MicroRNA-204 silencing relieves pain of cervical spondylotic radiculopathy by targeting GDNF.

Cervical spondylosis may cause chronic neck pain, radiculopathy and/or myelopathy, and consequently results in severe brain damage. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. Accumulating microRNAs (miRNAs) have highlighted as critical regulators of GDNF signaling in the mediation of neuroinflammation and neuropathic pain. Hence, we performed this study to investigate the potential role of miR-204 in the neuropathic pain of cervical spondylotic radiculopathy (CSR) by targeting GDNF. A rat model of spinal cord compression (SCC) was established to stimulate a pathologic lesion. RT-qPCR and western blot assays characterized the downregulation of GDNF and the upregulation of miR-204 in spinal cord tissues of rats under the conditions of SCC. Moreover, miR-204 could directly target GDNF, as evidenced by dual-luciferase reporter gene assay. In order to elucidate the roles of miR-204 and GDNF in SCC-induced neuropathic pain, miR-204 sponge, GDNF, or shRNA against GDNF was introduced to the rats, followed by measurements for SCC-induced neuroinflammation and neuropathic pain. GDNF upregulation or miR-204 silencing was identified to reduce the spontaneous pain score, gait scores and cell apoptosis. Furthermore, GDNF upregulation or miR-204 silencing resulted in elevated amplitude of sensory-evoked potentials (SEPs), number of motoneurons, release of pro-inflammatory factors, TNF-α, and IL-1ß in addition to an increase in the anti-inflammatory factor BDNF. Taken together, upregulation of GDNF induced by miR-204 silencing confers protection against SCC-induced pain in rat models, suggesting a potential therapeutic target for CSR treatment.

Radiofrequency Thermocoagulation in Relieving Refractory Pain of Knee Osteoarthritis.

To investigate the efficacy of radiofrequency thermocoagulation (RFTC) in relieving refractory pain of knee osteoarthritis (OA), we selected 54 patients with chronic knee OA pain, 27 treated with RFTC (case group) and 27 receiving regular treatments (control group). Response evaluations were conducted before treatment, and at the termination of treatment, and 3-month follow-up, applying the visual analog scale, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and American Knee Society Score (AKSS). Data analyses were performed with SPSS 21.0. At the termination of treatments and 3-month follow-ups, cases gained significantly increased scores in vitality, bodily pain, general health perceptions, physical functioning, and social role functioning by SF-36 scaling and in pain, range of motion, stability, walking, and stair climbing by AKSS (all P < 0.05). Controls received higher scores by AKSS in pain at the termination of treatments and in pain, range of motion, and walking at the termination of 3-month follow-ups (all P < 0.05). Both cases and controls presented significant difference between visual analog scale scores before treatments and those at the termination of 3-month follow-ups (both P < 0.05). All patients felt less pain after treatments, cases presenting better improvement (P < 0.05). Pain was stronger in females compared with males and in a positive correlation with age while had no obvious relation to disease course. In conclusion, RFTC may have better efficacy in relieving refractory pain and promoting function recovery in patients with knee OA than regular treatment.

The Reinfusion of Autogenous Shed Blood After Unilateral Total Knee Arthroplasty Using the Perioperative Autologous Transfusion System OrthoPAT.

This study aims to explore the use of postoperative autogenous shed blood reinfusion using Orthopedic Perioperative Autotransfusion System (OrthoPAT) system in treating patients undergoing unilateral total knee arthroplasty (TKA). Fifty patients undergoing unilateral TKA were enrolled as the experimental group A and were treated with reinfusion of autologous shed blood within 6 hours after unilateral TKA using OrthoPAT. Accordingly, 50 patients undergoing unilateral TKA were selected as the experimental group B and were treated with allogeneic blood transfusion. Different indexes were observed at different times. Patients in both groups had relatively stable hemodynamics, and there was no postoperative coagulopathy. Prothrombin time, thrombin time, and activated partial thromboplastin time were lower, and fibrinogen was higher in group A than that in group B 24 hours after surgery (all P < 0.05). White blood cell, red blood cell, hemoglobin, hematocrit (Hct), and platelet count levels in group A were lower than those in group B 12 hours after surgery (all P < 0.05). The postoperative complications of the 2 groups have significant difference (P < 0.05). Postoperative autogenous shed blood reinfusion using OrthoPAT system in the treatment of patients undergoing unilateral TKA may improve the coagulation function of patients and reduce the rejection caused by standard allogeneic blood transfusion.

Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology.

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4(tm1Dontuh/tm1Dontuh) mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4(tm1Dontuh/tm1Dontuh) mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4(tm1Dontuh/tm1Dontuh) mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4(tm1Dontuh/tm1Dontuh) mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4(-/-) mice and Slc26a4(loop/loop) mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains.

Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice.

Diabetes mellitus can be treated with islet transplantation, although there is a scarcity of donors. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord stroma could be induced to differentiate into insulin-producing cells and the effects of retro-orbital injection of human insulin-producing cells for the treatment of nonobese diabetic (NOD) mice. MSCs were isolated from human umbilical cord stroma and induced to differentiate into insulin-producing cells using differentiation medium. Differentiated cells were evaluated by immunocytochemistry, RT-PCR, and real-time PCR. C-peptide release, both spontaneous and after glucose challenge, was measured by ELISA. Insulin-producing cells were then transplanted into NOD mice. Blood glucose levels and body weights were monitored weekly. Human nuclei and C-peptide were detected in mouse livers by immunohistochemistry. Pancreatic ß-cell development-related genes were expressed in the differentiated insulin-producing cells. Differentiated cells' C-peptide release in vitro increased after glucose challenge. Further, in vivo glucose tolerance tests showed that blood sugar levels decreased after the cells' transplantation into NOD mice. After transplantation, insulin-producing cells containing human C-peptide and human nuclei were located in the liver. Thus, we demonstrated that differentiated insulin-producing cells from human umbilical cord stromal MSCs transplanted into NOD mice could alleviate hyperglycemia in diabetic mice.

[Clinical assessment of ProSeal laryngeal mask airway during total hip replacement operation].

OBJECTIVE: To assess the value of ProSeal-LMA (laryngeal mask airway) during hip replacement operation. METHODS: Sixty patients undergoing hip replacement operation were randomly divided into two groups with 30 cases in each. ProSeal-LMA was applied in Group I and normal endotracheal tube in Group II. The parameters of heart rate (HR), mean arterial blood pressure (MAP), partial pressure of carbon dioxide in end expiratory gas (PetCO2) and airway pressure (Paw) were monitored and recorded in both groups at time points of before and after placing ProSeal-LMA or tracheal tube, body turning-over, skin incision and extubating of ProSeal-LMA or tracheal tube. And also the cases with airway complications were reported. RESULTS: There was no significant changes of HR and MAP in Group I at time points of placing and extracting ProSeal-LMA (P > 0.05). However, there was significant difference of HR and MAP in Group II at time points of placing and extracting tracheal tube (P < 0.05), And it was significantly higher than that in Group I at the same time point (P < 0.05). No significant difference of these parameters was observed at other time points (P > 0.05). And also PetCO2 and Paw were not changed significantly between two groups at time points of before and after body turning over (P > 0.05). CONCLUSION: ProSeal-LMA can be applied in hip replacement operation because of its simple handling, lesser effects upon respiration and circulation and fewer post-operative complications.