Causal relationship between gut microbiota and thyroid nodules: a bidirectional two-sample Mendelian randomization study.

Objective: Emerging evidence suggests alterations in gut microbiota (GM) composition following thyroid nodules (TNs) development, yet the causal relationship remains unclear. Utilizing Mendelian Randomization (MR), this study aims to elucidate the causal dynamics between GM and TNs. Methods: Employing summary statistics from the MiBioGen consortium (n=18,340) and FinnGen consortium (1,634 TNs cases, 263,704 controls), we conducted univariable and multivariable MR analyses to explore the GM-TNs association. Techniques including inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO were utilized for causal inference. Instrumental variable heterogeneity was assessed through Cochran's Q statistic and leave-one-out analysis. Reverse MR was applied for taxa showing significant forward MR associations, with multivariate adjustments for confounders. Results: Our findings suggest that certain microbiota, identified as Ruminococcaceae_NK4A214_group (OR, 1.89; 95%CI, 0.47-7.64; p = 0.040), Senegalimassilia (OR, 1.72; 95%CI, 1.03-2.87; p =0.037), Lachnospiraceae (OR,0.64; 95%CI,0.41-0.99; p =0.045), exhibit a protective influence against TNs' development, indicated by negative causal associations. In contrast, microbiota categorized as Desulfovibrionales (OR, 0.63; 95%CI, 0.41-0.95; p =0.028), Prevotella_7 (OR, 0.79; 95%CI, 0.63-1.00; p =0.049), Faecalibacterium (OR, 0.66; 95%CI, 0.44-1.00; p =0.050), Desulfovibrionaceae (OR, 0.55; 95%CI, 0.35-0.86; p =0.008), Deltaproteobacteria (OR, 0.65; 95%CI, 0.43-0.97; p =0.036) are have a positive correlation with with TNs, suggesting they may serve as risk factors. Reverse MR analyses did not establish significant causal links. After comprehensive adjustment for confounders, taxa Desulfovibrionales (Order), Desulfovibrionaceae (Family), Deltaproteobacteria (Class) remain implicated as potential contributors to TNs' risk. Discussion: This study substantiates a significant causal link between GM composition and TNs development, underscoring the thyroid-gut axis's relevance. The findings advocate for the integration of GM profiles in TNs' prevention and management, offering a foundation for future research in this domain.

Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk.

Background: There is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer. Methods: We performed a MR analysis of the data from the genome-wide association study (GWAS) of European ancestry to evaluate the independent effects of three reproductive behaviors on lung cancer overall (LUCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). We mainly used the inverse-variance weighting method for the MR analysis. Sensitivity was determined by a MR-pleiotropy residual sum and outlier analysis, a weighted median analysis, a MR-Egger analysis, and a leave-one-out analysis. Results: The MR analysis results revealed that older AFS had a causal relationship with LUCA [odds ratio (OR) =0.6283, 95% confidence interval (CI): 0.4959-0.7961, P=0.0001), LUAD (OR =0.7042, 95% CI: 0.4967-0.9984, P=0.049), and LUSC (OR =0.6231, 95% CI: 0.4386-0.8853, P=0.0083). Conclusions: Our results revealed a causal relationship between older AFS and a lower risk of lung cancer. Our findings emphasize the importance of providing sex education, as early sexual intercourse may have undesirable effects. In addition, early psychological treatment is also essential.

A high oxidase-like activity, bimetallic single-atom nanozyme FeCe/NC prepared by FeCe-ZIF-8 approach for sensing tannic acid in tea.

To improve the activity of single-atom nanozymes (SAzymes) for applications in food analysis, a new bimetal SAzyme FeCe/NC was developed. Its oxidase-like activity is 40% higher than that of single metal SAzyme Fe/NC. Based on a series of characterization investigations, the catalytic mechanism is that it directly catalyzed O2 to generate •OH, O2 •-and 1O2. It could directly catalyze oxidation 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxTMB, thereunder, a FeCe/NC SAzyme-TMB colorimetric method for the detection of tannic acid (TA) was constructed after the optimization of catalytic conditions. The method has a high R2 of 0.995, a low limit of detection (LOD) of 0.26 µmol/L, and high stability. The detection performance was validated by the real samples (tea). Therefore, the prepared bimetallic SAzyme FeCe/NC can be applied for TA detection without the addition of H2O2, and will have broad applications in the areas of food, feed, and life science.

In Vivo Detection of Abscisic Acid in Tomato Leaves Based on a Disposable Stainless Steel Electrochemical Immunosensor.

Abscisic acid (ABA) plays an important regulatory role in plants. It is very critical to obtain the dynamic changes of ABA in situ for botanical research. Herein, coupled with paper-based analysis devices, electrochemical immunoelectrodes based on disposable stainless steels sheet were developed for ABA detection in plants in situ. The stainless steel sheets were modified with carbon cement, ferrocene-graphene oxide-multi walled carbon nanotubes nanocomposites, and ABA antibodies. The system can detect the ABA in the range of 1 nM to 100 µM, with a limit of detection of 100 pM. The ABA content in tomato leaves under high salinity was detected in situ. The trend of ABA changes was similar to the expression of SlNCED1 and SlNCED2. Overall, this study offers an approach for in situ detection of ABA in plants, which will help to study the regulation mechanism of ABA in plants and to promote the development of precision agriculture.

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.

Pulmonary embolism in patients with chronic coronary syndrome masquerading as acute coronary syndrome: a case report and literature review.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

MYB4 in Lilium pumilum affects plant saline-alkaline tolerance.

Lilium pumilum DC (L. pumilum DC) plays an important role in the rational utilization of salinized soil. To explore the molecular mechanism of salt-tolerant L. pumilum, the LpMYB4 was cloned. LpMYB4 close relationship with Bambusa emeiensis and Zea mays MYB4 throughout the phylogenetic tree construction. LpMYB4 protein was found to be localized in the nucleus. Prokaryotic and eukaryotic bacterial solution resistance experiments proved that the exogenous introduction of LpMYB4 made the overexpression strains obtain better survival ability under saline-alkaline stress. Compared with wild-type plants, tobacco plants overexpressing LpMYB4 had better growth and lower leaf wilting and lodging, the content of chlorophyll was higher, the content of hydrogen peroxide and superoxide anion was lower, the activity of peroxidase and superoxide dismutase was higher and the relative conductivity was lower under saline-alkaline stress. The analysis of seed germination and seedling resistance of transgenic plants under salt stress showed that LpMYB4 transgenic seeds were more tolerant to salt stress during germination and growth. Yeast two-hybrid and two-luciferase complementation experiments showed that LpMYB4 interacted with yeast two-hybrid and LpGPX6. The analysis of the role of LpMYB4 in improving plant saline-alkali resistance is helpful to the transformation of plant germplasm resources and has great significance for agriculture and sustainable development.

Oxygen Vacancy Piezoelectric Nanosheets Constructed by a Photoetching Strategy for Ultrasound "Unlocked" Tumor Synergistic Therapy.

Piezoelectric dynamic therapy (PzDT) is an effective method of tumor treatment by using piezoelectric polarization to generate reactive oxygen species. In this paper, two-dimensional Cu-doped BiOCl nanosheets with surface vacancies are produced by the photoetching strategy. Under ultrasound, a built-in electric field is generated to promote the electron and hole separation. The separated carriers achieve O2 reduction and GSH oxidation, inducing oxidative stress. The bandgap of BiOCl is narrowed by introducing surface oxygen vacancies, which act as charge traps and facilitate the electron and hole separation. Meanwhile, Cu doping induces chemodynamic therapy and depletes GSH via the transformation from Cu(II) to Cu(I). Both in vivo and in vitro results confirmed that oxidative stress can be enhanced by exogenous ultrasound stimulation, which can cause severe damage to tumor cells. This work emphasizes the efficient strategy of doping engineering and defect engineering for US-activated PzDT under exogenous stimulation.

Efficacy, safety, and immunogenicity of SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012: a randomized, double-blind, placebo-controlled phase 3 trial.

Background: We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China. Methods: This is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention. Results: 2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals. Conclusion: The LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period. Clinical trial registration: ClinicalTrials.gov, identifier NCT05745545.

Analysis of related factors and treatment effect of chylothorax after lung surgery.

Background: Chylothorax is a seldom encountered complication following lung surgery. However, due to the widespread practice of lung surgery, postoperative complications have inevitably arisen. Chylothorax significantly affects a patient's discharge and recovery. This study investigates the risk factors for postoperative chylothorax at our center and analyzes various treatment modalities and prognostic outcomes. Methods: A retrospective analysis was conducted on all postoperative lung resections performed between January 2018 to August 2021 that met the inclusion criteria. Inclusion criteria covered patients undergoing various thoracic surgeries for lung conditions, while exclusion criteria included postoperative referrals for surgeries unrelated to lung tumors. Results: Postoperative chylothorax occurred in 42 of 5,706 patients after lung surgery. General information and disease-related data of the chylothorax and control group were analyzed by univariate and multivariate analyses. Multivariate analysis showed that serum albumin before surgery [odds ratio (OR) =0.86, 95% confidence interval (CI): 0.81-0.91, P<0.001], γ-glutamyl transferase level before surgery (after logarithmic transformation, OR =1.01, 95% CI: 1.00-1.01, P=0.01), squamous cell carcinoma (OR =2.77, 95% CI: 1.37-5.6, P=0.008), right mediastinal lymph node dissection (OR =3.15, 95% CI: 1.62-6.14, P<0.001) were independent risk factors for postoperative chylothorax. Among the 42 cases of postoperative chylothorax, 26 patients were improved with conservative treatments, and 6 patients were improved with chemical pleurodesis. Eight patients with postoperative chylothorax underwent thoracoscopic thoracic duct ligation. Three patients experienced severe postoperative complications: one was discharged after prolonged treatment, while the remaining two either succumbed or were discharged against medical advice. Conclusions: The incidence of chylothorax after lung surgery closely correlates with the intraoperative trauma and nutritional status of patients during the perioperative period. The majority of patients with postoperative chylothorax experienced relief through conservative measures, somatostatin administration, and chemical pleurodesis. Nevertheless, substantial postoperative chylothorax necessitated surgical intervention, involving thoracic duct ligation or drug pleurodesis.

Clinical features and molecular landscape of cuproptosis signature-related molecular subtype in gastric cancer.

Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis-related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model-based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature-based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS-High and CSRS-Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS-High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS-Low subtype. Patients with CSRS-Low score were characterized by prolonged survival time. Further analysis indicated that CSRS-Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS-High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS-Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS-High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature-based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

Brucellosis-induced peritonitis and abdominal aortitis in a non-endemic area patient on peritoneal dialysis: a case report and literature review.

Background: Brucella infection is uncommon among peritoneal dialysis (PD) patients in non-endemic areas, and the occurrence of both peritonitis and abdominal aortitis is rare. Case presentation: In December 2023, a 63-year-old male patient undergoing PD was admitted to Shaoxing Second Hospital due to fever, abdominal pain, and cloudy dialysate. Upon physical examination, diffuse mild abdominal pain and tenderness were observed. Subsequent investigation into the patient's medical history revealed consumption of freshly slaughtered lamb from local farmers 3 days prior to the onset of symptoms. Various diagnostic tests, including routine blood tests, procalcitonin levels, and PD fluid analysis, indicated the presence of infection. Abdominal computed tomography (CT) imaging revealed localized lumen widening of the abdominal aorta with surrounding exudative changes. On the sixth day in the hospital, blood and PD fluid cultures confirmed Brucella melitensis infection. The patient was diagnosed with brucella-associated peritonitis and aortitis. Treatment was adjusted to include rifampin and doxycycline for 6 weeks, and the decision was made to keep the PD catheter. Remarkably, the patient exhibited resolution of peritonitis and abdominal aortitis within the initial week of the adjusted treatment. Currently, the patient continues to receive ongoing clinical monitoring. Conclusion: Brucella is rare but can cause PD-associated peritonitis and arteritis. Prompt diagnosis and treatment can lead to a good outcome in PD patients. Dual therapy is effective, but the need for catheter removal is unclear. Consider international guidelines and patient factors when deciding on catheter removal.

Thrombo-inflammatory prognostic score can predict the outcome of stroke: a retrospective cohort study.

Introduction: Inflammatory and thrombotic biomarkers are simple prognostic indicators of adverse clinical outcomes in patients with ischemic stroke (IS). However, isolated assessment of inflammatory or thrombus biomarkers in patients with IS is limited in clinical practice. Methods: This study aimed to evaluate the predictive value of a novel, simplified thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of IS and to identify high-risk patients at the time of admission. The study population comprised 915 patients with a primary diagnosis of IS in the emergency departments of five grade A tertiary hospitals in China. Results: Patients were divided into two groups based on the modified Rankin Scale (mRS): <3 and ≥3. TIPS with a value of "2" indicates biomarkers for high inflammation and thrombosis, "1" represents a biomarker, and "0" signals the absence of a biomarker. Multivariate logistic regression analysis was employed to identify the association between TIPS and clinical outcomes. TIPS was an independent predictor of unfavorable functional outcomes and mortality. It had a superior predictive value for clinical outcomes compared to the National Institutes of Health Stroke Scale (NIHSS) (effect ratio, 37.5%), D-dimer (effect ratio, 12.5%), and neutrophil-to-lymphocyte ratio (effect ratio, 25%). Conclusion: The survival probability of TIPS with a score of 0 is twice as high as that of TIPS with a score of 2. The survival rate for TIPS with a score of 1 is one time higher than that for TIPS with a score of 2. The predictive value of TIPS for unfavorable functional outcomes is represented by an AUC of 0.653. TIPS is associated with an increased risk of death and unfavorable functional outcomes in patients with IS and may be a useful tool for identifying high-risk patients at the time of admission.

Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

A linear validation method of analytical procedures based on the double logarithm function linear fitting.

BACKGROUND: The ICH Q2(R1) guideline defines linearity as its ability to obtain test results which are directly proportional to the concentration of the analyte. However, the coefficient of determination typically used is limited to evaluating the response function rather than the linearity of results, the current guidelines fail to provide a method for assessing the linearity of results. RESULTS: The paper presents a data analysis method to validate the linearity of results. The method demonstrates the degree of data proportionality by applying double logarithm function linear fitting and solves the problem of setting the acceptance criterion by investigating the relationship between the slope, working range ratio, and maximum error ratio. In principle, this method has advantages over the coefficient of variation and recovery rate recommended by the ICH M10 guideline. Moreover, the relative error data show that the double logarithm function is more effective in overcoming heteroscedasticity than straight-line fitting. SIGNIFICANCE: This method is more consistent with the linear definition outlined in ICH Q2 guidelines and has the potential to further clarify the concept and validation method of linearity in the future.

Establishment of XRD fourier fingerprint identification method of realgar decoction pieces and its anti-tumor activity in tumor-in-situ transplanted mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control. AIM OF THE STUDY: The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed. MATERIALS AND METHODS: Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed. RESULT: The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits. CONCLUSION: The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.

Virtual Photon-Mediated Quantum State Transfer and Remote Entanglement between Spin Qubits in Quantum Dots Using Superadiabatic Pulses.

Spin qubits in semiconductor quantum dots are an attractive candidate for scalable quantum information processing. Reliable quantum state transfer and entanglement between spatially separated spin qubits is a highly desirable but challenging goal. Here, we propose a fast and high-fidelity quantum state transfer scheme for two spin qubits mediated by virtual microwave photons. Our general strategy involves using a superadiabatic pulse to eliminate non-adiabatic transitions, without the need for increased control complexity. We show that arbitrary quantum state transfer can be achieved with a fidelity of 95.1% within a 60 ns short time under realistic parameter conditions. We also demonstrate the robustness of this scheme to experimental imperfections and environmental noises. Furthermore, this scheme can be directly applied to the generation of a remote Bell entangled state with a fidelity as high as 97.6%. These results pave the way for fault-tolerant quantum computation on spin quantum network architecture platforms.

A composite hydrogel loaded with the processed pyritum promotes bone repair via stimulate the osteogenic differentiation of BMSCs.

Tissue engineering shows promise in repairing extensive bone defects. The promotion of proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by biological scaffolds has a significant impact on bone regeneration outcomes. In this study we used an injectable hydrogel, known as aminated mesoporous silica gel composite hydrogel (MSNs-NH2@GelMA), loaded with a natural drug, processed pyritum (PP), to promote healing of bone defects. The mechanical properties of the composite hydrogel were significantly superior to those of the blank hydrogel. In vitro experiments revealed that the composite hydrogel stimulated the osteogenic differentiation of BMSCs, and significantly increased the expression of type I collagen (Col 1), runt-related transcription factor 2 (Runx 2), alkaline phosphatase (ALP), osteocalcin (OCN). In vivo experiments showed that the composite hydrogel promoted the generation of new bones. These findings provide evidence that the composite hydrogel pyritum-loaded holds promise as a biomaterial for bone repair.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study.

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

Antiphospholipid antibodies and the risk of adverse pregnancy outcomes in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). METHODS: Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. RESULTS: There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiß2GP1) positivity had an increased risk of fetal loss. CONCLUSIONS: Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiß2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth.PROSPERO (CRD42023388122).