Co-Crystallization between Aliphatic Polyesters through Co-Inclusion Complexation with Small Molecule.

Crystalline/crystalline blends of polymer have shown advantages in the preparation of new polymeric materials. However, the regulation of co-crystallization in a blend is still full of challenges due to the preferential self-crystallization driven by thermodynamics. Here, an inclusion complex approach is proposed to facilitate the co-crystallization between crystalline polymers, because the crystallization process displays a prominent kinetics advantage when polymer chains are released from the inclusion complex. Poly(butylene succinate) (PBS), poly(butylene adipate) (PBA) and urea are chosen to form co-inclusion complexes, where PBS and PBA chains play as isolated guest molecules and urea molecules construct the host channel framework. The coalesced PBS/PBA blends are obtained by fast removing the urea framework and systematically investigated by differential scanning calorimetry, X-ray diffraction, proton nuclear magnetic resonance and Fourier transformation infrared spectrometry. It is demonstrated that PBA chains are co-crystallized into PBS extended-chain crystals in the coalesced blends, while such a phenomenon has not been detected in simply co-solution-blended samples. Though PBA chains could not be totally accommodated in the PBS extended-chain crystals, their co-crystallized content increases with the initial feeding ratio of PBA. Consequently, the melting point of the PBS extended-chain crystal gradually declines from 134.3 °C to 124.2 °C with an increasing PBA content. The PBA chains playing as defects mainly induce lattice expansion along the a-axis. In addition, when the co-crystals are soaked in tetrahydrofuran, some of the PBA chains are extracted out, leading to damage to the correlative PBS extended-chain crystals. This study shows that co-inclusion complexation with small molecules could be an effective way to promote co-crystallization behavior in polymer blends.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children.

BACKGROUND: Children undergoing strabismus surgery under sevoflurane anesthesia often experience emergence agitation (EA) and postoperative vomiting (POV). This study compared the effects of intraoperative dexmedetomidine, ketamine, and placebo on postoperative EA and POV. METHODS: Eighty-four children (aged two to seven years) undergoing elective strabismus surgery under sevoflurane anesthesia were randomly assigned to one of three groups (n = 28 each). Intraoperatively, the placebo, dexmedetomidine, and ketamine groups received normal saline, dexmedetomidine 1 µg·kg(-1) iv plus a 1 µg·kg(-1)·hr(-1) infusion, and ketamine 1 mg·kg(-1) iv plus a 1 mg·kg(-1)·hr(-1) infusion, respectively. Agitation scores (Pediatric Anesthesia Emergence Delirium [PAED] scale) and POV were assessed in the postanesthetic care unit (PACU) and for 24 hr on the ward. Pain scores and times to laryngeal mask airway (LMA™) removal, resumption of mental orientation, and discharge from the PACU were also assessed. RESULTS: Seventy-eight children completed the study. Peak PAED scores for EA were lower in the dexmedetomidine (P < 0.001) and ketamine (P = 0.002) groups than in the placebo group. Incidence of POV was lower in the dexmedetomidine group (15%) than in the ketamine (44%; P = 0.02) or placebo (45.8%; P = 0.02) groups. Pain scores on the ward were lower in the dexmedetomidine (P < 0.001) and ketamine (P < 0.001) groups than in the placebo group. Time to LMA removal was similar in all groups. Time for resumption of mental orientation and time to discharge from PACU were longer in the dexmedetomidine and ketamine groups than in the placebo group. CONCLUSIONS: Dexmedetomidine and ketamine appear to prevent postoperative agitation and pain after sevoflurane anesthesia for pediatric strabismus surgery. Dexmedetomidine also prevents POV.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

Purpose: To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC). Methods: This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images. A larger number of radiomic features were automatically extracted. Finally, a nomogram was built, incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were performed to validate the capability of the nomogram on both the training and validation sets. The nomogram models were compared with conventional US models. The DeLong test was adopted to compare different ROC curves. Results: The area under the receiver operating characteristic curve (AUC) of the radiologist was 0.67 [95% confidence interval (CI), 0.580-0.757] in the training cohort and 0.62 (95% CI, 0.467-0.746) in the validation cohort. Sixteen features from 3D US images were used to build the radiomics signature. The radiomics nomogram, which incorporated the radiomics signature, tumor location, and tumor size showed good calibration and discrimination in the training cohort (AUC, 0.810; 95% CI, 0.727-0.876) and the validation cohort (AUC, 0.798; 95% CI, 0.662-0.897). The result suggested that the diagnostic efficiency of the 3D US-based radiomics nomogram was better than that of the radiologist and it had a favorable discriminate performance with a higher AUC (DeLong test: p < 0.05). Conclusions: The 3D US-based radiomics signature nomogram, a noninvasive preoperative prediction method that incorporates tumor location and tumor size, presented more advantages over radiologist-reported ETE statuses for PTC.

Aesthetic outcome of intralesional injection of lauromacrogol as a single-agent treatment for uncomplicated infantile hemangiomas: A long-term follow-up study.

Infantile hemangiomas (IH) are at risk of incomplete regression with remnant permanent sequelae, ranging from passive waiting for spontaneous regression to active systemic administration. The application of traditional therapy involving injection of a sclerosing agent is limited due to the difficulty in achieving cosmetic improvement. This study aimed to explore a new injection method that could not only promote tumor regression but also achieve cosmetic improvement. A total of 122 IH (from 109 children) injected intralesionally with lauromacrogol in the Plastic Surgery Department of Fujian Medical University Union Hospital between 1 January 2012 and 1 June 2019 were enrolled in this study. The mean follow-up time was 2.9 years. Of 122 lesions studied, 111 (91.0%) achieved complete regression, 10 (8.2%) achieved significant regression and one (0.8%) achieved moderate regression. In terms of aesthetic appearance, 70 (57.4%) IH had no sequelae and the A score was 5/5. Twenty-one (17.2%) IH had minimal hyperpigmentation, hypopigmentation or telangiectasia and the A score was 4/5. Thirty-one (25.4%) IH had left mild or relatively obvious sequelae and the A score was 1-3/5. None of the 122 IH involved had rebound growth after terminating the treatment. Hyper- or hypopigmentation gradually faded over time and part of the IH had already returned to normal appearance by the time of long-term follow up. The results indicated that this new type of injection therapy significantly promoted the regression of uncomplicated IH and helped achieve the expected cosmetic appearance.

[Effect of aerobic exercise on the expression of CLK2 protein in liver of mice fed with high fat diet].

OBJECTIVE: To investigate the effects of aerobic exercise on Cdc2-like kinase (CLK2) protein expression and the fat content in liver of mice fed with high fat diet. METHODS: C57BL/6 mice were distributed in normal diet, high fat diet (fed with highfat diet during 16 weeks) and trained high fat diet group (fed with high-fat diet during 16 weeks and exercised during 8 weeks),10 mice in each group. The expression of CLK2 protein in liver of each group was detected by Western blot. The fat content of liver in each group was detected by oil red O staining, and the relative genes of fat metabolism in each group were evaluated by real-time quantitative PCR. RESULTS: The mice fed with high fat diet showed insulin resistance, the hepatic CLK2 content and fat content were increased compared to the normal diet group. Otherwise, the chronic physical exercise improved insulin resistance state, prevented the increasing of CLK2 in the liver and attenuated hepatic fat accumulation. CONCLUSION: Aerobic exercise could reduce the expression of CLK2 protein in the liver of mice fed with high fat diet.

Novel Calcium Phosphate Cement with Metformin-Loaded Chitosan for Odontogenic Differentiation of Human Dental Pulp Cells.

Metformin is an old and widely accepted first-line drug for treating type 2 diabetes. Our previous studies demonstrate that metformin can stimulate the osteo/odontogenic differentiation of human-induced pluripotent stem cell-derived mesenchymal stem cells and human dental pulp cells (DPCs). Due to the rapid dilution of metformin from the defect area, the aim of this study was to develop a drug delivery system with controlled release of metformin to promote cell viability and odontogenic differentiation of DPCs favoring dentin regeneration. Calcium phosphate cement (CPC) containing chitosan and metformin as a scaffold was synthesized. DPCs were seeded onto the scaffold, and the viability and proliferation were evaluated at several time points. For osteogenic differentiation analysis, alkaline phosphatase (ALP) activity was tested, cells were stained with Alizarin Red, and the expression of odontogenic markers was evaluated by real-time polymerase chain reaction. DPCs remained viable and attached well to the CPC-chitosan composite scaffold. Moreover, the addition of metformin to the CPC-chitosan composite did not adversely affect cell proliferation, compared to that of CPC control. Our data further revealed that the novel CPC-chitosan-metformin composite enhanced the odontogenic differentiation of DPCs, as evidenced by higher ALP activity, elevated expression of odontoblastic markers, and strong mineral deposition. These results suggest that the new CPC-chitosan-metformin composite is a highly promising scaffold with the potential for tissue engineering applications including dentin regeneration.