A functional study of zinc-titanium coatings and exploration of the intrinsic correlation between angiogenesis and osteogenesis.

With the development of implant applications, osseointegration has become a criterion for implant success. A good blood supply is essential for successful osseointegration. To improve the pro-angiogenic ability of the implants, in this experiment we introduced zinc into the titanium coating. The physical morphology, biocompatibility, pro-angiogenic ability, and osteogenic effect of the zinc-containing titanium coatings were investigated. The pro-angiogenic effect of zinc ions was determined, and the intrinsic link between angiogenesis and osteogenesis under the effect of zinc ions was investigated. Zinc-containing titanium coating was prepared using a micro-arc oxidation (MAO) technique. The physical properties of the coating materials were determined by analyzing the microstructure, roughness, hydrophilic properties, constituent elements, and ionic release of the coating. The biocompatibility of the coating materials was examined using apoptosis and proliferation assays of human umbilical vein endothelial cells (HUVECs). The pro-angiogenic function and osteogenic ability of the zinc-containing coating were investigated by CD31 immunofluorescence staining and quantitative polymerase chain reaction (q-PCR) assay. The optimal concentration of zinc ions for pro-angiogenesis was screened by ion assay. Conditioned media (CM) were prepared for the experiments. The intrinsic link between angiogenesis and osteogenesis was determined by q-PCR to detect the expression of genes related to HUVECs and BMSCs after culture in CM. The prepared Zn-containing micro-arc oxide coatings were shown to have good physical properties, stable Zn2+ release ability, and biocompatibility, as well as good angiogenic and osteogenic potential. In addition, ion experiments confirmed that 60 µM Zn2+ exhibited the best angiogenic effect; more importantly, a mutual promotion between angiogenesis and osteogenesis regeneration in the Zn2+ microenvironment was also found. The introduction of Zn2+ improved the implants' functionality and laid the foundation for the clinical application of Zn2+ pro-angiogenesis.

Effects of acute normovolemic hemodilution on allogeneic blood transfusion & coagulation in orthognathic surgery: A randomized study.

BACKGROUND: Acute normovolemic hemodilution (ANH) is one of the important techniques predominantly used in cardiac, hepatic, and vascular surgery for decreasing allogeneic blood transfusion. However, the effect of ANH in orthognathic surgery has been rarely studied. Therefore, this study aims to assess the ANH-mediated reduction in the allogeneic red blood cell transfusion for orthognathic surgery patients. STUDY DESIGN AND METHODS: In this single-center study, 18-80 years old patients were recruited. Patients with hemoglobin ≥11 g/dL and normal coagulation function were randomly divided into ANH or standard treatment group. RESULTS: Ninety six patients underwent ANH, and 101 patients received standard treatment. No differences in demographic or major pre-operative characteristics were observed between the two groups. One patient in the ANH and three patients in the standard treatment group received allogeneic blood [3(2.97%) vs. 1(1.16%), control vs. ANH, p = .395]. Multivariate logistic regression analysis revealed that ANH treatment was not associated with transfusion of allogeneic blood (p = .763). After retransfusing autologous blood, PT and APTT in the ANH group significantly increased compared to standard treatment group (PT: -1.73 ± 1.09 vs. -2.15 ± 1.06, p = .035; APTT: -6.39 ± 5.76 vs. -8.16 ± 5.70, p = .031; control vs. ANH). No significant differences between the two groups were observed for changes in coagulation parameters at first postoperative day. However, platelet counts in the ANH group decreased compared to the standard group. No significant difference in major adverse outcomes was observed between the two groups. CONCLUSION: ANH did not reduce the incidence of allogeneic transfusion in patients undergoing orthognathic surgery.

Association of urinary bisphenol A with chronic obstructive pulmonary disease-related diseases: evidence from the National Health and Nutrition Examination Survey database (2005-2016).

In vivo and in vitro studies have found that exposure to bisphenol A (BPA) can lead to pulmonary diseases, but there exists little evidence regarding the association between urinary BPA level and chronic obstructive pulmonary disease (COPD)-related diseases in the population. National Health and Nutrition Examination Survey data, from 2005 to 2016, were utilized in this study. Participants who self-reported having emphysema, chronic bronchitis, or COPD were defined as having COPD-related diseases. A multivariate logistic regression analysis was used to analyze the association of urinary BPA with COPD-related diseases in the overall population and according to sex. Three separate models including different covariates were used in our analyses. The association of urinary BPA with COPD-related diseases in different subgroups (age, smoking status, participants belonging to "ever had asthma" and "ever had cardiovascular disease") other than sex was also analyzed. Based on the different models, 9189, 7006, and 6946 participants were used in our study. BPA was found to be significantly associated with COPD-related diseases in all models. The concentration of BPA in urine was significantly associated with COPD-related diseases regardless of whether BPA concentration was treated as a continuous variable (odds ratio (OR): 1.24, 95% confidence interval (CI): 1.11-1.38, in model 3) or as tertiles (OR: 2.01, 95% CI: 1.49-2.72, between the lowest group and highest group, in model 3). This association was significant among male but not female participants. BPA also demonstrated a significant association with emphysema and chronic bronchitis in adults, particularly in males. No significant interaction was found for all the other subgroup analyses. Urinary BPA was associated with COPD-related diseases in adult participants, especially males.

Remimazolam induced cognitive dysfunction in mice via glutamate excitotoxicity.

Objective: Several lines of evidence demonstrated the role of anesthetic drugs in cognitive functions. Some anesthetic agents have been confirmed to be associated with long-term spatial memory and learning in aged animal models. Methods: C57BL/6 mice were divided into four different groups based on different concentrations of remimazolam treatments. Behavioral phenotype was observed by open field, rota rod, Morris water maze, and elevated plus maze test. Western blot was performed to see the expression pattern of different proteins. Confocal microscopy images were taken for neuronal and glial cells to see the effect of remimazolam on CNS cells. Results: We showed that remimazolam, a new anesthetic drug, impaired cognitive behavior. Repetitive doses of remimazolam have been found to induce neuronal loss with a significant change in morphology. Here, we showed that a higher concentration of remimazolam had a significant effect on CNS cell activation. We showed that remimazolam caused memory dysfunction by inducing neuronal apoptosis via glutamate excitotoxicity. It also exhibited amyloid ß plaque in the brain via abnormal phosphorylation of tau protein. Remimazolam-mediated regulation of glial cells in mouse cortex was observed and robust activation of astrocytes and microglial cells was found. Finally, we assessed the behavioral phenotype of mice and found that treatment with remimazolam induced significant behavioral changes and memory dysfunction. Conclusions: This study provides insight into the mechanism of anesthetic drug-induced memory deficits and may help improve the therapeutic effects of anesthesia agents in clinical applications.

Clinical Validation of the Impact of Branch Stent Extension on Hemodynamics in ISF-TEVAR Involving LSA Reconstruction.

Background: The study of hemodynamics regarding thoracic endovascular aortic repair (TEVAR) is helpful to improve the surgical efficacy. Objective: Correlations between hemodynamic changes and branch stent extension length and interference factors for branch stent extension length of in situ fenestration TEVAR (ISF-TEVAR) involving the left subclavian artery (LSA) were evaluated. Materials and Methods: This study retrospectively analyzed 196 patients with Stanford type B aortic dissection who received in situ laser fenestrated thoracic endovascular aortic repair with LSA fenestration from April 2014 to March 2021. Branch stent extension to the main stent graft was evaluated by the computed tomographic angiography (CTA). Hemodynamic change of LSA was defined as a 20 mmHg interbrachial systolic pressure difference. The factors affecting the extension of the branch stent were also evaluated. Results: All patients underwent ISF-TEVAR with LSA fenestration, and there was no recurrence during the follow-up. The mean length of the branch stent extension was 10.37 ± 0.34 mm, which was used to divide the patients into long and short groups. Asymptomatic hemodynamic changes (defined as a 20 mmHg interbrachial systolic pressure difference) in LSA were observed in 61 patients undergoing ISF-TEVAR involving LSA fenestration. The Spearman correlation analysis showed extension length of a branch stent >1.5 cm elevated the risk of hemodynamic changes. Conclusion: Overall, we conclude that branch stent extension length >1.5 cm induced LSA hemodynamic changes. Appropriate shortening of the stent extension length can improve the curative effect of ISF-TEVAR, especially when faced with a type II/III aortic arch and stent angles of <30 degrees.

Comparison of multiple imaging modalities for measuring orifice diameter and selecting occluder size in patients undergoing left atrial appendage closure.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) can safely and effectively prevent stroke events caused by atrial fibrillation. However, the structure of the LAA is highly variable among individuals, and the optimal method for obtaining measurements remains unknown. HYPOTHESIS: We aimed to study the accuracy of left atrial computed tomography angiography (CTA), three-dimensional (3D) reconstruction using CTA, two-dimensional transesophageal echocardiography (2D-TEE), and digital subtraction angiography (DSA) for measuring the diameter of the LAA and compare their value for selecting occluder size. METHODS: We retrospectively evaluated data for 148 patients with nonvalvular atrial fibrillation who underwent successful LAAC. CTA and 2D-TEE of the left atrium and pulmonary vein were performed before LAAC. We performed 3D reconstruction of the left atrium and LAA using Mimics and 3-matics software. DSA of the LAA was performed during surgery. RESULTS: Values measured via CTA 3D reconstruction were significantly higher than those measured using other methods. DSA-measured values were significantly lower than those measured via CTA and CTA 3D reconstruction. Occluder size was positively correlated with LAA orifice diameter. The differences between occluder size and DSA, 2D-TEE, CTA, CTA 3D reconstruction measurements were 4.96 ± 2.58, 4.64 ± 2.50, 4.04 ± 1.37, and 2.92 ± 1.38 mm, respectively. Intraclass correlation coefficients for these methods were -.067, .006, .241, and .519, respectively. CONCLUSION: CTA 3D reconstruction provides the best correlation and consistency between the measured LAA orifice diameter and occluder size. Adding 2-4 mm to the maximum LAA orifice diameter based on 3D-CTA may aid in selecting the appropriate WATCHMAN device.

Nrf2 attenuates ferroptosis-mediated IIR-ALI by modulating TERT and SLC7A11.

Acute lung injury (ALI) carries a mortality rate of ~50% and is a hot topic in the world of critical illness research. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical modulator of intracellular oxidative homeostasis and serves as an antioxidant. The Nrf2-related anti-oxidative stress is strongly associated with ferroptosis suppression. Meanwhile, telomerase reverse transcriptase (TERT), the catalytic portion of the telomerase protein, is reported to travel to the mitochondria to alleviate ROS. In our study, we found that TERT was significantly reduced in lung tissue of Nrf2-/- mice in the model of intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI). In addition, MDA levels showed marked increase, whereas GSH and GPX4 levels fell drastically in ALI models. Moreover, typical-related structural changes were observed in the type II alveolar epithelial cells in the IIR model. We further employed the scanning transmission X-ray microscopy (STXM) to examine Fe levels and distribution within cells. Based on our observations, massive aggregates of Fe were found in the MLE-12 cells upon OGD/R (oxygen and glucose deprivation/reperfusion) induction. Additionally, Nrf2 silencing dramatically reduced TERT and SLC7A11 levels, and further exacerbated cellular injuries. In contrast, TERT-overexpressing cells exhibited marked elevation in SLC7A11 levels and thereby inhibited ferroptosis. Collectively, these data suggest that Nrf2 can negatively regulate ferroptosis via modulation of TERT and SLC7A11 levels. The conclusion from this study brings insight into new candidates that can be targeted in future IIR-ALI therapy.

Effect of Hemodilution In Vitro with Hydroxyethyl Starch on Hemostasis.

BACKGROUND Hydroxyethyl starch (HES) solutions are used for volume expansion during surgery. We aimed to investigate how 6%HES 130/0.4 affects hemostasis. MATERIAL AND METHODS Blood samples were collected from 12 healthy adult volunteers, diluting with 6%HES 130/0.4 (HES group) or Ringer lactate solution (RL control group). The hemodilution ratio (HR) of citrated blood volume to plasma substitute volume was 10: 0 (undiluted), 10: 2, 10: 4, and 10: 6. Clotting factors activity was measured. Thrombin generation was monitored. Platelet function was analyzed. RESULTS 1) Activity of coagulation factor was decreased with increasing HR compared to undiluted baseline, and the activity of FVIII was significantly decreased in HES vs. RL. 2) Calibrated automated thrombography (CAT) results showed HES extended lag time, time to peak (ttpeak), start tail, and decreased peak of thrombin generation. Although lag time and ttpeak were significantly prolonged in HES vs. RL, endogenous thrombin potential (ETP) did not change. 3) Flow cytometric (FCM) analysis showed that HES reduced platelet phospholipids serine (PS) vs. baseline and RL. 4) HES significantly decreased antithrombin activity (AT: A) of the anticoagulant system with increasing HR vs. baseline and RL. 5) For fibrinolytic system, HES did not affect fibrinogen degradation products (FDP) and D-dimers (D-D) vs. baseline, or α2-antiplasmin (α2-AP) vs. RL. CONCLUSIONS By reducing FVIII activity and platelet PS expression, HES interfered with PS combining to FXIa, FVIIIa, and FVa, which affected the acceleration and explosion stage of thrombin. The decreased velocity and peak of thrombin generation delays and reduces clot formation. Combined 6%HES 130/0.4 decreased anticoagulant activity and may have clinical utility.

Regional anesthesia and lipid resuscitation for local anesthetic systemic toxicity in China: results of a survey by the orthopedic anesthesia group of the Chinese Society Of Anesthesiology.

BACKGROUND: Intravenous lipid emulsions have been introduced for the management of patients with Local Anesthetic Systemic Toxicity (LAST). These emulsions have been stated as a first-line treatment in the guidelines of several international anesthesia organizations. Nevertheless, the adoption of lipid rescue therapy by Chinese practitioners remains unknown. We, therefore, evaluated the current approaches to treat LAST and the use of lipid rescue therapy among anesthesiologists in China. METHODS: In September 2013, a 23-question survey on regional anesthesia practice and availability of lipid emulsions was sent by e-mail to directors or designated individuals at 41 academic anesthesiology departments listed by the orthopedic anesthesia group of the Chinese Society of Anesthesiology. RESULTS: Responses were received from 36 of the 41 (88 %) anesthesiology departments. To simplify the analysis, responses were divided into two groups according to the annual percentage of patients who received regional anesthesia (RA) for orthopedic anesthesia: 14 departments (39%) with high-utilization (≥ 50%) and 22 departments (61%) low-utilization (<50%) of RA. Ropivacaine and bupivacaine were the common drugs used for RA, which were independent of RA utilization. Interestingly, ultrasound-guided techniques were much more frequently used in low-utilization institutions than in high-utilization institutions (P = 0.025). Lipid emulsion was readily available in 8 of the 36 (22%) responding institutions, with 7 of the other 28 (25%) institutions planning to stock lipid emulsion. No differences in lipid availability and storage plans were observed between high- and low-utilization institutions. Lipid resuscitation was performed in five of the eight departments that had lipid emulsion. Eleven patients were successfully resuscitated and one was not. CONCLUSION: Lipid emulsion is not widely available in China to treat LAST resulted from RA for orthopedic patients. Efforts are required to promote lipid rescue therapy nationwide. TRIAL REGISTRATION: Chinese Clinical Trail Registry (Registration number # ChiCTR-EOR-15006960; Date of Retrospective Registration on August 23rd, 2015) http://www.chictr.org.cn/showproj.aspx?proj=11703 .

Effects of acute hypervolemic fluid infusion of hydroxyethyl starch and gelatin on hemostasis and possible mechanisms.

OBJECTIVE: The purpose of this study was to investigate the effects of acute hypervolemic fluid infusion (AHFI) of 6% hydroxyethyl starch (HES) 130/0.4 or 4% succinylated gelatin (GEL) on hemostasis and the possible mechanisms. METHODS: Thirty-six gastric cancer patients were randomized to receive AHFI of either HES, GEL or lactated Ringer's (RL) solution at the rate of 30 mL x kg(-1) x h( -1) from 20 minutes before to 40 minutes after induction of general anesthesia. RESULTS: Group HES and GEL had significantly prolonged PT and aPTT, decreased VIII:C and vWF immediately after AHFI. Statistically prolonged reaction time and coagulation time, and decreased growth angle were seen immediately after HES infusion. Maximum amplitude decreased significantly in group HES and GEL immediately after and 4 hours after AHFI. CONCLUSION: Gelatin reduced clot quality associated with derangements of fibrin polymerization and HES 130/0.4 delayed initiation of sufficient thrombin generation to convert fibrinogen to fibrin and impaired platelet function.

Effects of artificial colloids on haemostasis.

Artificial colloids are used in situations with a high risk of bleeding such as trauma or during surgery. Although more efficacious than crystalloids, colloids can be associated with derangements of the haemostatic system and may also interfere with normal haemostasis via a number of different mechanisms.