C5aR antagonist inhibits occurrence and progression of complement C5a induced inflammatory response of microglial cells through activating p38MAPK and ERK1/2 signaling pathway.

OBJECTIVE: To discuss the effect of complement C52 (C5a) and complement C5a receptor (C5aR) antagonists on inflammatory status of mouse microglial cells. MATERIALS AND METHODS: Primary culture was performed on mouse microglial cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect effect of C5a and C5aR antagonists on vitality of microglial cells. The effect of C5a and C5aR antagonists on mRNA expression of p38MAPK and ERK1/2 was determined using quantitative PCR (qPCR). Enzyme linked immunosorbent assay (ELISA) was used to measure expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cells. RESULTS: According to quantitative fluorescent PCR, relative expression of p38MAPK and ERK1/2 mRNA in C5a antagonist treatment group was significantly higher compared to normal group and C5a+C5aR antagonist treatment group (p<0.05). However, the relative expression of the C5a+C5aR antagonist treatment group was significantly lower compared to that of the normal group (p<0.05). Expression of Iba1, p-p38MAPK and p-ERK1/2 proteins in C5a antagonist treatment group was significantly higher than normal group, in C5a+C5aR antagonist treatment group was lower than C5a antagonist treatment group (p<0.05). There were significant differences for IL-6 and TNF-α levels among 5 groups (p<0.05). Expression of cytokines was the highest in 100 nM C5a antagonist treatments and lowest in normal group. CONCLUSIONS: Complement C5a upregulated expression of inflammatory factors in mouse microglial cells, while C5aR antagonist inhibited occurrence and progression of inflammatory status. This was achieved by affecting transcriptional and translational processes of different factors in p38MAPK and ERK1/2 signaling pathway.

[Effect of different course of omeprazole in the treatment of laryngopharyngeal reflux].

Objective:To compare the efficacy and safety of omeprazole in the treatment of laryngopharyngeal reflux. Method:One hundred and sixty patients with laryngopharyngeal reflux in our hospital from March 2015 to January 2017 (diagnosis treatment for 8 weeks) were selected and randomly divided into group A, B, C, D, with 40 cases in each group. Each group of patients were treated with omeprazole enteric-coated capsules (20mg, Bid) for 1, 2, 3 and 4 months, respectively. The reflux symptom index(RSI), reflux finding score(RFS) score, and 24h intraesophageal pH-metry , pepsin detection were compared between the four groups before treatment, at the end of treatment, at 1 month and 2 months after treatment. The efficacy and side effects were evaluated.Result:With the increase of treatment course, patient's RSI and RFS score, 24h pH-metry <4.0 percentage, pepsin positive rate decreased gradually, and there was a significant difference between before and after treatment. After treatment, there was a statistical significance in group B and group A, group C and group B. There was no significant difference between group D and group C. After the end of treatment and up to 2 months of follow-up, the RSI and RFS scores gradually increased and 24h Ph-metry <4.0 percentage, pepsin positive rate increased in group A and B,and those were not significantly different in group C and group D. With the increase of treatment duration, the effective rate of treatment increased, which was 67.5%, 80.0%, 90.0% and 95.0%, respectively. The difference was statistically significant, but the adverse effects did not increase (P>0.05).Conclusion:Omeprazole is safe and effective in the treatment of laryngopharyngeal reflux. The symptoms and signs of the patients are obviously improved during the 5 months of the course, and the condition is relatively stable and the recurrence rate is low.

[Anterior cervical discectomy and fusion to treat cervical spondylosis with sympathetic symptoms].

OBJECTIVE: To investigate the clinical effectiveness of polytheretherketone (PEEK) cages assisted anterior cervical discetomy and fusion (ACDF) to treat cervical spondylosis with sympathetic symptoms. METHODS: Retrospective analysis was undertaken for 39 patients who were diagnosed as cervical spondylosis with sympathetic symptoms and underwent ACDF with PEEK cages. Radiographs obtained before surgery, after surgery, and at the final follow-up were assessed for quality of fusion. The following criteria were used for assessing radiographic success of fusion: (1) endplate obliterated with no lucent lines; (2) obliteration of disc space by bony trabeculae; (3) less than 2°of intervertebral motion or 2 mm of motion between the spinous processes at the operated segment on flexion-extension lateral radiographs. The sympathetic symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb, hypomnesia and gastroenterological discomfort were scored by 20-point system preoperatively, 2 months postoperatively and at the final follow-up. The recovery rate and clinical satisfaction rate were also evaluated. Surgical complications were also assessed. RESULTS: They were followed up for at least one year. The mean follow-up was 15.6 months. Radiographs of the cervical spine at the last follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases. In two patients delayed union and bony fusion were achieved at the end of 9 and 11 months. Pseudoarthosis was found in 1 case but the patient had no symptoms. The score of sympathetic symptoms before surgery, 2 months after surgery and at the final follow-up were 8.4±1.0,2.2±0.3,and 2.4±0.3, respectively. There were 22 excellent cases, 15 good cases, 1 fair case and 1 bad case in terms of RR. Good to excellent results were attained in 95% of theses patients. The sympathetic symptoms improved in all the patients and the score was significantly improved after surgery. There was one patient who had cerebral spinal fluid leakage but he recovered one week after surgery. Two patients felt a mild swallowing discomfort, but it disappeared within one month after surgery. Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was cleared two days after surgery. CONCLUSION: Cervical spondylosis patients with sympathetic symptoms may be managed successfully with ACDF using PEEK cages. Successful clinical results regarding symptom improvement and general satisfaction with the surgical procedure depend not only on obtaining successful decompression and radiographic fusion but also on patient selection.

Ablation of Tacr2 in mice leads to gastric emptying disturbance.

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.

[Polymethylmethacrylate augmentation of bone cement injectable cannulated pedicle screws was used to treat degenerative lumbar scoliosis with osteoporosis].

OBJECTIVE: To describe the application of polymethylmethacrylate (PMMA) augmentation of cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis. METHODS: Retrospective cohort study was used to compare cement injectable cannulated pedicle screws (CICPs) group with PMMA augmentation and control group with traditional method in the correction surgery for Lenke-silva level III and level IV degenerative scoliosis cases with osteoporosis. Both groups were followed up for 1 year. The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers, Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D) score. The coronal major curve Cobb angel in coronal plane and thoracic kyphosis Cobb angle, lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in sagittal plane were tested in whole long spine X ray. The fusion rates were evaluated by lumbar X ray and dynamic X ray. RESULTS: In this study 34 cases were enrolled, 15 cases in CICPs group and 19 cases in control group. The general characteristics including age, gender, weight, height, BMI and BMD were without statistical difference between the two groups. There were (5.7±2.2)PMMA augmentation screws in CICPs group. The operation time, blood loss and blood transfusion were higher in CICPs group than in control group, but without statistical difference. Lumbar VAS, lower limbers VAS, ODI score and EQ-5D were all better in 1 month postoperation, 6 months postoperation and 1 year postoperation than in preoperation in both groups. lumbar VAS scores of CICPs group in 6 months postoperation (CICPs group 3.1±1.3 vs. control group 4.4±1.4, P<0.01) together with lumbar VAS scores (CICPs group 3.3±1.0 vs. control group 5.2±1.4, P<0.01), ODI scores (CICPs group 22.7±17.2 vs. control group 31.4±18.5, P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9±2.0 vs. control group 3.5±2.5, P<0.01)were lower than those of control group. The coronal major curve Cobb angels were all lower in 1 month postoperation, 6 months postoperation and 1 year postoperation than in preoperation in both groups; thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1 month postoperation, 6 months postoperation and 1 year postoperation than in preoperation in both groups. The coronal major curve Cobb angel was lower in CICPs group than that in control group in 1 year postoperation (CICPs group 17.6°±6.9° vs. control group 21.2°±7.2°, P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in control group in 6 months postoperation (CICPs group -33.5°±8.8 ° vs. control group -28.9°±8.3°, P<0.01) and 1 year postoperation (CICPs group -33.0°±8.1° vs. control group -26.3°±7.4°, P<0.01) together with lumbar lordosis Cobb angle were higher in CICPs group than that in control group in 1 year postoperation (CICPs group 26.4°±8.1° vs. control group 22.1°±7.3°, P<0.01). CONCLUSION: Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar scoliosis with osteoporosis was effective and safe, the short-term clinical result was good.

[Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar diseases with osteoporosis].

OBJECTIVE: To describe the application of polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar diseases with osteoporosis. METHODS: Observation group included 14 cases of degenerative lumbar diseases with osteoporosis received polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws from November 2014 to July 2015, control group included 12 cases of degenerative lumbar diseases with osteoporosis received polymethylmethacrylate augmentation with traditional pedicle screws.The operation time, blood loss, number of pedicle screws and number of augmented pedicle screws in the two groups were compared. The bone cement leakage and pulmonary bone cement embolism in the two groups were also compared. The fusion rate and pedicle screws loosening by lumbar X ray and dynamic X ray were evaluated. The clinical results were assessed by visual analog scale (VAS) of pain on lumbar and lower limbers, lumbar Japanese Orthopaedic Association scores (JOA), Prolo functional scores and Oswestry disability (ODI) scores. RESULTS: Differences of operation time and blood loss in the two groups were not statistically significant. The average number of pedicle screws was 9.9±4.7 and the average number of augmented pedicle screws was 5.9±2.6 in observation group while the average number of pedicle screws was 7.1±2.8 and the average number of augmented pedicle screws was 3.0±1.9 in control group. The ratio of augmented pedicle screws was higher in observation group than in control group (0.69±0.30 vs.0.47±0.30,P<0.05). The bone cement leakage rate was lower in observation group than in control group (5/83 vs. 12/42, P<0.01). All the cases in observation group were without leakage to the interspinal canal while one case in control group suffered from bone cement leakage to the interspinal canal with augmentation of 3 pedicle screws. The follow up period was (10.6±2.3) months in observation group and (36.5±7.2) months in control group. In final follow up, no case with non-fusion or pedicle screws loosening was found in both groups. Lumbar VAS, lower limbers VAS, lumbar JOA scores, Prolo functional scores and ODI scores were all better than pre-operation (P<0.01). CONCLUSION: Polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws for the treatment of degenerative lumbar diseases with osteoporosis was effective, with simple working processes and lower risk of bone cement leakage. The short-term clinical result was good.

[Analysis of the clinical outcomes of the over 5-year follow-up study of degenerative lumbar scoliosis treated with posterior decompression and instrumented fusion].

OBJECTIVE: To evaluate the over 5-year follow-up clinical outcomes of degenerative lumbar scoliosis treated with operation of decompression and fusion, and the effectiveness and risks factors about revision surgery cases. METHODS: A total of 47 cases of diagnosis of degenerative lumbar scoliosis treated with posterior decompression and instrument fusion recorded from Jun. 2003 to Jun. 2008 were analyzed. Lumbar Japanese Orthopedic Association (JOA) score and visual analogue score (VAS) were applied to evaluate the improvement of the clinical effect after surgery treatment, and the clinical effect and reasons of revising operation were recorded and analyzed. RESULTS: All the 47 patients had finished the over 5-year followed-up time with an average time of (8.2±3.6) years (range from 5.2 years to 12.5 years). The patient's mean age was (67.0±9.6) years and the age of patient range from 56 years to 81 years. There were 10 patients who underwent revision surgery since primary operation, in whom 8 cases because of proximal failure of internal fixation and the other 2 cases because of distal failure of fusion segment. The average clinical improvement excellent rate was 83.3% after 5 years since primary operation of 37 cases while the average fine rate of revision operation was 67.6%. CONCLUSION: In the over 5-year follow-up, there was a better clinical outcome of degenerative lumbar scoliosis treated with posterior decompression and instrumented fusion, which had a certain rate of revision operation and had a worse effect of clinical results compared with primary operation. The risks of revision surgery included the poor bone quality of patients, with fusion to L1 at proximal terminal and the fusion end to S1 at distal terminal.

Up-regulation of the Ang II/AT1 receptor may compensate for the loss of gastric antrum ICC via the PI3k/Akt signaling pathway in STZ-induced diabetic mice.

The classic renin-angiotensin system (RAS) is a complex system in which angiotensin II (Ang II) has been identified as an important endogenous regulator that influences both smooth muscle contraction and cell growth. Although a local RAS is known to exist in the gastrointestinal tract, it is unclear whether Ang II is involved in the loss of gastric interstitial cells of Cajal (ICC) in diabetic mice. The present study was designed to investigate the effect of Ang II on ICC survival in streptozotocin (STZ)-induced diabetic mice. Western blot, immunofluorescence, isometric muscle recording, enzyme-linked immunosorbent assay (ELISA) and a cell counting kit-8 were used in this research. Our results demonstrate that the c-Kit and membrane-bound stem cell factor (mSCF) protein expression levels in gastric smooth muscle were decreased in STZ-induced diabetic mice. However, the angiotensin receptor type 1 (AT1R) expression levels in gastric smooth muscle and angiotensin-converting enzyme (ACE) expression levels in gastric mucosa were increased. The effect of Ang II on the tonic contraction of gastric smooth muscle was potentiated in diabetic mice, and the plasma Ang II level was enhanced. Ang II increased mSCF expression, cell proliferation, and Akt-Ser473 phosphorylation in cultured gastric smooth muscle cells (GSMCs). These effects were reduced by specific inhibitors ZD7155 (an AT1R antagonist) and LY294002 (a PI3-kinase inhibitor). Our results suggest that Ang II increases mSCF expression and cell proliferation in cultured GSMCs in a PI3K/Akt signaling-dependent manner. ACE and AT1R up-regulation in the stomach may help compensate for ICC loss in STZ-induced diabetic mice.

[The clinical significance of PRL-3,VEGF expression in sinonasalsquamous cell carcinoma].

Objective:To analyze the clinical significance of phosphatase of regenerating liver-3(PRL-3) and vascular endothelial growth factor(VEGF)expression in sinonasal squamous cell carcinomas.Method:We use immunohistochemical analysis and RT-PCR to detecte the expression of PRL-3 and VEGF protein in 62 cases of sinonasal squamous carcinoma tissues(SNSCC),30 cases of nasal polyps(NP),and 25 cases of normal nasal mucosa(NM).Result:①The expression of PRL-3 and VEGF in sinonasal squamous cell carcinoma tissues were statistically higher than in nasal polyps and normal nasal mucosa tissues (P<0.05).②The expression of PRL-3 and VEGF were not correlated with patient's age or gender(P>0.05).But the High expression of PRL-3 and VEGF in SNSCC was significantly related with advanced,lower tumor differentiation and lymph node metastasis(P<0.05).③The expression of PRL-3 and VEGF was positively correlated in sinonasal squamous cell carcinomas.Conclusion:The expression of PRL-3 and VEGF in SNSCC may involve in the regulation of tumor growth and differentiation.The expressing intensity may reflect the proliferation activity of sinonasal squamous cell carcinoma cell.PRL-3 and VEGF may promote the tumor metastasis in a synergistic manner.

[Clinical research of percutaneous vertebroplasty or percutaneous kyphoplasty for treating osteoporotic vertebral compression fractures induced by glucocorticosteroid].

OBJECTIVE: To investigate the clinical characteristics of vertebral compression fracture (VCF) in glucocorticosteroid-induced osteoporosis (GIOP) and risk of vertebral refracture after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP). METHODS: In the study, 570 cases who received PVP or PKP as treatments of VCF from January 2010 to December 2013 were retrospective reviewed, of which 42 were GIOP and 21 were followed up as GIOP group, and the other 528 were primary osteoporosis and 391 were followed up, of which 84 were selected as Control group based on age and gender. The fracture location, ratio of single segment fracture and multiple segments fracture in the two groups were compared. In the final follow up, the reoperation rates for vertebral refractures by the Kaplan-Meier method in the two groups were compared. RESULTS: The follow up periods were (24.0± 13.1) months in GIOP group and (25.8±14.4) months in control group(P>0.05). In GIOP group, there were 11 cases with one-segment fracture, 2 with two-segments fracture, 3 with three-segments fracture, 2 with four-segments fracture, 2 with five-segments fracture and 1 with eight-segments fracture. In Control group, there were 67 cases with one-segment fracture, 12 with two-segments fracture, 3 with three-segment fracture, and 2 with four-segments fracture. The ratio of single segment fracture in GIOP group was significantly lower than that in Control group(52.4% vs. 79.8%,P=0.01). There were 50 fracture segments in GIOP group and 109 fracture segments in Control group. The ratios of fracture segments located in thoracic segments(T1-T10), thoracolumbar segments(T11-L1)and lumbar segments(L2-L5)were 18%, 46% and 36% in GIOP group and 11.9%, 58.7% and 29.4% in Control group (P>0.05). The refracture rate in GIOP group was higher than that in control group (23.8% vs. 6.0%). The survival rate was lower in GIOP group than that in control group (P<0.01). CONCLUSION: The predilection site of VCF was similar in GIOP and primary osteoporosis (thoracolumbar segments> thoracic segments> lumbar segments). The risk of multiple segments VCF was higher in GIOP than in primary osteoporosis. The risk of vertebral refractures after PVP or PKP was higher in GIOP than in primary osteoporosis.

Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.

Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.