The PI3K/AKT cell signaling pathway is involved in regulation of osteoporosis.

BACKGROUND: Osteoporosis is a systemic skeletal disease with the high incidence, serious complications, financial burden, and heavily decrease in living quality. METHODS: Proliferation of osteoblast was tested by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, alkaline phosphatase (ALP) activity of osteoblasts was tested by ALP REAGENT, Calcium level was determined by a colorimetric assay, mRNA expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1 (PDK1), Akt, Caspase-3, Caspase-7, Caspase-9, osteocalcin (OCN), Osterix and Runx2 of osteoblasts was tested by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR), and protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt was measured by Western Blot analysis. RESULTS: In osteoporosis model rats, it found that mRNA expression of PI3K, PDK1 and Akt showed no changes while protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt in bone tissue was decreased dramatically. To further characterize the molecular mechanisms that regulate osteoporosis, we examined the contribution of the PI3K/Akt cell signaling pathway in cultured osteoblasts. It suggested that, the blockade of PI3K activation by LY294002, a specific inhibitor of the PI3K/Akt signaling pathway in osteoblasts, heavily inhibited cell proliferation, ALP activity, calcium accumulation, and mRNA expression of OCN, Osterix and Runx2. However, mRNA expression of Caspase-3 and Caspase-9 was promoted accordingly. CONCLUSION: The in vivo and in vitro studies indicated that the PI3K/Akt cell signaling pathway is involved in the inhibition of osteoporosis through promoting osteoblast proliferation, differentiation and bone formation.

[Effect of Shen warming Pi strengthening method on the expression of serum T cell subsets in IBS-D rats].

OBJECTIVE: To observe the effect of Shen warming Pi strengthening method on expressions of serum T cell subsets (C045+%, C03+%, and C04 +/COB+) in diarrhea-predominant irritable bowel syndrome (IBS-0) rats. Methods An IBS-0 rat model was established referring to AL-Chaer's modeling method combined with tail clamp and intragastric administration of sanna leaf. After modeling 30 SO rats were randomly divided into 6 groups according to random digit table, i.e., the model group, the high, middle, low dose Wenshen Jianpi Recipe (WJR) groups, and the Sishen Pill control group, 6 in each group. A normal control group consisting of 6 SO rats were also set up. Rats in high, middle, low dose WJ R groups were administered by gastrogavage with boil-free WJ R at the daily dose of 3. 100, 1. 550, 0. 775 g/kg, respectively. Rats in the Sis hen Pill control group were administered by gastrogavage with boil-free Sis hen Pill at the daily dose of 0. 736 g/kg. Equal volume of normal saline was given by gastrogavage to rats in the model group and the normal control group. All medication lasted for 2 successive weeks. Rats' general state, expressions of T cell subsets (CD45+%, CD3+%, and CD4+ /CDB+) changes were observed. RESULTS: Compared with the normal control group, expressions of CD45+% and CD3+% increased, but CD4+ /CDB+ decreased with statistical difference (P < 0. 05). Compared with the model group, expressions of CD45+% and CD3+% decreased, but CD4+ ICDB+ increased with statistical difference in high, middle, low dose WJR groups, and the Sis hen Pill control group (P <0. 05). Compared with the Sis hen Pill control group, there was statistical difference in all indices except CD45+ value in the low dose SWPSM group (P <0. 05). Compared with the low dose WJ R group, the expression of CD3+% decreased in high and middle dose WJR groups, and the Sis hen Pill control group; CD4+ /CD8+ increased in the Sishen Pill control group and the high dose SWPSM group (all P < 0. 05). CONCLUSIONS: WJR showed better treatment effect. The mechanism of Shen warming Pi strengthening method might be achieved by regulating expressions of CD45+% and CD3+%, and CD4+ /CD8+ ratios.

[Shen warming Pi strengthening method intervened IBS-D rats: an efficacy assessment].

OBJECTIVE: IBS-D rat model was established to assess the effect of Shen warming Pi strengthening method (SWPSM) for intervening diarrhea-predominant irritable bowel syndrome (IBS-D) by observing rats' general state, stool properties, AWR ranking, and histopathological changes. METHODS: Totally 72 rats were randomly divided into 6 groups, i.e. the normal group, the model group, the high, middle, low dose SWPSM groups, and the control group, 12 in each group. The IBS-D rat model was successfully established referring to AL-Chaer ED's modeling method. After modeling high, middle, and low dose SWPS Recipe boil-free granules were given by gastrogavage to rats in corresponding treatment groups. Sishen Pill boil-free granule was given by gastrogavage to those in the control group. Equal volume of normal saline was given by gastrogavage to rats in the model group. The medication lasted for 2 weeks. Rats' general state, stool properties, abdominal withdrawal reflex (AWR) ranking, and histopathological changes were observed. RESULTS: After treatment, the general state of all rats got im- provement to various degrees. The improvement in the high and middle dose SWPS Recipe groups were superior to that in the low dose SWPS Recipe group and the control group (P < 0.05). There was no statistical difference in the growth rate between after and before treatment in each group (P > 0.05). Compared with the model group and the low dose SWPS Recipe group, the defecation amount within 4 h was less in the high and middle dose SWPS Recipe groups and the control group (P < 0.05). The Bristol ranking score, average ranking of loose stool, ratio of dry stool and wet stool were lower in the high and middle dose SWPS Recipe groups than in the control group and the low dose SWPS Recipe group (P < 0.05). The AWR ranking score was lower in the high and middle dose SWPS Recipe groups than in the control group when the volume of balloon dilation was 1.5 mL. There was no organic change of histological or morphological observation. CONCLUSIONS: High sensitive IBS-D model was proved to be reliable. SWPSM could reduce the quantity of stools, lower Bristol ranking score, average ranking of loose stools as well as ratios of dry stool and wet stool, contributing to reducing the high sensitivity of rats' visceral organs to some extent.

Outcomes of different surgical procedures in the treatment of spinal tuberculosis in adults.

OBJECTIVE: To investigate surgical methods and outcomes in the treatment of spinal tuberculosis (TB) in adults. SUBJECTS AND METHODS: One hundred and eighty-one patients (average age 39 years) without multiple-level noncontiguous spinal TB were followed up for 22-72 months. The patients were divided into four groups according to surgical procedure on the basis of the position and extension of the foci: group A (74 cases): anterior radical debridement and strut grafting with instrumentation; group B (83 cases): posterior instrumentation and bone grafting with anterior radical debridement and strut grafting in a single- or two-stage procedure; group C (10 cases): extrapleural anterolateral decompression and strut grafting with posterior instrumentation in thoracic or thoracolumbar spine, and group D (27 cases): single-stage transforaminal decompression and posterior instrumentation and fusion. RESULTS: There was a significant decrease (p < 0.05) in mean preoperative (81%) Oswestry's Disability Index. Except for 24 patients with lumbosacral TB who were only instrumented posteriorly, kyphosis degrees were corrected by a mean of 11.5° in the anterior instrumentation group and 12.6° in the posterior instrumentation group (p < 0.01). The correction loss was 6.8° in the anterior instrumentation group and 6.1° in the posterior instrumentation group at the last follow-up (p < 0.01). CONCLUSION: The four surgical procedures obtained good results for correction and maintenance of the correction, clearance of the foci, decompression of the spinal cord and pain relief in the treatment of spinal TB in adults, providing that the operative indication is accurately identified. However, the posterior approach was superior to anterior instrumentation for correcting deformity and maintaining the correction.

Outcomes of anterior and posterior instrumentation under different surgical procedures for treating thoracic and lumbar spinal tuberculosis in adults.

PURPOSE: There are few articles in the literature comparing outcomes between anterior and posterior instrumentation in the management of thoracic and lumbar spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 217 adult patients, average age 39 (range 16-67) years with thoracic and lumbar spinal TB were treated by anterior radical debridement and fusion plus instrumentation, anterior radical debridement with fusion and posterior fusion with instrumentation, posterolateral debridement and fusion plus posterior instrumentation or transpedicular debridement and posterior fusion with instrumentation in a single- or two-stage procedure. We followed up 165 patients for 22-72 (mean 37) months. Of these, 138 underwent more than three weeks chemotherapy with isoniazid, rifampin, pyrazinamide and ethambutol, and the remaining 27 underwent operation for neurological impairment within six to 18 hours of the same chemotherapy regimen. In no case did relapse occur. Apart from eight patients with skip lesions treated by hybrid anterior and posterior instrumentation, anterior instrumentation was used in 74 patients (group A) and 83 patients (group B) were fixed posteriorly. RESULTS: In both groups, local symptoms were relieved significantly one to three weeks postoperatively; ten of 14 patients (71%) in group A and 14 of 19 (74%) in group B with neurological deficit had excellent or good clinical results (P > 0.05). Erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.7 mm/h, respectively, preoperatively to normal levels eight to 12 weeks postoperatively. Kyphosis degree was corrected by a mean of 11.5° in group A and 12.6° in group B, respectively (P < 0.01). Correction loss was 6.8° in group A and 6.1° in group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were 92.5% and 91.8%, respectively, at final follow-up (P > 0.05). Severe complications did not occur. CONCLUSION: These results suggest that both anterior and posterior instrumentation attain good results for correction of the deformity and maintaining correction, foci clearance, spinal-cord decompression and pain relief in the treatment of thoracic and lumbar spinal TB providing that the operative indication is accurately identified. However, the posterior approach may be superior to anterior instrumentation to correct deformity and maintain that correction.

[Diagnosis and treatment of lumbar disc herniation by discography and percutaneous transforaminal endoscopic surgery].

OBJECTIVE: To conduct a retrospective analysis of diagnosis and treatment of lumbar disc herniation by discography and percutaneous transforaminal endoscopic surgery. METHODS: From December 2009 to June 2010, 119 patients with lumbar disc herniation underwent discography and transforaminal endoscopic surgery under local anesthesia. There were 75 males and 44 females with a mean age of 44.8 years (range: 15 - 55). The mean disease course was 9 months (range: 3 - 72). The major symptoms were back pain and/or unilateral sciatica. The mean follow-up period was 26 months. All underwent lumbar radiography, computed tomography (CT) and magnetic resonance imaging (MRI) revealing 112 single level and 7 two-level disc herniations. There were 82 lateral and 37 para-medial disc herniations. Eight-nine patients had protruded discs while 30 had prolapsed and sequestered discs. There were no obvious lumbar stenosis, spondylolisthesis, fracture, infection or tumor cases. The preoperative and postoperative visual analogue scale (VAS) were used to evaluate the sciatica and/or back pain. The outcomes were evaluated by Oswestry disability index (ODI) and the Macnab score. Precise orientation and operation was performed under the guidance of pre-operative imaging, intra-operative fluoroscopy or CT and endoscopic exploration. RESULTS: Among them, 117 cases had the surgery performed successfully. The mean operative duration was 85 min (range: 35 - 85) and the mean blood loss 13 ml (range: 1 - 50). One patient had L5 nerve root injury complicated with paraesthesia and weakness of the affected lower extremity and was relieved gradually after conservative treatment for over 3 months. Another one complicated with postoperative intradiscal infection was referred to another institution and lost follow-up thereafter. Five cases had no improvement at 6 months after the first surgery and were re-operated endoscopically. No one had a conversion into open surgery. They were followed up for a mean period of 26.1 months (range: 25 - 27). Five patients lost follow-up. VAS improved statistically significantly from preoperative 6.8 to postoperative 1.8 (P < 0.05). ODI decreased from preoperative 70.06 to 19.09 at the last follow-up. The Macnab results were excellent (n = 82, 68.9%), good (n = 20, 16.7%), fair (n = 8, 6.7%) and bad (n = 9, 7.7%) (including all patients lost to follow-up). And the excellent-to-good rate was 85.6%. CONCLUSION: With fewer complications and a low recurrence rate, percutaneous transforaminal endoscopic surgery is safe and efficacious in the treatment of lumbar disc herniation.

[Outcomes of anterior versus posterior instrumentation under different surgical procedures in the treatment of thoracolumbar spinal tuberculosis in adults].

OBJECTIVE: To compare the outcomes of anterior verus posterior instrumentation under different surgical procedures in the surgical management of thoracolumbar spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 241 adult patients with thoracolumbar spinal TB underwent radical debridement and strut grafting plus anterior or posterior instrumentation in single-stage or two-stages. The mean age was 39 years (range: 16 - 67). The mean follow-up period for 189 patients was 37 months (range: 22 - 72). Among them, 157 cases underwent > 3 weeks of chemotherapeutic regimen of isoniazid, rifampin, pyrazinamide and ethambutol and the remaining 32 were operated for neurological impairment after 6-18 h with the same chemotherapeutic regimen. Except for 8 patients with skip lesions undergoing hybrid anteroposterior instrumentation, anterior instrumentation was utilized in 74 patients (Group A) and posterior instrumentation in 107 patients (Group B). RESULTS: In both groups, local symptoms of all patients were relieved significantly 1-3 weeks postoperatively. And 10/14 cases (71%) in Group A and 14/19 cases (74%) in Group B with neurological deficits had excellent or good clinical outcomes (P > 0.05). The levels of erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.4 mm/h preoperatively to normal at 8-12 weeks postoperatively. Kyphosis degrees were corrected by a mean of 11.5° in Group A and 12.6° in Group B (P < 0.01). The correction loss was 6.8° in Group A and 6.1° in Group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were 92.5% and 91.8% respectively at the final follow-up (P > 0.05). Severe complications did not occur. CONCLUSION: Either anterior or posterior instrumentation can obtain good results in correction and maintenance of deformity, clearance of foci, decompression of spinal cord and pain relief in the treatment of thoracolumbar spinal TB as long as the surgical indications are properly selected. Posterior instrumentation may be superior to anterior instrumentation in the correction and maintenance of deformity.

Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer.

PURPOSE: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. MATERIALS AND METHODS: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. RESULTS: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. CONCLUSION: The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Wnt4 is significantly upregulated during the early phases of cisplatin-induced acute kidney injury.

Wnt4 is a secreted growth factor associated with renal tubulogenesis. Our previous studies identified that renal and urinary Wnt4 are upregulated following ischemia-reperfusion injury in mice, but the roles of Wnt4 in other forms of acute kidney injury (AKI) remain unclear. Here, we investigated the changes in Wnt4 expression using a cisplatin-induced AKI model. We found that renal and urinary Wnt4 expression increased as early as 12 hours, peaked at day 4 following cisplatin-induced AKI and was closely correlated with histopathological alterations. By contrast, the serum creatinine level was significantly elevated until day 3, indicating that Wnt4 is more sensitive to early tubular injury than serum creatinine. In addition, renal Wnt4 was co-stained with aquaporin-1 and thiazide-sensitive NaCl cotransporter, suggesting that Wnt4 can detect both proximal and distal tubular injuries. These data were further confirmed in a clinical study. Increased urinary Wnt4 expression was detected earlier than serum creatinine and eGFR in patients with contrast-induced AKI after vascular intervention. This study is the first to demonstrate that increased expression of renal and urinary Wnt4 can be detected earlier than serum creatinine after drug-induced AKI. In particular, urinary Wnt4 can potentially serve as a noninvasive biomarker for monitoring patients with tubular injury.

[Is allograft a procedure with high-risk in anterior cervical fusion].

OBJECTIVE: The anterior cervical autograft or allograft interbody fusion had become an accepted fusion technique for treating patients with degenerative disorders of the cervical spine. In this retrospective review, a comparison of allograft and autograft of bone was presented. METHODS: A retrospective review of 103 patients who had undergone allograft fusion and 145 patients with autograft fusion between 1997 and 2003, was conducted. Demographics, early complications and length of stay of patient were compared. RESULTS: Longer time on operation with the use of autograft (P < 0.001) and significant increase in length of stay were observed after autograft (P < 0.001). Complication of infections in autograft group was higher than allograft (P < 0.05). CONCLUSIONS: Both autograft and allograft were effective during fusion procedures. Allograft did not appear to be a high risk factor and could decrease medical cost thus could be used clinically for anterior cervical fusion.