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Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
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Mice , Animals , Diabetes Mellitus, Experimental/metabolism , Axons/physiology , Diabetic Neuropathies , Sensory Receptor Cells/metabolism , Neuralgia/metabolismABSTRACT
Objective To investigate the expression and clinical significance of TM9SF3 in lung adenocarcinoma (LUAD). Methods TCGA and GEPIA databases were used to screen the differentially-expressed TM9SF family molecules and analyze their effects on patient prognosis with LUAD. The expression and localization of TM9SF3 in LUAD patients were verified by a human proteomic mapping database, Western blot assay, and polymerase chain reaction assay. Herein, the GSEA was used for the signal pathway enrichment analysis of TM9SF3-related genes. Meanwhile, the TIMER database and CIBERSORT algorithm were used to analyze the correlation between differentially-expressed TM9SF3 and the degree of immune cell infiltration. Results The expression of TM9SF3 in LUAD was significantly increased and had a significant adverse effect on the prognosis of LUAD patients. In addition, immunoblotting and polymerase chain reaction confirmed that TM9SF3 was highly expressed in LUAD. Meanwhile, the genes related to TM9SF3 expression were mainly enriched in cell signaling pathways regulating immune cell activity. The expression of TM9SF3 was significantly correlated with the expression changes of six immune cells. Conclusion TM9SF3 is differentially expressed in LUAD and may be used as a potential prognostic marker for LUAD patients. TM9SF3 can also change the level of immune cell infiltration in LUAD patients and is expected to be a new potential target for LUAD immunotherapy.
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Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.
Subject(s)
Animals , Male , Rats , Acoustic Stimulation , Analysis of Variance , Dose-Response Relationship, Drug , Electroencephalography , Excitatory Amino Acid Antagonists , Pharmacology , Gamma Rhythm , Ketamine , Pharmacology , Prefrontal Cortex , Rats, Sprague-Dawley , Sensory Gating , Sleep Stages , Statistics as Topic , Time Factors , WakefulnessABSTRACT
Objective To investigate the effect of transient receptor potential M4 (TRPM4) on autonomous regulation disorder of cerebral blood flow following subarachnoid hemorrhage (SAH) in rats.Methods A total of 120 clean grade male SD rats were selected.They were divided into sham operation,SAH,negative control,and treatment groups according to the random number table.The dead rats were excluded.A SAH model was induced by using the suprasellar cistern injection method with a stereotaxic apparatus.Isotonic saline 0.2 ml was injected into the rats of the sham operation group and negative control group respectively,and autologous tail arterial blood 0.2 ml was injected into the rats of the SAH group and the treatment group respectively.The isotonic saline solution was continuously pumped into lateral ventricle of rats via implantable micro-pump in the sham operation group and the SAH group respectively,and the concentration of 0.03 mol/L of TRPM4 blocking agent was continuously pumped into the lateral ventricles of rats in the control group and the treatment group respectively.The 4 groups of rats received the regional cerebral blood flow and whole cerebral blood flow detection on day 3,5,and 7,respectively.Results One hundred and six (88.3%) of the 120 SD rats survived to the time point of study,data analyses were performed in the 4 groups (with 21 rats in each group) respectively (n=7 in each time point).There were significant differences in cerebral cortex local and whole cerebral blood flow at day 3,5,and 7 in the sham operation,SAH and negative control groups (all P<0.05).Cerebral cortex local cerebral blood flow (141±18,148±24,and 168±19 PU,respectively at day 3,5,and 7) and whole cerebral blood flow (93±5,85±5,and 85±6 ml/[100 g·min],respectively at day 3,5,and 7 in the SAH group) were decreased significantly compared with the sham operation group (cortex local cerebral blood flow:235±17,220±24,and 224±20 PU),whole cerebral blood flow (141±10,147±8,and 143±8 ml/[100 g·min]),all P<0.05).Cerebral cortex local and whole cerebral blood flow (cortical local cerebral blood flow:183±26,173±26,and 187±15 PU,whole brain:114±10,104±9,and 119±5 ml/(100 g·min) in the treatment group were significantly increased compared with the SAH group (all P<0.05).Conclusion TRPM4 has an obvious effect on improving the autonomous regulation disorder of cerebral blood flow after SAH.
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Objective To summarize treatment experiences of microsurgical clipping for anterior communicating artery aneurysm via pterional approach.Methods Clinical data of 82 cases undergoing microsurgical clipping for anterior communicating artery aneurysm via pterional approach in the first affiliated hospital of Kunming Medical University from October 2008 to December 2014 were collected and retrospectively analyzed.The patients were divided into different groups by Hunt-Hess illness grading scale,with 11 cases for level 0,7 cases for level Ⅰ,30 cases for level Ⅱ,25 cases for level Ⅲ,8 cases for level Ⅳ,and 1 cases for level Ⅴ.Twenty-one patients underwent operation at early stage of SAH (＜3d),15 at late stage of SAH (4d～2W),and 35 at prolonged stage of SAH (＞2W).The prognosis of patients was evaluated according to GOS classification criteria at discharge.Results A total of 85 ACoAA were found in 82 patients and all of them were clipped and,at the same time,3 aneurysms were resected and 11 thrombuses were punctured,cut and removed.In the operation,15 (17.6％) aneurysms ruptured again and temporary blocking happened for 73 times,with the shortest blocking time of 2 rmin,the longest of 40 rmin,and the average of 9.26min.According to GOS score,good recovery rate was 79.3％ (65/82),moderate disability rate was 12.2％ (10/82),severe disability rate was 3.7％ (3/82),vegetative state rate was 0％,and death rate was 4.9％ (4/82).Good recovery rates for the operations at early,late and prolonged stage of SAH were 85.7％,73.3％ and 82.3％ respectively and for level 0 to level Ⅴ were 90.9％,85.6％,86.7％ and 84.0％,25.0％ and 0.0％ respectively.Results of DSA or CTA re-examination upon 55 patients followed-up at discharge or three months after discharge showed that tumor pedicle were clipped and aneurysm disappeared.Fifty cases were followed up from four months to seven years after the operation,with one case of aneurysm recurrence.Another thirty-two cases were lost to follow-up.ConclusiornS Microsurgical techniques and microdissection are keys to successful operation.Pterional approach can guarantee successful clipping of aneurysms with different directions,locations and sizes.It is also an easy,effective and reliable approach with less postoperative complications.Operation for anterior communicating artery aneurysm should be performed as early as possible.
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Objective To study the effect of spontaneous subarachnoid hemorrhage (SAH)on transient receptor potential melastatin 4 (TRPM4)channel activity. Methods Seventeen SD rats of clean grade were selected. They were randomly divided into either a SAH (n = 10)or a sham operation group (n = 7) according to the random number table. At day 5 after SAH modeling,the cerebral arteries were harvested and the cerebral arterial smooth muscle cells were isolated using enzymatic digestion method. Western blot was used to detect TRPM4 expression and translocation rate. Patch-clamp techniques were used to study the maximum current intensity of the TRPM4 single channel in cerebral arterial smooth muscle cells. Results The fluorescent-stained TRPM4 were observed in cerebral arterial smooth muscle cells in the 2 groups of rats. The relative quantities of TRPM4 in the total protein of the sham operation group and the SAH group were 24 ± 3% and 32 ± 4% respectively. There was significant difference between the 2 groups (t = 4. 47,P 0. 05). Conclusion SAH has the induced effect for TRPM4 activity.
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Objective:To investigate the effect of BMSCs transplantation plus hyperbaric oxygen (HBO) on repair of rat SCI. Methods:Seventy five male rats were divided randomly into five groups:sham, vehicle, BMSCs transplantation group, combination group, 15 rats in each group. Every week after the SCI onset, all animals were evaluated for behavior outcome by Basso-Beattle-Bresnahan (BBB) score and inclined plane test. Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset. HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results:Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment. Results from histopathology showed favorable recovery from combination group than other treatment groups. The number of BrdU+ in combination group were measureable more than transplantation group (P<0.05). The greatest decrease in TNF-α, IL-1β, IL-6, IFN-αdetermined by Elisa assay in combination group were evident too. Conclusions:BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI, and its combination with HBO has a synergistic effect.
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Objective To investigate the effect of arterial and venous subarachnoid hemorrhage ( SAH)on voltage-dependent calcium channel( VDCC)currents of cerebral artery smooth muscle cells and the relationship between the concentration of oxyhemoglobin( OxyHb)in arterial and venous blood and cerebral blood flow. Methods Thirty-six clean grade rats were colleted. A rat SAH model was induced by injection of autologous arterial or venous blood in suprasellar cistern using assisted stereotaxic apparatus. The rats were divided into three groups:an arterial SAH( n=14 ),a venous SAH( n=13 ),and a sham operation( n=9 )group. The arterial and venous OxyHb concentrations were measured. Three days after SAH modeling,a patch clamp was used to detect the relative surface area of the cerebral artery smooth muscle cells,resting potential,and VDCC currents in rats. A fluorescent microsphere method was used to quantitatively analyze cerebral blood flow(CBF). Results (1)Arterial SAH OxyHb concentration (127 ± 4 g/L)was significantly higher than venous SAH OxyHb concentration(54 ± 6 g/L),and that of the sham operation group was 50 ± 5 g/L. The differences were statistically significant among the 3 groups( P<0. 01).(2)The maximum current of VDCC of the arterial SAH group(3. 22 ± 0. 31 pA)was significantly higher than that of the venous SAH group(2. 19 ± 0. 27 pA)and the sham operation group(2. 18 ± 0. 29 pA). The differences were statistically significant among the 3 groups( P<0. 01 ). The VDCC currents of the arterial SAH group were consisted of L- and R-currents,while the currents of the venous SAH group were only consisted of L-VDCC.(3)The cerebral blood flow of the arterial SAH group(0. 83 ± 0. 14 mL/[g·min])was significantly higher than that of the venous SAH group(1. 28 ± 0. 28 mL/[g·min])and the sham operation group(1. 35 ± 0. 19 mL/[g·min]). The differences were statistically significant(P<0. 01). Conclusions The changing effect of arterial SAH on the expression and function of the cerebral artery smooth muscle cells are greater than that of the venous SAH. This difference may be associated with the concentration and composition of vasospasm factors of OxyHb in arterial and venous blood.
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Objective To study the effect of subarachnoid hemorrhage (SAH) on voltagedependent potassium channels (Kv) currents of smooth muscle cells,which is hypothesized to be different between cerebral pial arteries and penetrating arteries.Methods Smooth muscle cells from cerebral pial arteries and penetrating arteries in rats were enzymatically isolated 72 h after SAH,and patch clamp was used to test the relative cell size,resting potential and Kv currents.Results Resting potential of either pial ((45.63 ±1.18) mV) or penetrating artery ((41.55-± 1.19) mV) was shifted positively by SAH,even more significantly in latter (F =8.24,P ＜ 0.05 ; F =9.36,P ＜ 0.01) ; Resting potential of pial artery of control ((38.76 ± 1.03) mV),penetrating artery of control ((38.53 ± 0.67) mV),pial artery of SAH ((36.87 ± 1.49) mV) and penetrating artery of SAH((37.89 ± 1.24) mV) were shifted positively to the same level by 1 μmol/L 4-aminopyridine (4AP; F =3.08,P ＞0.05).Maximum Current Density (Imax) of either pial ((20.82 ±0.59) pA/pF) or penetrating artery ((15.15 ±0.37) pA/pF) was compromised by SAH,also more significantly in latter (F =6.22,P ＜ 0.05) ; Imax of pial artery of control (9.15 ± 0.16),penetrating artery of control (9.04 ± 0.36),pial artery of SAH (8.77 ± 0.26) and penetrating artery of SAH (9.12 ± 0.17) were decreased to the same level by 1 μmol/L 4AP (F =2.96,P ＞ 0.05).Conclusions SAH probably shares the similar pathway with Kv blocker (4AP) in Kv currents inhibition.Further,SAH differently inhibits smooth muscle cells Kv currents and resting potential of cerebral pial arteries and penetrating arteries,which may be related with their different sensitivity towards cerebral vasospasm following SAH.
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Objective To investigate the clinical value of stereotactic biopsy in the diagnosis of the multiple intracranial lesions, and explore the operation methods, technical points and clinical experiences to reduce surgical complications. Methods Twenty-three patients in the first affiliated hospital of Kunming Medical University underwent stereotactic biopsy from January 2009 to June 2013 were analyzed retrospectively. The patients were aged between 11 and 73 years (the mean age of 34.6 years) . There were 12 males and 11 females. Operations were performed by thin thickness of spiral CT scan, ASA-602S and Leksell-Frame-G stereotactic frame, Sedan side-cutting needle, Backlund side-cutting needle and neuroendoscope of STORZ. Routine histopathological examinations of specimens were conducted. The immunohistochemical staining of the histopathological section of specimens was performed if necessary. Results The diagnostic yield was 91.3% (21 cases) . The result of pathological diagnosis was inflammatory granuloma in 1, inflammatory lesion in 1, calcification in 1, hyperplasia of colloid cells in 6, astrocytoma in 1 (WHOⅠ-Ⅱ), astrocytoma in 2 (WHOⅡ), astrocytoma in 1 (WHOⅡ-Ⅲ), mixed oligoastrocytoma in 1 (WHOⅠ-Ⅱ), glioblastoma multiforme in 3 (WHOⅣ), germinoma in 1, brain metastases in 1, diffuse large B-cell lymphoma in 1, intracranial granulomatousarteritis in 1 and negative in 2. There were no serious complications, such as coma, hemiparalysis, infection and intracranial hematoma. Conclusion Stereotactic biopsy is an important method in the diagnose of multiple intracranial lesions. It has the advantages of precise location, less damage, safe performance, and reducing the complication effectively. It is worth promoting.
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Objective To summary the experience of microsurgery of meningioma in skull base treatment. Methods To study the clinical data of 10 cases patients of meningioma in skull base who were subjected to microsurgery by using retrospective analysis. Among the 10 patients, there were 3 cases of meningioma of the olfactory groove. There were 2 cases of sphenoid ridge meningioma, meningioma in the middle cranial fossa, meningioma in the cerebellopontine angle respectively.There was 1 case of meningioma of velarium in temporal lobe. Results In 7 cases, the meningioma was completely removed. And in another 3 cases, the meningioma got subtotal resection. During and after the operation, there were no severe complications observed or death occurrence in all the 10 cases of meningioma patients. Two months post of operation,all patients got a significant amelioration in their symptoms. A total of 9 cases were followed up. There was 1 case of IIa type meningioma recurred. Conclusion To elevate the whole shearing rate of meningioma in skull base and reduce the mortality of it,it is most important for appropriate operative route selection and well mircosugical technique application.
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ObjectiveTo assess the recent effect of the invasiveness and transsphenoidal microsurgical operation in the treatment of growth hormone-secreting adenom tumor.MethodsThe data of 22 patients with growth hormone(GH) adenomas were collected.All patients were tested preoperative GH level and that within the first 3 days,30 days following surgery.The invasiveness of pituitary adenomas was judged according to Hardy's classification scheme modified by Wilson.ResultsThere were 22 patients with GH-secreting pituitary adenomas,8 males and 14 females,11 patients with invasive adenomas and 11 patients with noninvasive adenomas.The remission rate between the patients with invasive adenomas and the patients with non-invasive adenomas had no statistically significant difference (P ＞ 0.05 ).The postoperative remission rate of patients with GH values ≤ 50μg/L was no significantly lower than that of ＞ 50μg/L( P ＞ 0.05).ConclusionThe recent effects of operation were not significantly different with the invasiveness of tumor.
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Objective To observe the migration and distribution of OECs in injured spinal cord and discuss their relation with the recovery of spinal cord function. Methods The rats were contused by a force of 10 g · 25 mm with NYU-impactor at T10 level. The OECs acutely isolated from green fluorescence protein (GFP) rats were purified, identified and then transplanted into the injured site and the rostral and caudal parts of the spinal cord one week after injury, with total volume of the transplanted OECs for 90 000/μl. Within 13 weeks after transplantation, the migration and distribution of OECs were qualitatively observed on the cryo-sections under fluorescence light microscope. The area and the length of OECs distribution were semi-quantitatively determined. The locomotor function of the spinal cord was appraised by BBB score. Results OECs were located collectively in the transplanted site at early stage after transplantation and then spread gradually mainly along the long axis of the cord. OECs could be found in the cavity of the contused spinal cord. The area and the length of OECs distribution were increased from 1.33 mm2 and 4.23 mm respectively at one week to 3.30 mm2 and 7.68 mm respectively at 13 weeks after transplantation. In the meantime, the locomotor function was gradually improved. Conclusion OECs can migrate within the contused spinal cord, as may contribute to the recovery of locomotor function.
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Objective To summarize the experience of the trans-unilateral nasal and sphenoidal approach to pituitary denomas.Methods 20 cases of pituitary adenomas were removed by the trans-unilateral nasal and sphenoid approach under operating microscope,of which there were 2 microadenoma patients,16 macroadenoma patients;2 giant pituitary adenoma patients.Results Of all the 20 patients,12 had total resection of tumor;4 had subtotal resection of tumor and 4 had part resection of tumor.All cases showed improvement.After the operation,3 had diabetes insipidus and 2 had CSF rhinorrhea,which had been cured by the time they left the hospital.Conclusion this method is minimally invasive with short operative distance,time and fewer complications.