Mesenchymal stem cells in fibrotic diseases-the two sides of the same coin.

Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.

Prognostic factors and its predictive value in patients with metastatic spinal cancer.

BACKGROUND: The spine is the most common location of metastatic diseases. Treating a metastatic spinal tumor depends on many factors, including patients' overall health and life expectancy. The present study was conducted to investigate prognostic factors and clinical outcomes in patients with vertebral metastases. AIM: To investigate prognostic factors and their predictive value in patients with metastatic spinal cancer. METHODS: A retrospective analysis of 109 patients with metastatic spinal cancer was conducted between January 2015 and September 2017. The prognoses and survival were analyzed, and the effects of factors such as clinical features, treatment methods, primary lesions and affected spinal segments on the prognosis of patients with metastatic spinal cancer were discussed. The prognostic value of Frankel spinal cord injury functional classification scale, metastatic spinal cord compression (MSCC), spinal instability neoplastic score (SINS) and the revised Tokuhashi score for prediction of prognosis was explored in patients with metastatic spinal tumors. RESULTS: Age, comorbidity of metastasis from elsewhere, treatment methods, the number of spinal tumors, patient's attitude toward tumors and Karnofsky performance scale score have an effect on the prognosis of patients (all P < 0.05). With respect to classification of spinal cord injury, before operation, the proportion of grade B and grade C was higher in the group of patients who died than in the group of patients who survived, and that of grade D and grade E was lower in the group of patients who died than in the group of patients who survived (all P < 0.05). At 1 mo after operation, the proportion of grade A, B and C was higher in the group of patients who died than in the group of patients who survived, and that of grade E was lower in patients in the group of patients who died than in the group of patients who survived (all P < 0.05). MSCC occurred in four (14.3%) patients in the survival group and 17 (21.0%) patients in the death group (P < 0.05). All patients suffered from intractable pain, dysfunction in spinal cord and even paralysis. The proportion of SINS score of 1 to 6 points was lower in the death group than in the survival group, and the proportion of SINS score of 7 to 12 points was higher in the death group than in the survival group (all P < 0.05). The proportion of revised Tokuhashi score of 0 to 8 points and 9 to 11 points were higher in the death group than in the survival group, and the proportion of revised Tokuhashi score of 12 to 15 points was lower in the death group than in the survival group (all P < 0.05). Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were important factors influencing the surgical treatment of patients with metastatic spinal cancer (all P < 0.05). CONCLUSION: Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were helpful in predicting the prognosis of patients with metastatic spinal cancer.

Características posoperatorias de la faringoplastia combinada con amigdalectomía en comparación con la amigdalectomía en niños con síndrome obstructivo de apnea del sueño / Postoperative characteristics of combined pharyngoplasty and tonsillectomy versus tonsillectomy in children with obstructive sleep apnea syndrome

Objetivo. Identificar las ventajas posoperatorias de la amigdalectomía en conjunto con la faringoplastia en comparación con la amigdalectomía sola en niños con apnea obstructiva del sueño. Métodos. En un estudio prospectivo observacional, los pacientes que cumplían con los criterios del estudio fueron asignados aleatoriamente a dos grupos: el grupo de amigdalectomía y faringoplastia, y el grupo de solo amigdalectomía. En ambos grupos, también se practicó adenoidectomía a los pacientes con vegetaciones. Se compararon los procesos de cicatrización en la herida faríngea y las proporciones hemorrágicas. Además, se evaluó la función velofaríngea posoperatoria. Resultados. La faringoplastia junto con la amigdalectomía se practicó en 328 niños con apnea obstructiva del sueño debido a hipertrofia amigdalina, y la amigdalectomía sola, en 275 niños. Estas cohortes no mostraban diferencias demográficas significativas. Por otro lado, se encontró que la pérdida de sangre fue significativamente menor en el grupo que recibió amigdalectomía y faringoplastia (p < 0,01), y el proceso de cicatrización fue notablemente más breve. La función velofaríngea posoperatoria no resultó afectada. Conclusiones. En comparación con la amigdalectomía, la amigdalectomía junto con la faringoplastia redujeron la duración del proceso de cicatrización y la pérdida de sangre; no obstante, las complicaciones posoperatorias no aumentaron. En nuestra opinión, la combinación de faringoplastia y amigdalectomía reúne un gran potencial en el tratamiento de los niños con apnea obstructiva del sueño.

Purpose. The study aims to identify the postoperative advantages of tonsillectomy in conjunction with pharyngoplasty and tonsillectomy alone in children with obstructive sleep apneas. Methods. In a prospective observational study, patients who met the study criteria were randomly divided into two groups: tonsillectomy and pharyngoplasty group, and tonsillectomy alone group. In both groups, adenoidectomy was also performed in patients with adenoid hypertrophy. Differences in their healing processes in the pharyngeal wound and their hemorrhage proportions were compared. Furthermore, postoperative velopharyngeal function was also assessed. Results. Pharyngoplasty together with tonsillectomy was performed in 328 children with obstructive sleep apnea from tonsillar hypertrophy, and tonsillectomy was performed in 275 children. These cohorts did not reveal any significant demographic differences between groups. Furthermore, blood loss was found to be significantly decreased in the tonsillectomy and pharyngoplasty group (P <0.01), and the healing process was markedly shorter. Postoperative velopharyngeal function was not affected. Conclusions. Tonsillectomy in conjunction with pharyngoplasty reduced the duration of the healing process and blood loss, compared with tonsillectomy alone; however, postoperative complications did not increase. We consider pharyngoplasty in conjunction with tonsillectomy has great potential in the treatment of children with obstructive sleep apnea.

Postoperative characteristics of combined pharyngoplasty and tonsillectomy versus tonsillectomy in children with obstructive sleep apnea syndrome. / Características posoperatorias de la faringoplastia combinada con amigdalectomía en comparación con la amigdalectomía en niños con síndrome obstructivo de apnea del sueño.

PURPOSE: The study aims to identify the postoperative advantages of tonsillectomy in conjunction with pharyngoplasty and tonsillectomy alone in children with obstructive sleep apneas. METHODS: In a prospective observational study, patients who met the study criteria were randomly divided into two groups: tonsillectomy and pharyngoplasty group, and tonsillectomy alone group. In both groups, adenoidectomy was also performed in patients with adenoid hypertrophy. Differences in their healing processes in the pharyngeal wound and their hemorrhage proportions were compared. Furthermore, postoperative velopharyngeal function was also assessed. RESULTS: Pharyngoplasty together with tonsillectomy was performed in 328 children with obstructive sleep apnea from tonsillar hypertrophy, and tonsillectomy was performed in 275 children. These cohorts did not reveal any significant demographic differences between groups. Furthermore, blood loss was found to be significantly decreased in the tonsillectomy and pharyngoplasty group (P <0.01), and the healing process was markedly shorter. Postoperative velopharyngeal function was not affected. CONCLUSIONS: Tonsillectomy in conjunction with pharyngoplasty reduced the duration of the healing process and blood loss, compared with tonsillectomy alone; however, postoperative complications did not increase. We consider pharyngoplasty in conjunction with tonsillectomy has great potential in the treatment of children with obstructive sleep apnea.

Objetivo. Identificar las ventajas posoperatorias de la amigdalectomía en conjunto con la faringoplastia en comparación con la amigdalectomía sola en niños con apnea obstructiva del sueño. Métodos. En un estudio prospectivo observacional, los pacientes que cumplían con los criterios del estudio fueron asignados aleatoriamente a dos grupos: el grupo de amigdalectomía y faringoplastia, y el grupo de solo amigdalectomía. En ambos grupos, también se practicó adenoidectomía a los pacientes con vegetaciones. Se compararon los procesos de cicatrización en la herida faríngea y las proporciones hemorrágicas. Además, se evaluó la función velofaríngea posoperatoria. Resultados. La faringoplastia junto con la amigdalectomía se practicó en 328 niños con apnea obstructiva del sueño debido a hipertrofia amigdalina, y la amigdalectomía sola, en 275 niños. Estas cohortes no mostraban diferencias demográficas significativas. Por otro lado, se encontró que la pérdida de sangre fue significativamente menor en el grupo que recibió amigdalectomía y faringoplastia (p < 0,01), y el proceso de cicatrización fue notablemente más breve. La función velofaríngea posoperatoria no resultó afectada. Conclusiones. En comparación con la amigdalectomía, la amigdalectomía junto con la faringoplastia redujeron la duración del proceso de cicatrización y la pérdida de sangre; no obstante, las complicaciones posoperatorias no aumentaron. En nuestra opinión, la combinación de faringoplastia y amigdalectomía reúne un gran potencial en el tratamiento de los niños con apnea obstructiva del sueño.

Clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of OSAS children.

This study was designed to investigate the clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of children with obstructive sleep apnea syndrome (OSAS).One hundred ninety-five children were enrolled and divided into 3 groups: groups A, B, and C; the group A (oral use of montelukast sodium), group B (nasal spray of mometasone furoate), and group C (oral use of montelukast sodium + nasal spray of mometasone furoate). Telephone questionnaire surveys were carried out. Polysomnography monitoring was performed and lateral x-ray radiographs of the cervical spine were taken before treatment and at 12 weeks after treatment. The improvement of clinical symptoms after treatment and its effective rate were analyzed. The difference in clinical characteristics between groups C1 and C2 was analyzed.In the 3 groups, clinical symptoms improved at 12 weeks after treatment compared with before (P < .05 or P < .01). Apnea-hypopnea index value decreased (P < .05) and minimal SaO2 increased (P < .05), while adenoidal/nasopharyngeal ratio was reduced (P < .05). Compared with groups A and B, group C had a shortened response duration of snoring, apnea, and restless sleep (P < .05). Differences in the response duration of buccal respiration and hyperhidrosis were not statistically significant (P > .05). The total effective rate was higher in group C than in A and B (P < .05), while the differences in all indices between groups A and B were not statistically significant (P > .05). The difference in the grade of the size of the tonsil between groups C1 and C2 was statistically significant (P < .05).The total effective rate of the combined treatment was higher than that of the single use of any of the 2 drugs, which allowed the rapid relief of symptoms. Drug treatment may have a poor curative effect in the treatment of OSAS patients with ≥ grade 3 tonsil hypertrophy.

Effects of leukotriene D4 on adenoidal T cells in children with obstructive sleep apnea syndrome.

PURPOSE: This study aims to determine whether leukotriene D4 (LTD4) can promote T cell proliferation in adenoid tissues via activation of CysLT1 receptors in children with OSAS. METHODS: CD4+ and CD8+ T cell proliferation was assessed by flow cytometry in adenoid mononuclear cells (AdMCs) stimulated with LTD4 from children with OSAS. The activation of mitogen-activated protein kinase pathways and their effects on the proliferation of CD4+ and CD8+ T cells in AdMCs were observed by western blotting. RESULTS: LTD4 increased the proliferation rates of both phytohemagglutinin (PHA)-stimulated CD4+ T cells (15.5±8.4% in the PHA group vs. 24.8±6.3% in the PHA+LTD4 group; n=27; P<0.001) and CD8+ T cells (17.2±5.9% in the PHA group vs. 23.5±5.2% in the PHA+LTD4 group; n=27; P<0.05) in AdMCs. LTD4 (10-4 mmol) significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, but not c-Jun N-terminal kinases (JNK). The ERK1/2 inhibitor PD98059 significantly inhibited the proliferation of CD4+ and CD8+ T cells in LTD4-stimulated AdMCs. CONCLUSION: LTD4 regulates the proliferation of CD4+ and CD8+ T cells in PHA-stimulated AdMCs via upregulation of the ERK1/2 pathway. This finding indicates that CysLT1 receptors play a regulatory role in the pathogenesis of OSAS in children.

Hybrid gold-gadolinium nanoclusters for tumor-targeted NIRF/CT/MRI triple-modal imaging in vivo.

Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, we prepared hybrid gold-gadolinium nanoclusters (NCs), which are ultrasmall, stable, biocompatible, and suitable for triple-modal NIRF/CT/MRI imaging. Upon intravenously injected, the hybrid NCs are effectively accumulated in tumor tissues and quickly clear by renal excretion, indicating their capacity of tumor targeting and low body residues. Notably, the ultrasmall hybrid NCs would penetrate into the solid tumor for capturing its heterostructure and do not induce potential toxicity in vivo. Hence, the well-defined hybrid gold-gadolinium NCs provide a versatile nanoprobe for cancer targeted imaging and diagnosis in vivo.

Topology optimization of a novel stent platform with drug reservoirs.

The new generation of drug-eluting stents (DES) is required to control drug release kinetics. A novel DES (the Conor stent) with drug reservoirs on struts has been engineered. Topology optimization of one Conor stent strut was based on the commercial finite element analysis code OptiStruct, with the aim of increasing the strut stiffness while retaining its drug holding capacity. Results show that the element density distribution of the strut model was optimized with manufacturing constraints of extrusion constraint and minimum member size control. The optimal result was directly transformed to a clear, manufacturable design concept using the OptiStruct utility OSSmooth. The final manufacturing design increased the strut stiffness and yielded better stress distribution, as compared to the original strut design under the same loading. Topology optimization may help designers devise novel stent platforms for future DES with drug reservoirs and adequate scaffolding.

[Pharmacodynamics of China-made rapamycin-polylactide-co-glycolide peripheral arterial eluting stent membrane: in vitro experiment].

OBJECTIVE: To evaluate the property and drug releasing pattern of the China-made rapamycin-polylactide-co-glycolide (PLGA) peripheral arterial eluting stent membrane. METHODS: Rapamycin was put into PLGA so as to made rapamycin-PLGA complex. Twelve nickel-titanium self-expanding stents were dipped into the complex to make drug-eluting stents. Somatotype microscope was used to observe the macro-form of the surface of the eluting membrane, and atom force microscope was used to analyzing the three-dimensional appearance and surface roughness of the membrane. The stents were put into fluid with platelets to observe the form of platelets blood compatibility by scanning electron microscopy. The extra degradation of the coating layer, by putting the stents into a simulation system of internal environment. High efficacy liquid chromatography was used to study the pharmacokinetics of the stents. Standard curve and stimulative curve, and drug release curve of multiple stents were drawn and analyzed. RESULTS: The membranes of all 12 stents had smooth surfaces and regular thickness and no membrane falling-off was observed. The platelets on the surfaces of the stents were inactivated and the number of the platelets adhering to the surfaces of the stents were reduced obviously in comparison with the blank control. PLGA degraded by 20% within 2 weeks and then the degradation speed accelerated until complete degradation occurred within 6 weeks, and the drug releasing lasted more than 50 days. The percentage of accumulative drug release was 11.02% in 24 hours, 41.23% in 9 days, and 79.44% in 30 days. CONCLUSION: Smooth and even, and capable of controlling the drug release, rapamycin-PLGA peripheral arterial eluting stent membrane coating has the potential clinical value in preventing in-stent stenosis.

Delivery and release of nitinol stent in carotid artery and their interactions: a finite element analysis.

Carotid angioplasty and stenting (CAS) has emerged as an effective alternative to carotid endarterectomy, and nitinol stents are commonly used in CAS. To evaluate biomechanical properties of nitinol carotid stents and their interactions with carotid arteries, a finite element method (FEM) model was built which is composed of a stenotic carotid tissue, a segmented-design nitinol stent and a sheath. Two different stents were considered to show the influence of stent design on the stent-vessel interactions. Results show that the superelastic stents were delivered into the stenotic vessel lumen through the sheath and self-expanded in the internal and common carotid artery. The stent with shorter struts may have better clinical results and the different stent designs can cause different carotid vessel geometry changes. This FEM can provide a convenient way to test and improve biomechanical properties of existing carotid stents and give clues for new nitinol carotid stent designs.

Stent expansion in curved vessel and their interactions: a finite element analysis.

Coronary restenosis after angioplasty has been reduced by stenting procedure, but in-stent restenosis (ISR) has not been eliminated yet, especially in tortuous vessels. In this paper, we proposed a finite element method (FEM) to study the expansion of a stent in a curved vessel (the CV model) and their interactions. A model of the same stent in a straight vessel (the SV model) was also studied and mechanical parameters of both models were researched and compared, including final lumen area, tissue prolapse between stent struts and stress distribution. Results show that in the CV model, the vessel was straightened by stenting and a hinge effect can be observed at extremes of the stent. The maximum tissue prolapse of the CV model was more severe (0.079 mm) than the SV model (0.048 mm); and the minimum lumen area of the CV was decreased (6.10 mm(2)), compared to that of the SV model (6.28 mm(2)). Tissue stresses of the highest level were concentrated in the inner curvature of the CV model. The simulations offered some explanations for the clinical results of ISR in curved vessels and gave design suggestions of the stent and balloon for tortuous vessels. This FEM provides a tool to study mechanisms of stents in curved vessels and can improve new stent designs especially for tortuous vessels.

Degradation of porous poly(D,L-lactic-co-glycolic acid) films based on water diffusion.

Poly(D,L-lactic-co-glycolic acid) has been extensively used as a controlled release carrier for drug delivery due to its good biocompatibility, biodegradability, and mechanical strength. Effects of dense and porous film's degradation behavior have been systematically investigated up to 17 weeks in Hank's Simulated Body Fluid at 37 degrees C. The degradation of the films was studied by measuring changes in weight, molecular weight and its distribution, morphology, composition etc.. A special thing was that the differences in water diffusion in dense and porous structure films caused the different degradation behavior. According to the characteristic changes of various properties of films, the degradation process is suggested to be roughly divided into four stages, tentatively named as water absorption stage, dramatic loss of molecular weight or micro-pores formed stage, loss of weight or enlarged-pores formed stage, pores diminished or pores collapse stage.

Corrosion resistance of a laser spot-welded joint of NiTi wire in simulated human body fluids.

The purpose of this study was to investigate corrosion resistance of a laser spot-welded joint of NiTi alloy wires using potentiodynamic tests in Hank's solution at different PH values and the PH 7.4 NaCl solution for different Cl- concentrations. Scanning electron microscope observations were carried out before and after potentiodynamic tests. The composition of a laser spot-welded joint and base metal were characterized by using an electron probe microanalyzer. The results of potentiodynamic tests showed that corrosion resistance of a laser spot-welded joint of NiTi alloy wire was better than that of base metal, which exhibited a little higher breakdown potential and passive range, and a little lower passive current density. Corrosion resistances of a laser spot-welded joint and base metal decreased with increasing of the Cl- concentration and PH value. The improvement of corrosion resistance of the laser spot-welded joint was due to the decrease of the surface defects and the increase of the Ti/Ni ratio.

Analysis of the transient expansion behavior and design optimization of coronary stents by finite element method.

The percutaneous transluminal coronary angioplasty (PTCA) assisted with stenting technique has become a primary therapy to coronary heart disease. In practice, the structure conditions of both ends of stent/balloon system influence a stent's instantaneous expansion behavior. The transitory nonuniform expansion, the so-called dogboning, of stent/balloon system is one of the main reasons to induce the acute vascular injury at the two edges of a stent. This kind of vascular injury has a close relationship with the in-stent restenosis. In the present paper, the finite element method (FEM) was applied to simulate the transient expansion process of stent/balloon system with different stent structure and balloon length under the internal pressure. And two types of stent and six collocations of stent and balloon were modeled. Modeling results showed that the dogboning phenomenon can be eliminated by improving geometry of a stent or/and varying the length of balloon over stent. The above modeled results were further confirmed by following in situ observation.

[The expression of c-fos and transmitter calcitonin gene-related peptide in the chronic compressive injury of the nerve root].

OBJECTIVES: To investigate the significance of c-fos oncogene morphogenetic protein's locational expression, and the correlativity between nerve transmitters calcitonin gene-related peptide (CGRP) expression and nerve root's functional change using the animal model of the chronic compressive injury in the nerve root. METHODS: The animal model of chronic compressive injury of the nerve root was established by transplanting autogenous cancellous bone into the intervertebral foramen. During different injury phase (1, 2, 4, 8, 12, 24 weeks after operation), the functional status of the nerve root was determined under the monitoring of evoked potential, and the expression changes of c-fos oncogene morphogenetic protein and nerve transmitter CGRP were detected using in situ hybridization technique and their expression intensity was determined using automatic image analytic instrument respectively. RESULTS: One week after operation, the c-fos expression strengthened in both anterior and posterior root fiber obviously. Two to four weeks after operation, the expression of the posterior root fiber weakened than the anterior root fiber. After 12 weeks, the anterior root fiber expression turned down obviously, however the posterior root fiber expression backed up slightly compared with that of the 8 weeks. By the time of 24 weeks after operation, the expression enhancement in all roots disappeared. CGRP expression increased obviously at the site of compressive axon of both anterior and posterior root. The expression of the posterior root axon and ganglion cell was higher than that of the anterior root axon. CGRP expression was diminished in the second week than the first week, and that was especially obvious in the posterior root and ganglion cell. But 4 weeks after operation, the expression enhanced once more, and that was more obvious inside the anterior root axon. Eight weeks after operation, the expression intensity attained the high peak. Twelve weeks after operation, the expression started the slow-moving descent. CONCLUSIONS: The expression of c-fos gene protein is beneficial to localize the damaged part of certain nerve. During chronic injury, the degeneration of posterior root sensory fiber is earlier than the anterior root motor fiber. The expression of CGRP strengthened when the nerve fiber degenerated by the harmful stimulation, and the expression intensity is positively related with pain. That suggests when the nervous tissue is hurt, the information of warning and regulation should be sent out to our body.