Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study.

Backgroud: Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. Materials and methods: This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. Results: According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. Conclusions: In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

Methods for improving the properties of zinc for the application of biodegradable vascular stents.

Biodegradable stents can support vessels for an extended period, maintain vascular patency, and progressively degrade once vascular remodeling is completed, thereby reducing the constraints of traditional metal stents. An ideal degradable stent must have good mechanical properties, degradation behavior, and biocompatibility. Zinc has become a new type of biodegradable metal after magnesium and iron, owing to its suitable degradation rate and good biocompatibility. However, zinc's poor strength and ductility make it unsuitable as a vascular stent material. Therefore, this paper reviewed the primary methods for improving the overall properties of zinc. By discussing the mechanical properties, degradation behavior, and biocompatibility of various improvement strategies, we found that alloying is the most common, simple, and effective method to improve mechanical properties. Deformation processing can further improve the mechanical properties by changing the microstructures of zinc alloys. Surface modification is an important means to improve the biological activity, blood compatibility and corrosion resistance of zinc alloys. Meanwhile, structural design can not only improve the mechanical properties of the vascular stents, but also endow the stents with special properties such as negative Poisson 's ratio. Manufacturing zinc alloys with excellent degradation properties, improved mechanical properties and strong biocompatibility and exploring their mechanism of interaction with the human body remain areas for future research.

Recurrent laryngeal never monitoring versus non-monitoring in parathyroid surgery.

Background: Although intraoperative neural monitoring (IONM) is well established in thyroid surgery, it is less commonly analyzed in parathyroid operations. This study presents the results of IONM for primary and secondary hyperparathyroidism surgery. Methods: We retrospectively assessed 270 patients with primary hyperparathyroidism (PHPT), 53 patients with secondary hyperparathyroidism (SHPT), and 300 patients with thyroid cancer from June 2010 to June 2022 in one hospital in China. The follow-up was 12 months. Demographic, electromyography data from IONM, laboratory, and clinical information were collected. Laryngoscopy was collected from 109 patients with PHPT in whom IONM was not used. All groups were assessed by Pearson's chi-square test and Fisher's exact probability method to verify the relationship between parathyroid size and location, duration of surgery, preoperative concordant localization, laryngeal pain, IONM outcomes, cure rate, and RLN injury. Visual analog scale (VAS) assessed laryngeal pain. RLN outcomes were measured according to nerves at risk (NAR). Results: The study comprehended 918 NAR, that is 272, 105, 109, and 432 NAR for PHPT, SHPT with IONM, PHPT without IONM, and thyroid surgery control group, respectively. IONM successfully prevented RLN injury (P<0.001, P=0.012): Fifteen (5.51%) RLNs experienced altered nerve EMG profiles during surgery, and five (1.84%) experienced transient RLN injury in PHPT patients. Five (4.76%) RLNs were found to have altered EMG profiles during surgery, and one (0.95%) RLN had a transient RLN injury in SHPT patients. There was no permanent nerve injury (0.00%) in this series. There was no association between location, gland size, preoperative concordant localization, cure rate, duration of surgery, and IONM (P >0.05). Duration of surgery was associated with postoperative pharyngeal discomfort (P=0.026, P=0.024). Transient RLN injury was significantly lower in patients with PHPT who underwent IONM than in those who did not. Intraoperative neuromonitoring played an effective role in protecting the recurrent laryngeal nerve (P=0.035). Compared with parathyroidectomy, thyroidectomy had a higher rate of RLN injury (5.32%, P<0.001). Conclusion: IONM for SHPT and PHPT offers rapid anatomical gland identification and RLN functional results for effective RLN protection and reduced RLN damage rates.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices.

The Special Issue entitled "Biomechanical Study and Analysis for Cardiovascular/Skeletal Materials and Devices" addresses biological functional materials and devices relevant to cardiovascular diseases and orthopedic conditions [...].

Dynamic Response and Numerical Simulation of Closed-Cell Al Foams.

The drop hammer impact test was carried out to investigate the dynamic response of closed-cell Al foams. A relatively reasonable method was also developed to evaluate the velocity sensitivity of cellular material. The typical impact load-displacement curve exhibited two stages containing the initial compression stage and the progressive crushing stage. Three compressive damage behaviors and four failure modes of closed-cell Al foams were revealed, while the effect of velocity on the impact properties and the energy absorption capacity of different specimens were investigated. The results showed that the specific energy absorption of the specimens increased with the increasing density of the specimen and the impact velocity. However, the specimens with higher specific energy absorption seemed not to indicate better cushioning performance due to the shorter crushing displacement. In addition, the uniaxial impact simulation of two-dimensional (2D) Voronoi-based foam specimens was conducted at higher impact velocities. The simulation results of impact properties and deformation behavior agreed reasonably well with the experimental results, exhibiting similar velocity insensitivity of peak loads and deformation morphologies during uniaxial impact.

Edaravone protects against liver fibrosis progression via decreasing the IL-1ß secretion of macrophages.

Edaravone (EDA), a strong novel free radical scavenger, have been demonstrated to exert neurovascular protective effects clinically. Furthermore, EDA can suppress the lung injury, pulmonary fibrosis and skin fibrosis, while the precise effects and mechanisms of EDA on liver injury and fibrosis remain unclear. The effects of EDA on the Thioacetamide (TAA)-induced liver fibrosis were evaluated by sirius red staining, α-SMA immunohistochemistry. The percentages of immune cell subsets were analyzed by flow cytometry. Immunofluorescence assay was performed to identify the fibrotic properties of hepatic stellate cells (HSCs). Western blot and qPCR were used to detect the levels of liver fibrosis-related molecules and IL-1ß. EDA displayed a hepatic protective role in TAA-induced chronic liver fibrosis via inhibiting monocyte/macrophages recruitment and IL-1ß production of macrophages. Mechanically, EDA inhibited of NF-κB signal pathway and reactive oxygen species (ROS) production in macrophages. Moreover, EDA treatment indirectly suppressed the activation of HSCs by decreasing the IL-1ß secretion of macrophages. Together, EDA protects against TAA-induced liver fibrosis via decreasing the IL-1ß production of macrophages, thereby providing a feasible solution for clinical treatment of liver fibrosis.

Zinc-Based Biodegradable Materials for Orthopaedic Internal Fixation.

Traditional inert materials used in internal fixation have caused many complications and generally require removal with secondary surgeries. Biodegradable materials, such as magnesium (Mg)-, iron (Fe)- and zinc (Zn)-based alloys, open up a new pathway to address those issues. During the last decades, Mg-based alloys have attracted much attention by researchers. However, the issues with an over-fast degradation rate and release of hydrogen still need to be overcome. Zn alloys have comparable mechanical properties with traditional metal materials, e.g., titanium (Ti), and have a moderate degradation rate, potentially serving as a good candidate for internal fixation materials, especially at load-bearing sites of the skeleton. Emerging Zn-based alloys and composites have been developed in recent years and in vitro and in vivo studies have been performed to explore their biodegradability, mechanical property, and biocompatibility in order to move towards the ultimate goal of clinical application in fracture fixation. This article seeks to offer a review of related research progress on Zn-based biodegradable materials, which may provide a useful reference for future studies on Zn-based biodegradable materials targeting applications in orthopedic internal fixation.

Compressive Properties and Degradable Behavior of Biodegradable Porous Zinc Fabricated with the Protein Foaming Method.

A new protein foaming-consolidation method for preparing porous zinc was developed using three proteins (egg white protein (EWP), bovine bone collagen protein (BBCP), and fish bone collagen protein (FBCP)) as both consolidating and foaming agents. The preparation route utilized powder mixing and sintering processing, which could be divided into three steps: slurry preparation, low-temperature foaming, and high-temperature sintering. The morphological characteristics of the pore structures revealed that the porous zinc had an interconnected open-cell structure. Compared to the porous zinc prepared with EWP or BBCP, the porous zinc prepared with FBCP possessed the largest average pore size and the highest compressive properties. The porosity of the porous zinc increased with the stirring time, the content of protein and sucrose, and higher sintering temperatures. Moreover, a compression test and immersion test were performed to investigate the stress-strain behavior and corrosion properties of the resulting porous zinc. A fluctuated stress plateau could be found due to the brittle fracture of the porous cells. The porous zinc prepared with FBCP showed the highest compressive strength and elastic modulus. The corrosion rate of the porous zinc obtained through an immersion test in vitro using simulated bodily fluids on the thirty-second day was close to 0.02 mm/year. The corresponding corrosion mechanism of porous zinc was also discussed.

Finite element analysis of the mechanical performance of a zinc alloy stent with the tenon-and-mortise structure.

BACKGROUND: Inadequate scaffolding performance hinders the clinical application of the biodegradable zinc alloy stents. OBJECTIVE: In this study we propose a novel stent with the tenon-and-mortise structure to improve its scaffolding performance. METHODS: 3D models of stents were established in Pro/E. Based on the biodegradable zinc alloy material and two numerical simulation experiments were performed in ABAQUS. Firstly, the novel stent could be compressed to a small-closed ring by a crimp shell and can form a tenon-and-mortise structure after expanded by a balloon. Finally, 0.35 MPa was applied to the crimp shell to test the scaffolding performance of the novel stent and meanwhile compare it with an ordinary stent. RESULTS: Results showed that the novel stent decreased the recoiling ratio by 70.7% compared with the ordinary stent, indicating the novel structure improved the scaffolding performance of the biodegradable zinc alloy stent. CONCLUSION: This study proposes a novel design that is expected to improve the scaffolding performance of biodegradable stents.

Compressive Behavior of Al-TiB2 Composite Foams Fabricated under Increased Pressure.

The application of increased pressure was used as a strategy to investigate the effect of different cell structures on the mechanical properties of Al-TiB2 composite foams. In situ Al-xTiB2 (x = 5, 10 wt.%) composites were foamed under three different pressures (0.1 MPa, 0.24 MPa, 0.4 MPa) through the liquid melt route. The macro-structure of the composite foams was analyzed in terms of cell size distribution measured by X-ray microcomputed tomography (micro-CT). It was found that the mean cell size decreases, and the cell size distribution range narrows with increasing pressure. Uniaxial compression tests revealed that the stress fluctuation (Rsd) of 10TiB2 foams is larger than that of 5TiB2 foams under the same pressure. Moreover, cell size refinement causes the simultaneous deformation of multi-layer cells, which leads to an enhancement in the energy absorption efficiency and specific energy absorption. The comparison of experimental data with theoretical predictions (G&A model) is discussed.

Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.

BACKGROUND: Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. AIM: To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). METHODS: C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. RESULTS: First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-ß1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-ß1. CONCLUSION: Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.

Mechanical analysis of a novel biodegradable zinc alloy stent based on a degradation model.

BACKGROUND: Biodegradable stents display insufficient scaffold performance due to their poor Young's Modulus. In addition, the corresponding biodegradable materials harbor weakened structures during degradation processes. Consequently, such stents have not been extensively applied in clinical therapy. In this study, the scaffold performance of a patented stent and its ability to reshape damaged vessels during degradation process were evaluated. METHODS: A common stent was chosen as a control to assess the mechanical behavior of the patented stent. Finite element analysis was used to simulate stent deployment into a 40% stenotic vessel. A material corrosion model involving uniform and stress corrosion was implemented within the finite element framework to update the stress state following degradation. RESULTS: The results showed that radial recoiling ratio and mass loss ratio of the patented stent is 7.19% and 3.1%, respectively, which are definitely lower than those of the common stent with the corresponding values of 22.6% and 14.1%, respectively. Moreover, the patented stent displayed stronger scaffold performance in a corrosive environment and the plaque treated with patented stents had a larger and flatter lumen. CONCLUSION: Owing to its improved mechanical performance, the novel biodegradable zinc alloy stent reported here has high potential as an alternative choice in surgery.