Inhibition of neointimal hyperplasia in balloon-induced vascular injuries in a rat model by miR-22 loading Laponite hydrogels.

Percutaneous coronary intervention (PCI) is the mainstream treatment to widen narrowed or obstructed coronary arteries due to pathological conditions. However, the post-operational neointimal hyperplasia occurs because of endothelium denudation during surgical procedures and the following inflammation. MicroRNAs (miRs) are new therapeutics of great potential for cardiovascular diseases. However, miRs easily degrade in vivo. A vehicle that can maintain their bioactivities and extend their retention at the site of delivery is prerequisite for miRs to play their roles as therapeutic reagents. Here, we reported the use of the Laponite hydrogels to deliver miR-22 that are modulators of phenotypes of smooth muscle cells (SMCs). The Laponite hydrogels allow a homogenous distribution of miR-22 within the gels, which had the capacity to transfect SMCs in vitro. Upon the injection of the miR-22 incorporated in the Laponite hydrogels in vivo, miR-22 could be well retained surrounding arteries for at least 7 days. Moreover, the miR-22 loading Laponite hydrogels inhibited the neointimal formation, reduced the infiltration of the macrophages, and reversed the adverse vascular ECM remodeling after the balloon-induced vascular injuries by upregulation of miR-22 and downregulation of its target genes methyl-CpG binding protein 2 (MECP2). The application of the Laponite hydrogels for miR local delivery may offer a novel strategy to treat cardiovascular diseases.

Pressure pain threshold and somatosensory abnormalities in different ages and functional conditions of post-stroke elderly.

BACKGROUND: Somatosensory deficits and abnormal pain sensitivity are highly prevalent among stroke survivors, which negatively impacts their quality of life and recovery process. However, the factors for pressure pain threshold (PPT) and somatosensory abnormalities in post-stroke elderly remain unknown. The aim of this study was to explore the effects of age, side and other functional conditions, such as spasticity and motor functions, on PPT and sensory abnormalities among elderly after stroke. METHODS: The cross-sectional study finally included 43 post-stroke elderly aged over 60 and assessed the PPT of 14 bilateral muscles widely located in the whole body by using a digital force gage. Meanwhile, spasticity, motor function, joint pain and activity of daily living (ADL) were evaluated by the Modified Ashworth scale, Fugl-Meyer, and Barthel Index, respectively. All participants were divided into higher-aged and lower-aged groups based on the median age of all of them. RESULTS: Higher age tended to be associated with higher sensitivity but not significant except for one upper limb muscle, and the affected side showed significantly higher PPTs than the unaffected side in three out of seven muscles (p < 0.05). Furthermore, the somatosensory abnormalities in the affected side, particularly hypoalgesia, were more frequent in higher-aged than lower-aged patients in most assessed muscles. Meanwhile, patients with spasticity showed more increment of PPTs in affected muscles around the knee joint than patients without spasticity (p < 0.05). Patients with better motor functions, less joint pain and higher ADL performed less bilateral differences of PPTs than other patients in some muscles (p < 0.05). CONCLUSIONS: The age and side differences of mechanical pain sensitivity were found among post-stroke elderly. Older patients show higher sensitivity in both sides compared with the younger ones, and the affected side of the elder shows more somatosensory abnormalities, particularly hypoalgesia, than that of the younger ones. Post-stroke elderly in good functional conditions, such as normal muscle tone, better physical function and daily activities, and less joint pain, seems to have more equal pain sensitivity between both sides than those in poor conditions.

Intra-rater and inter-rater reliability of pressure pain threshold assessment in stroke patients.

BACKGROUND: As pain is a common symptom following a stroke, pressure pain threshold (PPT) assessment can be used to evaluate pain status or pain sensitivity of patients. However, the reliability of PPT test in stroke patients is still unknown. AIM: To examine the intra- and inter-rater reliability of PPT measurements in poststroke survivors and explore their factors. DESIGN: An observational study. SETTING: The setting of the study is a rehabilitation hospital. POPULATION: The population of the study was represented by a total of 54 patients after stroke. METHODS: The study included 16 measured points on the affected and unaffected sides. PPT was assessed by two raters in turn. Intra- and inter-rater reliability was evaluated by intraclass correlation coefficients (ICC). RESULTS: All intra-rater (ICC=0.84-0.97) and inter-rater (ICC=0.83-0.95) reliability for PPT assessment were good or excellent in stroke patients. Of the 16 points, 12 showed higher intra-rater ICC values than inter-rater, whereas no evident difference was observed between the affected and unaffected sides. Furthermore, patients who were male, ischemic, or with higher motor function generally performed higher ICC values than those who were female (24 out of 32 results), hemorrhagic (28 out of 32 results), or mobility dysfunction (26 out of 32 results), respectively. CONCLUSIONS: PPT assessment with good or excellent reliability can be used in stroke patients. Neither of the two sides (affected or unaffected) affects PPT reliability, and intra-rater reliability is better than inter-rater reliability. In addition, gender, stroke type, and motor function can affect the reliability of measuring mechanical pain threshold in poststroke survivors. CLINICAL REHABILITATION IMPACT: The pressure algometer can be used as a reliable and portable tool to assess the mechanical pain tolerance and sensory function in stroke patients in clinics.

The Effects of Gender, Functional Condition, and ADL on Pressure Pain Threshold in Stroke Patients.

BACKGROUND: Somatosensory impairments and pain are common symptoms following stroke. However, the condition of perception and pain threshold for pressure stimuli and the factors that can influence this in individuals with stroke are still unclear. This study aimed to investigate the gender differences in pressure pain threshold (PPT) and positive somatosensory signs for pressure stimuli, and explore the effects of joint pain, motor function, and activities of daily living (ADL) on pain threshold in post-stroke patients. DESIGN: A cross-sectional study. METHODS: A total of 60 participants with stroke were recruited, and their pain condition, motor functions, and ADL were evaluated by the Fugl-Meyer assessment of joint pain scale, motor function scale, and Barthel index, respectively. PPTs in eight tested points at the affected and unaffected sides were assessed. RESULTS: Significant differences in PPTs were found between male and female patients in all measured muscles (p < 0.05). Positive somatosensory signs for pressure stimuli, including hypoalgesia and hyperalgesia, were frequently found at the affected side, particularly in the extremity muscles, but such signs were not significantly influenced by gender (p > 0.05). More equal PPTs between both sides and relatively lower PPTs at the affected side in the trunk and medial gastrocnemius muscles (p < 0.05) were observed in patients with less pain, better motor functions, and ADL. CONCLUSION: Gender differences widely exist in post-stroke survivors either at the affected or unaffected side, which are multifactorial. Sensory loss and central and/or peripheral sensitization, such as hypoalgesia and hyperalgesia for pressure stimuli, caused by a brain lesion are common signs in male and female stroke patients. Moreover, patients who are in a better condition show a more symmetrical pain sensitivity between both sides in the trunk and in female lower extremities, indicating the bidirectional improvement of somatosensory abnormalities caused by a possible neural plasticity.

Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation.

Senescence is an irreversible growth arrest which can be triggered by stresses such as oxidative reaction, telomere shortening, DNA damage, or oncogene signaling. Oxidative stress accelerates vascular endothelial cell senescence, and may promote atherosclerosis in humans. Interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis, and has close relationship with oxidative stress. The objective of this study was to determine if IL-8 might be able to prevent oxidative stress-induced senescence of endothelial cells and the mechanisms. Human umbilical vein endothelial cells (HUVECs) were cultured and stimulated with hydrogen peroxide in the absence or presence of IL-8. After ex vivo cultivation, HUVECs became senescent as determined by acidic beta-galactosidase staining. IL-8 dose-dependently inhibited the onset of HUVEC senescence. Western blots indicated that IL-8 attenuated the oxidative stress induced high-expression of cell cycle regulation protein and inhibited the activation of p38 and NF-κB pathway. IL-8 also increased telomerase activity which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT), whereas these effects were significantly attenuated by SB 225002 (selective non-peptide CXCR2 antagonist). In conclusion, IL-8 exerted protective effects against endothelial senescence, which may be related to the activation of telomerase.

[Comparison of anti-inflammatory effect and analysis of astilbin red and white transverse section Smilax glabra in 28 collection sites].

OBJECTIVE: Astilbin in 28 Smilax glabra (red and white cross-section) from different sources was determined by HPLC. Pharmacodynamics and component of S. glabra was investigated through inflammation experiment (penetration type). METHOD: The analysis was performed on a Hypersil ODS2 column (4.6 mm x 250 mm, 5 microm) with the mobile phase of acetonitrile and 0. 1% acetic acid aqueous (21: 79) at a flow rate of 1.0 mL x min(-1). The detection wavelength was 291 nm, and the column temperature was 25 degrees C. Anti-inflammatory effect was compared from two type cross-section of Smilax glabra in capillary permeability experiment. RESULT: Linear correlation was good in the range of 0.003 379-4.004 microg, and the average recoveries were 100.1%, 101.9%, 99.3%, respectively. The content of astilbin in white and red transverse section were 0.19%-2.46% and 2.10%-5.92%, respectively. Anti-inflammatory efficiency of sectioned red and white were were 21% and 32%, respectively. CONCLUSION: Astilbin content and anti-inflammatory effect is significantly different between red and white transverse section of S. glabra, the content of astilbin is not positively related with anti-inflammatory effect.

[Hair cells apoptosis and the activation of P53 protein in intensive impulse noise induced cochlear lesion].

OBJECTIVE: To explore the pattern of hair cell injury and expression of P53 apoptosis protein in intensive impulse noise injured cochlear hair cells in guinea pigs. METHODS: Twelve adult guinea pigs were exposed to a series of 40 pairs of impulse noise (2 second intervals) at the intensity of 168 dB (SPL). Animals were terminated at 3, 6 and 12 hours after noise exposure, respectively. Cochlear surface preparations were performed with a double staining of FITC-conjugated phalloidin and propidium iodide for the observations of the stereocilia and the nucleus. P53 immunochemical staining was also performed 12 hours post-noise exposure to observe if there was expression of p53 protein in injured hair cells. Results Three hours after noise exposure, the outer hair cells at the end of basal turn and beginning of second turn were destroyed first with a character of nuclear condensation. Six hours post-noise exposure, many hair cells in the center of damage region had nuclear fragmentations, and the damaging area expanded towards to basal turn and apical turn. Twelve hours after noise exposure, the nucleus in most outer hair cells and inner hair cells at the region of damage center were missing. The nuclear condensation and fragmentation were appeared in hair cells in both sides of the center region of degeneration. P53 immunoreactive products were also found in damaged hair cells, not only in the central damage area, but also in the basal turn and the third turn. CONCLUSIONS: Intensive impulse noise resulted in apoptosis of cochlear hair cells that initiated between the end of basal turn and the beginning of second turn. Hair cell degeneration spread to basal and third turn along the basilar membrane. P53 may play an important role in impulse noise induced-hair cell apoptosis.

[Endonasal anatomy of lacrimal sac and its clinical significance in dacryocystorhinostomy].

OBJECTIVE: To explore the intranasal surface localization of the lacrimal sac in endoscopic dacryocystorhinostomy. METHODS: Fifteen adult cadavers (30 sides) were studied, the data of projection position of the lacrimal sac on the lateral wall of nasal cavity were measured. RESULTS: In 2/3 cadavers, the lacrimal sac is located above the axilla of the middle turbinate, and 1/3 lies below it. A majority of the lacrimal sac (2/3) are located below the entry point of the common lacrimal canaliculus, about 1/3 lies above it. Inner canthal ligament projects on the middle of the lacrimal sac, almost equal to the level of common lacrimal canaliculus. Thirty-two cases (thirty-nine sides) of chronic dacryocystitis were followed-up > 6 months after operation. Thirty-five sides were cured, 2 sides improved and 2 sides ineffective. The cure rate was 89.8%, improve rate 5.1% and ineffective rate 5.1%, respectively, and the total effective rate was 94.9%. CONCLUSIONS: The central position of dacryocystorhinostomy should be 0.2 cm above the front of the axilla of the middle turbinate, to make an curved mucous membrane incision 0.8 cm above and 0. 4 cm below the front of the axilla of the middle turbinate and bone ostium about 1.2 cm x 1.0 cm. It is the best position in endoscopic dacryocystorhinostomy. Locating the inner canthal ligament with a bayonet type forceps to find the projection of lacrimal sac is also a simple and easy method.

[Nerve exploration and decompression for traumatic recurrent laryngeal nerve injuries induced by thyroid gland surgery].

OBJECTIVE: To show the findings of recurrent laryngeal nerve injury exploration and find out therapeutic effects, indications and timing of nerve decompression for traumatic recurrent laryngeal nerve injury induced by thyroid gland surgery. METHODS: In this study there were 87 patients with recurrent laryngeal nerve injury, including 65 for nerve exploration and 22 for nonsurgical treatment. During nerve exploration, the types, severity of laryngeal nerve injuries and laryngeal muscular mass were studied. Nerve decompression was performed in these 14 patients whose compressing sutures or compression due to cicatricial hypertrophy were received nerve decompression. RESULTS: Injuries caused by thyroid gland operations mostly are of suture ligation (43%) and nerve severance (48%); simple scar compression was found only in 6 cases (9%). Atrophy of the laryngeal muscles was not very serious in patients with a course less than 6 months. In 10 patients with a course less than three months, nerve decompression restored normal functional abductor and abductor motion of the vocal cord in 9 patients and had no effects in one. Although functional motion of vocal cord was not seen in one case with a course less than 3 months and 4 cases between 3 and 5 months, the mass and tension of the reinnervated vocal cord became much the same as the contralateral normal vocal cord, thus resuming symmetric vibration of the vocal cords and physiological phonation. Although nonsurgical treatment improved severe hoarseness, it didn't restore normal functional motion of the vocal cord and normal voice. CONCLUSIONS: Nerve exploration showed a primary rule for recurrent laryngeal nerve injury induced by thyroid gland surgery. Early and mid-stage recurrent laryngeal nerve exploration and decompression may restore normal motion of the glottis, and it suggested laryngeal delayed reinnervation may help patients with a course more than 6 months.

[Long-term follow-up of autogenous fat injection for unilateral vocal cord paralysis].

OBJECTIVE: To study the long-term results of autogenous fat injection for unilateral vocal cord paralysis. METHODS: Twenty cases with unilateral vocal cord paralysis were treated by autogenous fat injection into the thyroarytenoid muscle to achieve medialization. The patients were divided into 3 groups by hoarse degree before operation, all of them were followed more than 12 months with serial video laryngoscope and voice evaluation. The ratio between paralyzed vocal cord upper surface and that of the normal vocal cord were adopted as the measurement for the vocal cord volume changes before and after operation. RESULTS: 1. The volume of paralyzed vocal cord was increased. The degree of hoarse and normalized noise energy (NNE) were evaluated by objective methods after operation. 2. The hoarse symptom was less severe after operation than that before operation. The cure cases 3 to 6 months and over 12 months after operation were nearly the same. 3. NNE of over 12 months and 3 to 6 months after operation were not significantly different, but the postoperative NNE were different with that before operation. CONCLUSIONS: Autologous fat injection was an effective method for treating unilateral vocal cord paralysis, and the long term effects were reliable.

[Diagnosis and management of sulcus vocalis].

OBJECTIVE: To clarify the pathophysiology of sulcus vocalis and to develop a more rational approach to treatment. METHODS: Twenty-nine cases of sulcus vocalis patients were divided into three classification: Type I is a physiologic variant and no dysphonia (11 cases). Types II (sulcus vergeture, 13 cases) and III (sulcus vocalis, 5 cases) are characterized by severe dysphonia and loss of vibratory activity. Eighteen cases of dysphonia were treated by surgery and phonation training. The operations included fat injection into vocal cords (9 cases of types II and 1 cases of types III, including 1 case of types III of second operation), fat implantation into sulcus vergeture after incision (4 cases of types II and 1 cases of types III) and undermining of the mucosa and sulcus vocalis resection (4 cases of types III, including 1 case of second operation). Phonatory function and video laryngostroboscopic data were evaluated before and after surgery and phonation training treatment in 18 patients. The mean follow-up time was 15.3 months. RESULTS: Ten cases of types II had excellent results after fat injection into vocal cords (n = 6) and fat implantation into sulcus vergeture after incision (n = 4). Three cases of types II improved after fat injection into vocal cords. Three cases of type III had excellent results after sulcus vocalis resection. One case of type III had excellent results by Second operation (sulcus vocalis resection) after fat injection into vocal cord. One case of type III improved by Second operation (fat injection into vocal cords) after fat implantation into sulcus vergeture after incision. No postoperative complications were noted. CONCLUSION: Accurate classification of sulcus vocalis is important and then adapt treatment to different types. Fat implantation into sulcus vergeture to type II and sulcus vocalis resection to type III were the best choice methods.