[Expert consensus for Jingtong Granules in treatment of cervical radiculopathy in clinical application].

With the effects of activating blood and resolving stasis, and moving Qi to relieve pain, Jingtong Granules is widely used in the treatment of cervical radiculopathy in China. Long-term clinical application and related evidence have shown that the prescription has ideal effect in alleviating the pain in neck, shoulder, and upper limbs, stiffness or scurrying numbness, and scurrying pain caused by this disease. However, there is a lack of consensus on the clinical application of Jingtong Granules. Therefore, clinical first-line experts and methodology experts from all over the country were invited to compile this expert consensus. This expert consensus is expected to guide clinicians to use Jingtong Granules in a standardized and reasonable way, improve clinical efficacy, reduce medication risks, and benefit patients. First, according to the clinical experience of experts and the standard development procedures, the indications, syndrome characteristics, clinical advantages, and possible adverse reactions of Jingtong Granules were summarized. Then, through face-to-face interview of clinical doctors in traditional Chinese medicine and western medicine and survey of the clinical application, the clinical problems were summed up, and the consensus was reached with the nominal group method to form the final clinical problems. Third, evidence retrieval was carried out for the clinical problems, and relevant evidence was evaluated. The GRADE system was employed to rate the quality of evidence. Fourth, 5 recommendation items and 3 consensuses items were summarized with the nominal group method. Opinions and peer reviews on the consensus content were solicited through expert meetings and letter reviews. The final consensus includes the summary of evidence on the clinical indications, effectiveness, and safety of Jingtong Granules, which can serve as a reference for clinicians in hospitals and primary health institutions.

Soluble Klotho-integrin ß1/ERK1/2 pathway ameliorates myocardial fibrosis in diabetic cardiomyopathy.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Clinical application of the C2 pars screw technique in the treatment of ossification of the posterior longitudinal ligament.

BACKGROUND: Our research was designed to decide whether the application of C2 pars screws is an alternative choice for patients with OPLL involving the C2 segment. METHODS: A total of 40 patients who underwent cervical laminectomy with fusion (LF) from C2 to C6 for OPLL were reviewed. Among them, C2 pedicle screws were placed in 23 patients, who were the pedicle group, and C2 pars screws were placed in 17 patients, who were the pars group. The screw placement and vertebral artery (VA) anatomy presented by standard CT. General clinical characteristics and health-related outcomes were evaluated and compared preoperatively and during the follow-up period. RESULTS: The Pars group tended to have a shorter operation duration and less blood loss than the pedicle group (operation time: 115.29 ± 28.75 vs 133.48 ± 26.22, p = 0.044; blood loss: 383.53 ± 116.19 vs 457.83 ± 145.45, p = 0.039). Operation time and blood loss were both independently related to the pars group (operation time: OR = 0.966, p = 0.021; blood loss: OR = 0.993, p = 0.046). The idealization and acceptability of C2 screws in the pars group exceeded those in the pedicle group (100% vs 91.3%). However, no statistically obvious variation in the included complications or health-related outcomes between the pedicle and pars groups was observed. CONCLUSION: In the treatment of patients with OPLL involving the C2 segment, the application of C2 pars screws is an alternative choice, which is not only safer but also reduces the amount of blood loss, shortens the operation time and obtains a more ideal screw placement.

Erratum: 17ß-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway.

The authors asked for the change of the figure 1. They wanted to send the figure that was 200 times bigger under the microscope as described in Figure 1 caption, however, they mistakenly uploaded the wrong picture. Reference: 1. Tao Wang, Si-Dong Yang, Sen Liu, Hui Wang, Huan Liu, Wen Yuan Ding: 17ß-Estradiol Inhibites Tumor Necrosis Factor-alpha Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway. Med Sci Monit, 2016; 22: 4312-4322. DOI: 10.12659/MSM.900310.

Clinical effect analysis of laminectomy alone and laminectomy with instrumentation in the treatment of TOLF.

BACKGROUND: To explore the clinical effect of laminectomy alone and laminectomy with instrumentation in the treatment of TOLF. METHODS: A retrospective study was conducted on the clinical data of 142 patients with TOLF and laminectomy who underwent spine surgery at XXX Medical University from January 2003 to January 2018. According to whether the laminectomy was combined with instrumentation, the patients were divided into two groups: group A (laminectomy alone (LA), n = 77) and group B (laminectomy with instrumentation (LI), n = 65). Comparisons of possible influencing factors of demographic variables and operation-related variables were carried out between the two groups. In this study, the clinical effects of LA and LI in the treatment of TOLF were discussed. Thus, we explored the clinical effect of LA and LI in the treatment of TOLF. RESULTS: In terms of demographics, there was a statistically significant difference in BMI between group A and group B (P < 0.05). The differences in age, sex, smoking, drinking, heart disease, hypertension and diabetes were not statistically significant (P > 0.05). In terms of preoperative symptoms, there was a significant difference in gait disturbance, pain in the LE, and urination disorder between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). In terms of operation-related variables, there was a significant difference in the preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT, shape on the sagittal MRI, operation time, pre-mJOA, post-mJOA at 1 year, and leakage of cerebrospinal fluid between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). The preoperative average JOA score of group A was 6.37 and that of group B was 5.19. In group A, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.87, 8.23 and 8.26, respectively, and the average JOA score improvement rate was 32.79 %, 38.32 and 38.53 %, respectively. In group B, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.74, 8.15 and 8.29, respectively, and the average JOA score improvement rate was 39.15 %, 46.86 and 47.12 %, respectively. CONCLUSIONS: Currently, there is no consensus on whether instrumentation is needed after laminectomy for TOLF. We found that for patients with a long duration of gait disturbance, urination disorder, preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT less than 60 %, and shape on the sagittal MRI being beak and low, pre-mJOA had better clinical effects after LI as compared to those after LA, and the incidence of perioperative complications was lower.

Does cervical facet degeneration impact surgical outcomes and sagittal balance in patients with radiculopathy?

PURPOSE: In our present study, we aimed to investigate (1) whether cervical facet degeneration (FD) affects the clinical functional scores of patients with cervical radiculopathy after single-segment anterior cervical discectomy fusion (ACDF) and (2) whether FD affects the sagittal parameters of the cervical spine. METHODS: A total of 120 enrolled patients who underwent single-segment ACDF for radiculopathy with more than 2 years of follow-up were classified into two groups based on whether the preoperative mean FD was greater than or less than the mean FD grading score: mild FD group (mean score ≤ 2, n = 102) or severe FD group (mean score > 2, n = 48). Sagittal alignment changes and clinical functional scores were compared between the 2 groups. The relevant factors for FD were identified using multivariate logistic regression. RESULTS: Age, duration of symptoms, disc height and interfacet distance were independently associated with preoperative FD (age: P < 0.001; duration of symptoms: P = 0.020; disc height: P < 0.001; interfacet distance: P = 0.045). Compared with the mild FD group, the preoperative VAS (neck pain) score and NDI of the severe FD group were also higher, and the improvement of neck symptoms was better during the follow-up period. However, all clinical scores and radiographic parameters showed no significant differences during the 2-year follow-up. Additionally, no significant differences in the sagittal parameter changes were presented. CONCLUSION: Patients with severe FD tended to experience more severe neck pain before surgery and greater improvement of neck symptoms at the follow-up visit. However, 2-year clinical efficacy and sagittal alignment after ACDF may not be markedly affected by preoperative FD severity. ACDF is considered to be a good choice for patients with radiculopathy, especially for patients with severe FD.

Spino cranial angle as a predictor of loss of cervical lordosis after laminoplasty in patients with cervical myelopathy.

BACKGROUND: To explore the relationship between spino cranial angle (SCA) and loss of cervical lordosis (LOCL), and to determine whether SCA has the ability to predict LOCL for patients with cervical myelopathy. METHODS: A total of 68 consecutive patients with cervical myelopathy who received laminoplasty (LAMP) were selected to the current study. C2-C7 lordosis was defined as a representation of the cervical alignment. Alignment change > 0° was considered LOCL. Multiple linear regression analysis was applied to evaluate the association between LOCL and various sagittal parameters at preoperative, such as SCA, CL, T1s and cSVA. Linear regression analysis was applied to evaluate the relationships between LOCL and preoperative SCA in each subgroup. RESULTS: Patients were assigned to three groups depending on the quartile of preoperative SCA. The first quarter of patients were defined as the low SCA group, the last quarter were defined as the high SCA group and the middle half were defined as the middle SCA group. There was no statistically significant difference in age, sex and the type of OPLL among the three groups. Patients in the low SCA group showed more cervical lordosis before surgery and more LOCL after LAMP (p < 0.001). After linear regression analysis for SCA and LOCL, preoperative SCA was negatively correlated with LOCL in the low SCA group (r = - 0.857, p < 0.001) and high SCA group (r = - 0.515, p = 0.034). However, there was no significant correlation between preoperative SCA and LOCL in the middle SCA group (r = 0.027, p = 0.881). CONCLUSIONS: Patients with lower SCA had more lordosis preoperatively and performed more LOCL after LAMP at 2 years of follow-up. Both too high or low preoperative SCA were negatively correlated with the degree of LOCL, while when the SCA fluctuates in a suitable range, it is easier to compensate for the changes of cervical sagittal alignment.

The Treatment Evaluation for Osteoporotic Kummell Disease by Modified Posterior Vertebral Column Resection: Minimum of One-Year Follow-Up.

BACKGROUND The aim of this study was to evaluate the clinical efficacy of modified posterior vertebral column resection (MPVCR) in treating osteoporotic Kummell disease. MATERIAL AND METHODS Between January 2013 and January 2015, 10 patients who were diagnosed with Kummell disease underwent MPVCR treatment, and their medical records were retrospectively collected. Every patient had follow-up for at least one year, with an average of 15 months. Clinical efficacy of MPVCR treatment was evaluated by kyphotic Cobb's angle, Oswestry disability index (ODI) and visual analogue scale (VAS) score. RESULTS Data analyses showed that operation time was 188.39±30.8 minutes, and blood loss was 860±130 mL with 600±200 mL of blood transfusions. VAS score decreased significantly after MPVCR surgery (p<0.001, Mann-Whitney U test). In addition, data analyses showed that postoperative ODI was less than preoperative ODI, which was a statistically significant difference (p<0.001, Mann-Whitney U test). X-ray radiograph showed that kyphotic Cobb's angle was 45°±12° preoperatively, 10°±4° two weeks after surgery, and 15°±6° at last follow-up, indicating that Cobb's angle after MPVCR surgery was significantly improved, compared to the preoperative scores (p<0.05, SNK-q test). CONCLUSIONS MPVCR surgery was an effective and safe surgical method to treat Kummell disease, especially for patients with kyphotic deformity and obvious nerve-oppressed symptoms. However, the long-term clinical effect still needs further studies.

Risk Factors Associated with Adjacent Vertebral Compression Fracture Following Percutaneous Vertebroplasty After Menopause: A Retrospective Study.

BACKGROUND Clinically, percutaneous vertebroplasty (PVP) is frequently applied to treat osteoporotic vertebral compression fracture (OVCF). It is believed that new compression fractures are more likely to occur adjacent to the PVP-treated segment, typically within 1 month after PVP. The purpose of this study was to investigate risk factors for adjacent vertebral compression fractures (AVCF) after PVP in patients with OVCF after menopause. MATERIAL AND METHODS Between Jun 2012 and Dec 2016, 412 patients were initially identified. We enrolled 390 patients in this study, and 22 were lost to follow-up. The medical records of the patients were retrospectively collected. Patients were followed up for at least 6 months, with an average follow-up period of 18 months. The potential risk factors investigated in this study included age, duration of menopause (DoM), preoperative vertebral compression, number of preoperative vertebral fractures (NPVF), bone mineral density (BMD), surgical approach (unilateral or bilateral), anesthesia methods, bone cement dose, complications (including COPD), and anti-osteoporosis treatment. Logistic regression analysis was used to determine the risk factors. RESULTS Sixty-eight patients were observed to have suffered from AVCF after PVP at the last follow-up. Univariate analysis showed that age, DoM, NPVF, BMD, COPD, and anti-osteoporosis treatment were the potential variables associated with the onset of AVCF (all P<0.05). Binary logistic regression analysis showed that the logistic regression equation was as follows: logit P=-3.10-1.07×X2+0.99×X3+2.15×X4 (where X2=BMD; X3=DoM; X4=NPVF), and "logit P" stands for the likelihood of developing an AVCF following PVP. CONCLUSIONS A long duration of menopause and preoperative multi-level vertebral fractures were the risk factors for AVCF in patients following PVP after menopause, while a high-level BMD acted in a protective role for AVCF development.

Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy.

BACKGROUND: Trimetazidine, as an anti-ischemic and antioxidant agent, has been demonstrated to have many cardioprotective effects. However, whether early administration of trimetazidine has an effect on diabetic cardiomyopathy and the mechanisms underlying the effect have not yet been elucidated. METHODS: We established a type 2 DCM rat model by high-fat diet and low-dose streptozotocin. Rats were separated into different groups: control, diabetes, and diabetes + trimetazidine (n = 6, each). Cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored. RESULTS: Rats with type 2 DCM showed severe insulin resistance, left ventricular dysfunction, increased cardiomyocyte apoptosis, and reduced cardiac autophagy. Collagen volume fraction (CVF) and perivascular collagen area/luminal area (PVCA/LA) ratio were significantly higher in the diabetic group than the control group. We found that trimetazidine treatment ameliorated metabolic disturbance and insulin resistance, reduced cardiomyocyte apoptosis, and restored cardiac autophagy. CVF and PVCA/LA ratio were also lower in the diabetes + trimetazidine group than the diabetic group (CVF, 4.75 ± 0.52 % vs. 11.04 ± 1.67 %, p < 0.05; PVCA/LA, 8.37 ± 0.51 vs. 17.97 ± 2.66, p < 0.05). Furthermore, trimetazidine inhibited phosphorylation of ERK and P38 MAPK to reduce myocardial fibrosis. Inhibited phosphorylation of AMPK was restored and the interaction between Bcl-2 and Beclin1 was enhanced in diabetes + trimetazidine group, resulting in the initiation of autophagy and alleviation of apoptosis. CONCLUSIONS: Early administration of trimetazidine could ameliorate diabetic cardiomyopathy by inhibiting myocardial fibrosis and cardiomyocyte apoptosis and enhancing autophagy. Therefore, trimetazidine may be a good choice in the prevention of diabetic cardiomyopathy if applied at the early stage of diabetes.

17ß-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway.

BACKGROUND Tumor necrosis factor-α (TNF-α) has been widely known to induce degeneration of nucleus pulposus cells (NPCs). 17ß-estradiol (17ß-E2) has been broadly proven for its function of suppressing cell apoptosis. The aim of this study is to explore whether 17ß-E2 protects apoptosis of human NPCs induced by TNF-α via the PI3K/AKT pathway. MATERIAL AND METHODS NPCs were divided into four groups: control, TNF-α (100 ng/mL), TNF-α (100 ng/mL) with pretreated 17ß-E2 (10 um/L), TNF-α (100 ng/mL) with pretreated 17ß-E2 (10 um/L) and MK2206 (10 um/L, inhibitor of the PI3K/AKT pathway). Flow cytometry was used to measure the apoptotic incidence. Inverted phase-contrast microscopy was used to accomplish the morphological observation for apoptosis of treated cells. Additionally, Cell Counting Kit 8 (CCK-8) assay was used to detected cell proliferation. Western blot and quantitative real-time PCR (qRT-PCR) were applied to explore the expression of pro-caspase-3, caspase-3/p17, cleaved PARP, PARP, Akt, and phospho-Akt (p-Akt). RESULTS First, inverted phase-contrast microscopy, CCK-8, and flow cytometry showed that TNF-α induced marked apoptosis, which was abolished by 17ß-E2. Furthermore, Western blot and qRT-PCR showed that 17ß-E2 protects TNF-α which can induced apoptosis by upregulating p-Akt, whereas Akt was essentially constant. Our data revealed that p-Akt expression peaked at 24 hours in a time-dependent manner (0-48 hours) after treating with TNF-α; and the p-Akt expression generally increased in a time-dependent manner (0-48 hours) after treating with TNF-α and 17ß-E2. CONCLUSIONS 17ß-E2 is shown to protect NPCs against TNF-α induced apoptosis by upregulating p-Akt in the PI3K/AKT pathway. 17ß-E2 generally increases expression of p-Akt.

Suprapedicular Foraminal Endoscopic Approach to Lumbar Lateral Recess Decompression Surgery to Treat Degenerative Lumbar Spinal Stenosis.

BACKGROUND To discuss the strategy of suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression and evaluate the safety and effectiveness of this strategy. MATERIAL AND METHODS Complete clinical information of 52 cases of lumbar lateral recess decompression with therapy of suprapedicular foraminal endoscopic approach were analyzed during the period from February 2010 to April 2014 in the Third Hospital of Hebei. All patients were followed up for 24 months, and VAS, JOA, ODI, and LRD were compared between preoperative and postoperative therapy and changes of FA. Intraoperative and postoperative complications were recorded and the safety of the surgery was evaluated. The surgical "excellent" and "good" rates were evaluated using MacNab score. RESULTS VAS scores for lumbago and leg pain at 3, 6, 12, and 24 months after surgery were significantly lower than before surgery (p<0.05). JOA scores at 12 and 24 months after surgery were significantly higher than before surgery (p<0.05). ODI at 12 and 24 months after surgery were significantly lower than before surgery (p<0.05). LRD after surgery was higher (p<0.05), and FA was lower than before surgery. CONCLUSIONS Use of the suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression is safe and effective, and this minimally invasive treatment can achieve satisfactory results, especially for elderly patients with complicated underlying diseases.

Unilateral Pedicle Screw Fixation with Bone Graft vs. Bilateral Pedicle Screw Fixation with Bone Graft or Cage: A Comparative Study.

BACKGROUND: The aim of this study was to explore the clinical efficacy of unilateral pedicle screw fixation with bone graft (UPSFB) in treating single-segment lumbar degenerative diseases (LDD), as compared to bilateral pedicle screw fixation with bone graft (BPSFB) or with cage (BPSFC). MATERIAL/METHODS: Medical records were retrospectively collected between 01/2010 and 02/2015 in Longyao County Hospital. According to surgical methods used, all patients were divided into 3 groups: UPSFB group, BPSFB group, and BPSFC group. Clinical outcomes were evaluated by blood loss, blood transfusion, duration of operation, hospital stay, postoperative complications, interbody fusion rate, reoperation rate, medical expenses, patient satisfaction survey, and JOA score. RESULTS: Ninety-five patients were included and underwent 2.5-year follow-up, with 7 patients lost to regular follow-up. As compared to the BPSFB group and BPSFC group, the UPSFB group had less blood loss and less blood transfusion, as well as shorter hospital stay (p<0.05). Medical expenses were far lower in the UPSFB group (p<0.001). There were no significant differences among the 3 groups in postoperative complications, interbody fusion rate, reoperation rate, JOA score, and patient satisfaction (all p>0.05). CONCLUSIONS: As compared to BPSFB and BPSFC, UPSFB has the same reliability and effectiveness in treating single-segment LDD with unilateral radicular symptoms in a single lower extremity, with the additional advantage being less expensive.

Incidence and risk factors for proximal junctional kyphosis: a meta-analysis.

PURPOSE: To analyse the incidence and risk factors associated with proximal junctional kyphosis (PJK) following spinal fusion, we collect relative statistics from the articles on PJK and perform a meta-analysis. METHODS: An extensive search of literature was performed in PubMed, Embase, and The Cochrane Library (up to April 2015). The following risk factors were extracted: age at surgery, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation, thoracoplasty, fusion to sacrum (S1), preoperative thoracic kyphosis angle (T5-T12) >40°, bone mineral density (BMD) and preoperative to postoperative sagittal vertical axis (SVA difference) >5 cm. Data analysis was conducted with RevMan 5.3 and STATA 12.0. RESULTS: A total of 14 unique studies including 2215 patients were included in the final analyses. The pooled analysis showed that there were significant difference in age at surgery >55 years old (OR 2.19, 95 % CI 1.36-3.53, p = 0.001), fusion to S1 (OR 2.12, 95 % CI 1.57-2.87, p < 0.001), T5-T12 >40° (OR 2.68, 95 % CI 1.73-4.13, p < 0.001), low BMD (OR 2.37, 95 % CI 1.45-3.87, p < 0.001) and SVA difference >5 cm (OR 2.53, 95 % CI 1.24-5.18, p = 0.01). However, there was no significant difference in gender (OR 0.98, 95 % CI 0.74-1.30, p = 0.87), combined anterior-posterior surgery (OR 1.55, 95 % CI 0.98-2.46, p = 0.06), use of pedicle screw at top of construct (OR 1.55, 95 % CI 0.67-3.59, p = 0.30), hybrid instrumentation (OR 1.31, 95 % CI 0.92-1.87, p = 0.13) and thoracoplasty (OR 1.55, 95 % CI 0.89-2.72, p = 0.13). The incidence of PJK following spinal fusion was 30 % (ranged from 17 to 62 %) based on the 14 studies. CONCLUSIONS: The results of our meta-analysis suggest that age at surgery >55 years, fusion to S1, T5-T12 >40°, low BMD and SVA difference >5 cm are risk factors for PJK. However, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation and thoracoplasty are not associated with PJK.

17ß-estradiol protects against apoptosis induced by interleukin-1ß in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13.

In our previous study, 17ß-estradiol was proved to protect rat annulus fibrosus cells against apoptosis induced by interleukin-1ß (IL-1ß). However, whether 17ß-estradiol has protective effect on rat nucleus pulposus cells remains unclear. The purpose of this study was to further explore the effects of 17ß-estradiol on rat nucleus pulposus cells based on IL-1ß-induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to detect apoptosis and revealed that IL-1ß induced notable apoptosis, which was reversed by 17ß-estradiol. Meanwhile, cell viability and binding ability were decreased by IL-1ß, but activated caspase-3 was increased. However, all of the detected effects of IL-1ß were eliminated by 17ß-estradiol. Furthermore, real-time quantitative RT-PCR was used to further find that IL-1ß downregulated expression level of type II collagen, aggrecan, tissue inhibitor of matrix metalloproteinase (TIMP)-1, while upregulated matrix metalloproteinase (MMP)-3, MMP-13 and Bcl-2, which was further confirmed by western blot. Finally, 17ß-estradiol was proved to abolish the above negative effects of IL-1ß. In summary, this work presented that IL-1ß maybe induced apoptosis of rat nucleus pulposus cells, which was resisted by 17ß-estradiol by down-regulating MMP-3 and MMP-13 via a mitochondrial pathway. This research provides a novel insight into the anti-apoptotic effect of 17ß-estradiol on IL-1ß-induced cytotoxicity, and may potentially lead to a better understanding of the clinical effects of 17ß-estradiol, especially in terms of intervertebral disc degeneration.

Prostaglandin F2α receptor silencing attenuates vascular remodeling in rats with type 2 diabetes.

BACKGROUND: Vascular remodeling is an important feature of diabetic macrovascular complications. The prostaglandin F2α receptor (FP), the expression of which is upregulated by insulin resistance and diabetes, is reportedly involved in myocardial remodeling. In this study, we aimed to investigate whether the FP receptor is implicated in diabetes-induced vascular remodeling. METHODS: A type 2 diabetic rat model was induced through a high-fat diet and low-dose streptozotocin (STZ). Thirty-two rats were randomized into four groups: control, diabetes, diabetes treated with empty virus and diabetes treated with FP receptor-shRNA. Then, we evaluated the metabolic index, FP receptor expression and vascular remodeling. We used FP receptor gene silencing in vivo to investigate the role that the FP receptor plays in the pathophysiologic features of vascular remodeling. RESULTS: Diabetic rats displayed increased levels of blood glucose, cholesterol, and triglycerides, as well as severe insulin resistance and FP receptor overexpression. In addition, increased medial thickness, excessive collagen deposition and diminished elastic fibers were observed in the diabetic rats, resulting in vascular remodeling. In the FP receptor-shRNA group, the medial thickness, collagen content, elastin/collagen ratio, and collagen I/collagen III content ratio were markedly decreased. Additionally, with FP receptor gene silencing, the JNK phosphorylation level was markedly decreased. CONCLUSIONS: Silencing of the FP receptor exerts a protective effect on diabetes-induced vascular remodeling, thereby suggesting a new therapeutic target for vascular remodeling in diabetes.

The relationship between laminoplasty opening angle and increased sagittal canal diameter and the prediction of spinal canal expansion following double-door cervical laminoplasty.

PURPOSE: To clarify the relationship between laminoplasty opening angle (LOA) and the increase in sagittal canal diameter (SCD) in double-door cervical laminoplasty (DDCL) and to predict the increase in SCD using the resulting formula. METHODS: We analyzed 20 patients with multilevel cervical spondylotic myelopathy who underwent DDCL between September 2010 and January 2013. The pre- and post-operative parameters of the cervical spinal canal were measured by computed tomography. We deduced a formula describing the relationship between LOA and the increase in SCD and used it to predict the increase in SCD of these patients as LOA increased. RESULTS: When the C3-C7 LOA was 25°-45°, the magnitude of the increase in SCD was notable (increases of 3.08-5.6 mm compared with the pre-operative SCD). When the C3-C7 LOA was more than 45°, the magnitude of the increase in SCD was relatively smaller; the increase in C3-C7 SCD with a 55° LOA was merely 0.4 mm more than with a 45° LOA. When LOA was 30° at C3-C6 or 40° at C7, the increase in SCD was more than 4 mm. When the C3-C6 LOA was 40°, SCD increased by more than 5 mm. CONCLUSIONS: The formula accurately showed the relationship between LOA and the increase in SCD in DDCL. Based on the LOA, increases in SCD following C3-C7 laminoplasty can be accurately predicted using this formula. This enables DDCL based on accurate individual LOAs, which prevents inadequate or excessive opening.

Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice.

Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.

17ß-Estradiol protects against apoptosis induced by levofloxacin in rat nucleus pulposus cells by upregulating integrin α2ß1.

Levofloxacin has been reported to have cytotoxicity to chondrocytes in vitro. And 17ß-estradiol has been widely studied for its protective effects against cell apoptosis. Based on apoptotic cell model induced by levofloxacin, the purpose of this study was to explore the mechanism by which 17ß-estradiol protects rat nucleus pulposus cells from apoptosis. Inverted phase-contrast microscopy, flow cytometry, and caspase-3 activity assay were used to find that levofloxacin induced marked apoptosis, which was abolished by 17ß-estradiol. Interestingly, estrogen receptor antagonist, ICI182780, and functional blocking antibody to α2ß1 integrin, both prohibited the effect of 17ß-estradiol. Simultaneously, levofloxacin decreased cellular binding ability to type II collagen, which was also reversed by 17ß-estradiol. Furthermore, western blot and real-time quantitative PCR were used to find that integrin α2ß1 was responsible for estrogen-dependent anti-apoptosis, which was time-response and dose-response effect. 17ß-estradiol was proved for the first time to protect rat nucleus pulposus cells against levofloxacin-induced apoptosis by upregulating integrin α2ß1 signal pathway.

Protection from renal fibrosis, putative role of TRIB3 gene silencing.

BACKGROUND: Renal fibrosis is thought to be the common pathway in most cases of chronic kidney disease. Recently, TRIB3 was found to play an important role in progression of cardiac fibrosis in an insulin-resistant state. We investigated whether TRIB3 might participate in the pathogenesis of renal fibrosis in insulin-resistant rats. METHODS: We randomly separated 40 male Sprague-Dawley into 4 groups for treatment (n = 10 each): control and high-fat diet (HFD) with TRIB3 siRNA adenovirus transfection, vehicle transfection or HFD alone. Insulin resistance markers were measured. Renal tissues were stained with hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff. RESULTS: Rats with HFD showed insulin resistance and TRIB3 overexpression. Upregulated TRIB3 expression could induce renal fibrosis accompanied by increased phosphorylation of extracellular signal-regulated kinase (ERK). Also, TRIB3 siRNA knockdown could ameliorate renal fibrosis, which was accompanied by decreased phosphorylation of ERK. CONCLUSIONS: TRIB3 gene silencing can attenuate renal fibrosis for beneficial effect on the development of renal fibrosis in chronic kidney disease in rat.