluating the mechanism of polypropylene fiber (PF) on the permeability of concrete has become prominent. This paper describes the influence of PF on the concrete permeability exposed to freeze-thaw cycles under compressive and tensile stress. The permeability of PFRC under compressive and tensile loads is accurately measured by a specialized permeability setup. The permeability of PFRC under compressive and tensile loads, the volume change of PFRC under compressive load, and the relationship between compressive stress levels at minimum permeability and minimum volume points of PFRC are discussed. The results indicate that the addition of PF adversely affects the permeability of concrete without freeze-thaw damage and cracks. However, it decreases the permeability of concrete specimens exposed to freeze-thaw cycles and cracking. Under compressive load, the permeability of PFRC initially decreases slowly and follows by a significant increase as the compressive stress level increases. This phenomenon correlates with the volume change of the specimen. The compressive stress level of the minimum permeability point and compressive stress level of the minimum volume point of PFRC exhibit a linear correlation, with a fitted proportional function parameter γ ≈ 0.98872. Under tensile load, the permeability of PFRC increases gradually with radial deformation and follows by a significant increase. The strain-permeability curves of PFRC under loading are studied and consist of two stages. In stage I, the permeability of PFRC gradually decreases with the increase of strain under compressive load, while the permeability increases with the increase of strain under tensile load. In stage II, under compressive load, the permeability of PFRC increases with the increase of freeze-thaw cycles, whereas under tensile load, the permeability gradually decreases with the increase of freeze-thaw cycles. The reduction of PF on the permeability of PFRC under tensile load is greater than that under compressive load. In future research, the relationship between strain and permeability of PFRC can be integrated with its constitutive relationship between stress and strain to provide a reference for the application of PF in the waterproofing of concrete structures.

Associations between deep venous thrombosis and thyroid diseases: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach. METHODS: This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran's Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes. RESULTS: This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran's Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods. CONCLUSIONS: This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.