Association of circulating vitamin levels with thyroid diseases: a Mendelian randomization study

BackgroundPrevious observational studies have shown conflicting results of vitamins supplementation for thyroid diseases. The causal relationships between vitamins and thyroid diseases are unclear. Therefore, we conducted a two-sample bidirectional Mendelian randomization (MR) study to explore association of circulating vitamin levels with thyroid diseases.MethodsWe performed a bidirectional MR analysis using genome-wide association study (GWAS) data. Genetic tool variables for circulating vitamin levels include vitamins A, B9, B12, C, D, and E, Genetic tool variables of thyroid diseases include autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid nodules (TNs), and Thyroid cancer (TC). Inverse-variance weighted multiplicative random effects (IVW-RE) was mainly used for MR Analysis, weighted median (WM) and MR Egger were used as supplementary methods to evaluate the relationships between circulating vitamin levels and thyroid diseases. Sensitivity and pluripotency were evaluated by Cochran’s Q test, MR-PRESSO, Radial MR, MR-Egger regression and leave-one-out analysis.ResultsPositive MR evidence suggested that circulating vitamin C level is a protective factor in autoimmune hypothyroidism (ORIVW-RE=0.69, 95%CI: 0.58-0.83, p = 1.05E-04). Reverse MR Evidence showed that genetic susceptibility to autoimmune hyperthyroidism is associated with reduced level of circulating vitamin A(ORIVW-RE = 0.97, 95% CI: 0.95–1.00, p = 4.38E-02), genetic susceptibility of TNs was associated with an increased level of circulating vitamin D (ORIVW-RE = 1.02, 95% CI: 1.00–1.03, p = 6.86E-03). No causal and reverse causal relationship was detected between other circulating vitamin levels and thyroid diseases.ConclusionOur findings provide genetic evidence supporting a bi-directional causal relationship between circulating vitamin levels and thyroid diseases. These findings provide information for the clinical application of vitamins prevention and treatment of thyroid diseases

Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials

ObjectiveResearch data suggests that ultrasound-assisted wound debridement (UAWD) can effectively promote the healing of diabetic foot ulcers (DFU). However, existing research is not consistent with this viewpoint. Therefore, we conducted this study to investigate the effect of UAWD on the healing of diabetic foot ulcers.MethodsFrom the establishment of the database to January 2024, we searched 8 databases to study the effectiveness and safety of UAWD in the treatment of DFU. Two authors independently screened the qualifications of the articles, while two authors extracted relevant data. Statistical analysis was conducted using Review Manager 5.4 and STATA 18.0 software.ResultsA total of 11 randomized controlled studies were included, with 6 countries and 696 participants participating. Our findings showed that UAWD was associated with a significant benefit in healing rate (OR = 2.60, 95% CI: [1.67, 4.03], P < 0.0001, I2 = 25%), wound healing time (MD = -11.94, 95% CI: [-23.65, -0.23], P = 0.05, I2 = 99%), percentage reduction in wound size (MD = 14.2, 95% CI: [10.8, 17.6], P = 0.47, I2 = 32%), effectiveness of treatment (OR = 10.3, 95% CI: [4.68, 22.66], P < 0.00001, I2 = 0%). Moreover, UAWD did not cause any significant adverse reactions. However, there was no obvious difference in wound blood perfusion (MD = 0.25, 95% CI: [-0.01, 0.52], P = 0.06, I2 = 90%), transcutaneous oxygen partial pressure (MD = 14.34, 95% CI: [-10.03, 38.71], P = 0.25, I2 = 98%).ConclusionUAWD can significantly improve wound healing rate, shorten wound healing time, accelerate wound area reduction, and improve clinical treatment effectiveness without significant adverse reactions. Although there is no significant difference in transcutaneous oxygen pressure and wound blood flow perfusion between UAWD and SWC. So we look forward to more scientifically blinded, placebo-controlled, high-quality studies in the future, to enable researchers to obtain more complete and accurate analytical data, in order to improve the scientific and credibility of the evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024501198

Study on energy dynamic change law in the process of water-contained coal caused by liquid nitrogen freezing

To study the energy dynamic change law of moisture-contained coal in the process of liquid nitrogen freezing, a self-developed acoustic emission (AE) experimental system for the whole process of liquid nitrogen frozen coal was utilized to analyze the characteristics and the change laws of AE energy dissipation in the whole process of liquid nitrogen freezing in coal with different moisture contents. The results shown that AE energy during liquid nitrogen freezing of coal was divided into steep, fluctuating and calm periods in the time domain. The primary and secondary peaks of energy were both positively linearly related to moisture content, and the primary and secondary energy peak of 5.96% moisture content were 1.66 and 2.26 times higher than those of dry coal. The cumulative energy of liquid nitrogen frozen coal, divided into three stages of steep increase, slow growth and stabilization versus time, was positively linearly related to moisture content, which of 5.96% moisture contained coal was 2.88 times higher than that of dry coal. The energy amplitude of different moisture content coals was mostly concentrated in the range of 40-50 dB, accounting for 94.39%-99.11% of the total, and decreased linearly with the increasing moisture content of coal. The time series of acoustic emission ringing counts in liquid nitrogen frozen coals had chaotic fractal characteristics, and the correlation dimensions of the steep increase, slow growth and stable stages were positively exponentially, linearly and linearly correlated with the moisture content, respectively. Furthermore, the correlation dimension in the steep increase stage of 5.96% moisture contained coal was 2.00 and 5.78 times higher than that of the slow growth and stable stage, respectively. The type of coal cracks produced by the liquid nitrogen freezing was mainly tensile, its proportion with the increasing moisture content was a negative exponential decrease, and the proportion of shear cracks positively linearly increased with the increasing moisture content. The increase of moisture in coal strengthened the freezing and expansion force generated by the water-ice phase transition during the liquid nitrogen freezing process, and the increase of energy dissipation contributed to the rapid development of pore-crack and the structural damage and plastic deformation of coal. However, the structural damage was difficult to detect in real time and can be inverted by AE energy

Simultaneous radical cystectomy and nephroureterectomy in the treatment of panurothelial carcinoma: a systematic review and single-arm meta-analysis

BackgroundPanurothelial carcinoma is a rare and aggressive malignancy that requires effective treatment strategies to enhance patient outcomes.MethodsWe conducted a systematic search of English publications in databases including PubMed, Embase, Cochrane Library, and Web of Science up to May 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Methodological Quality and Synthesis of Case Series and Case Reports tool. Data statistics and analysis were performed using Stata 15.1 software (StataSE, USA).ResultsSix studies involving 339 patients were included in the analysis. Meta-analysis revealed that Simultaneous Radical Cystectomy and Nephroureterectomy had 2-year and 5-year overall survival rates of 68% (95% CI 60%-76%, I2 = 12.4%, P < 0.001) and 44% (95% CI 36%-53%, I2 = 0, P < 0.001), respectively. The 2-year and 5-year progression-free survival rates were 91% (95% CI 86%-95%, I2 = 95%, P < 0.001) and 65% (95% CI 58%-73%, I2 = 91.5%, P < 0.001), respectively. The 2-year and 5-year cancer-specific survival rates were 73% (95% CI 66%-81%, I2 = 16.7%, P < 0.001) and 57% (95% CI 49%-66%, I2 = 0, P < 0.001), respectively. Additionally, the incidence of minor complications was 19% (95% CI 15%-23%, P < 0.01), major complications was 49% (95% CI 34%-63%, P < 0.01), and the intraoperative blood transfusion rate was 53% (95% CI 44%-61%, P < 0.01).ConclusionsSimultaneous radical cystectomy and nephroureterectomy represent feasible approaches for the treatment of Panurothelial carcinoma. Nonetheless, a comprehensive assessment of the surgical risks and benefits is imperative, and larger-scale prospective cohort studies are required to validate therapeutic efficacy. Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023426401

Natural product nanozymes of herbal extract galangin in managing hepatocellular carcinoma

Numerous local herbal extract species have been investigated as potential medicinal ingredients due to their promising anti-cancer properties. However, the primary constraint of the class of plant flavonoids lies in their low solubility and limited membrane permeability, leading to chemical instability and restricted bioavailability that impede biomedical applications. In this study, we have developed an ideal nanozyme-Galazyme, comprising galangin-loaded copper Nanozyme coated by DSPE-PEG, which amplifies oxidative stress to induce apoptosis via the regulation of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation. Galazyme exhibited significant peroxidase mimetic activity, demonstrating its potential to generate ROS and elevate oxidative stress. Upon uptake by HepG-2 cells, Galazyme efficiently converts excess hydrogen peroxide (H2O2) into highly reactive •OH radicals and upregulates MAPK expression, leading to the activation of Bax and Caspase 3, thereby promoting irreversible tumor cell apoptosis. Both in vitro and in vivo results demonstrate that Galazyme inhibits tumor cell growth and induces apoptosis by generating ample ROS and activating the MAPK pathway. Our study offers novel evidence supporting the enhancement of Galazyme-induced apoptosis through the upregulation of Bax and Caspase 3, along with the elucidation of the interaction between MAPK and apoptosis

Effects of Different Building Materials and Treatments on Sound Field Characteristics of the Concert Hall

The effects of different building materials on sound field characteristics of the concert hall were studied by experimental study and numerical simulations. A single non-directivity excitation sound source in situ test was carried out. The acoustic analysis model of the multifunctional concert hall was established. The reverberation time, the early decay time, the speech transmission index and the sound pressure level (SPL) were tested. The architectural treatment solutions with or without sound absorption in the design ceiling, sound absorption on the side walls, the influence of ceiling form on acoustic characteristics, and the acoustic characteristics of different positions on the first and second floors were analyzed, respectively. Simulation results show that there was little difference in reverberation time at different reception points by using the same treatment solutions, and the speech transmission index increased with the distance of the reception point. The language performance of the positions on the second was better than on the first floor. The SPL decreased with increasing distance from the receiving point. The ceiling form had no significant effects on the acoustic characteristics of the multifunctional concert hall, and the reverberation time was smaller when acoustic materials were used in the ceiling than the side walls. Meanwhile, the language transmission performance in multifunctional concert halls was improved. The difference between the maximum and minimum sound pressure levels for a sound-absorbing material ceiling is less than that of a non-sound-absorbing material

Study on the Influence of PCA Pre-Treatment on Pig Face Identification with Random Forest

To explore the application of a traditional machine learning model in the intelligent management of pigs, in this paper, the influence of PCA pre-treatment on pig face identification with RF is studied. By this testing method, the parameters of two testing schemes, one adopting RF alone and the other adopting RF + PCA, were determined to be 65 and 70, respectively. With individual identification tests carried out on 10 pigs, accuracy, recall, and f1-score were increased by 2.66, 2.76, and 2.81 percentage points, respectively. Except for the slight increase in training time, the test time was reduced to 75% of the old scheme, and the efficiency of the optimized scheme was greatly improved. It indicates that PCA pre-treatment positively improved the efficiency of individual pig identification with RF. Furthermore, it provides experimental support for the mobile terminals and the embedded application of RF classifiers

Efficacy and safety of minimally invasive percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of upper urinary tract stones (> 1 cm): a systematic review and meta-analysis of 18 randomized controlled trials

Abstract Background The advantages and disadvantages of retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (mPCNL) for treatment of upper urinary tract calculi have not been conclusively determined. Methods In this meta-analysis, We comprehensively evaluated the performance of the two surgical approaches in treatment of upper urinary calculi. We searched the Pubmed, Embase, Cochrane and Web of science databases for randomized controlled trial (RCT) articles on RIRS and mPCNL upto December 2022. Data were extracted by two independent reviewers and subjected to the meta-analysis using the Stata 15.1 software (StataSE, USA). Results A total of 18 eligible RCTs involving 1733 patients were included in this study. The meta-analysis revealed that mPCNL of 1–2 cm or 2–3 cm stones had a higher stone clearance rate (RR:1.08, 95%CI (1.03, 1.14), p = 0.002) and shorter operation time (WMD : -10.85 min, 95%CI (-16.76, -4.94), p<0.001). However, it was associated with more hospital stay time (WMD :1.01 day, 95%CI(0.53, 1.5), p<0.001), hemoglobin drops (WMD :0.27 g/dl, 95%CI (0.14, 0.41), p<0.001), blood transfusion rate (RR:5.04, 95%CI(1.62, 15.65), p = 0.005), pain visual analogue score (WMD:0.75, 95%CI (0.04, 1.46), p = 0.037), hospital costs (SMD :-0.97, 95%CI (-1.19, -0.76), p<0.001) and major complications (RR:1.89, 95%CI(1.01, 3.53), p = 0.045). Conclusion Therefore, in terms of surgical effects and operation time, mPCNL is superior to RIRS, but is inferior with regards to other perioperative parameters. These factors should be fully considered in clinical decision making

Accurate control of dual-receptor-engineered T cell activity through a bifunctional anti-angiogenic peptide

Abstract Background Chimeric antigen receptors (CARs) presented on T cell surfaces enable redirection of T cell specificity, which has enormous promise in antitumor therapy. However, excessive activity and poor control over such engineered T cells cause significant safety challenges, such as cytokine release syndrome and organ toxicities. To enhance the specificity and controllable activity of CAR-T cells, we report a novel switchable dual-receptor CAR-engineered T (sdCAR-T) cell and a new switch molecule of FITC-HM-3 bifunctional molecule (FHBM) in this study. Methods We designed a fusion molecule comprising FITC and HM-3. HM-3, an antitumor peptide including an Arg-Gly-Asp sequence, can specifically target integrin αvβ3 that is presented on some tumor cells. Moreover, to improve the specificity of CAR-T cells, we also generated the sdCAR-T cell line against cognate tumor cells expressing human mesothelin (MSLN) and integrin αvβ3. Finally, the activity of sdCAR-T cell and FHBM is verified via in vitro and in vivo experiments. Results In the presence of FHBM, the designed sdCAR-T cells exerted high activity including activation and proliferation and had specific cytotoxicity in a time- and dose-dependent manner in vitro. Furthermore, using a combination of FHBM in nude mice, sdCAR-T cells significantly inhibited the growth of MSLN+ K562 cells and released lower levels of the cytokines (e.g., interleukin-2, interferon γ, interleukin-6, and tumor necrosis factor α) relative to conventional CAR-T cells, obtaining specific, controllable, and enhanced cytotoxicity. Conclusions Our data indicate that FHBM can accurately control timing and dose of injected CAR-T cells, and sdCAR-T cells exert significant antitumor activity while releasing lower levels of cytokines for the cognate tumor cells expressing both MSLN and integrin αvβ3. Therefore, combination therapies using sdCAR-T cells and the switch molecule FHBM have significant potential to treat malignancies