Free iliac crest grafting technology for the management of critical-sized tibial bone defect.

OBJECTIVE: To introduce the method and experience of treating critical-sized tibial bone defect by taking large iliac crest bone graft. METHODS: From January 2020 to January 2022, iliac crest bone grafting was performed in 20 patients (10 men and 10 women) with critical-sized tibial bone defect. The mean length of bone defect was 13.59 ± 3.41. Bilateral iliac crest grafts were harvested, including the inner and outer plates of the iliac crest and iliac spine. The cortical bone screw was used to integrate two iliac bone blocks into one complex. Locking plate was used to fix the graft-host complex, supplemented with reconstruction plate to increase stability when necessary. Bone healing was evaluated by cortical bone fusion on radiographs at follow-up, iliac pain was assessed by VAS score, and lower limb function was assessed by ODI score. Complications were also taken into consideration. RESULTS: The average follow-up time was 27.4 ± 5.6 (Range 24-33 months), the mean VAS score was 8.8 ± 1.9, the mean ODI score was 11.1 ± 1.8, and the number of cortical bone fusion in the bone graft area was 3.5 ± 0.5. Satisfactory fusion was obtained in all cases of iliac bone transplant-host site. No nonunion, shift or fracture was found in all cases. No infection and bone resorption were observed that need secondary surgery. One patient had dorsiflexion weakness of the great toe. Hypoesthesia of the dorsal foot was observed in 2 patients. Ankle stiffness and edema occurred in 3 patients. Complications were significantly improved by physical therapy and rehabilitation training. CONCLUSION: For the cases of critical-sized tibial bone defect, the treatment methods are various. In this paper, we have obtained satisfactory results by using large iliac bone graft to treat bone defect. This approach can not only restore the integrity of the tibia, but also obtain good stability with internal fixation, and operation skills are more acceptable for surgeons. Therefore, it provides an alternative surgical method for clinicians.

Green finance, energy structure, and environmental pollution: Evidence from a spatial econometric approach.

The adjustment of green finance and energy structure is gradually becoming a new engine that reduces environmental pollution in China. In this paper, the energy structure is introduced in the process of discussing the impact of green finance on environmental pollution. We analyze the spatial correlation of green finance and study whether the adjustment of energy structure is affected by green finance and thus affects environmental pollution using a spatial econometric model. The results of empirical analysis show that green finance among provinces presents a significant spatial agglomeration, improving the green finance, and the energy structure can significantly reduce environmental pollution, and there are significant spatial spillover effects. There is inverted U-shaped relationship between energy structure and green finance in the national space, that is, after the green finance is raised to a certain extent, with the level of green finance once more, the energy structure will gradually improve, and then, green finance drives the reduction of environmental pollution by improving the energy structure. The results of the heterogeneity analysis show that compared with other regions, the improvement of the green finance in the eastern region has significantly improved the energy structure, and environmental pollution has also decreased every year.

Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study.

SHR-A1201 is an antibody-drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer.

Purpose: To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®. Methods: A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0-t and AUC0-∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over. Results: 48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®. Conclusions: Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin. Clinical trial registration: http://www.chinadrugtrials.org.cn, identifier [CTR20210375].

Synthesis of zwitterionic polymer modified graphene oxide for hydrophilic enrichment of N-glycopeptides from urine of healthy subjects and patients with lung adenocarcinoma.

As one of the most common and important post-translational modifications, protein N-glycosylation plays essential roles in many biological processes and have long been considered closely correlated with the occurrence and progression of multiple diseases. Systematic characterization of these disease-related protein N-glycosylation is one of the most convenient ways for new diagnostic biomarker and therapeutic drug target discovering. However, the biological samples are extremely complex and the abundance of N-glycoproteins are especially low, which make highly efficient N-glycoprotein/glycopeptide enrichment before mass spectrometry analysis a prerequisite. In this work, a new type of hydrophilic material (GO-pDMAPS) was prepared by in situ growth of linear zwitterionic polymer chains on the surface of GO and it was successfully applied for N-glycopeptide enrichment from human urine. Due to the excellent hydrophilicity and the facilitate interactions between this GO-pDMAPS and the targets, a total of 1426 N-glycosylated sites corresponding to 766 N-glycoproteins as well as 790 N-glycosylation sites corresponding to 470 N-glycoproteins were enriched and identified from urine of healthy subjects and patients with lung adenocarcinoma, respectively. Among which, 27 N-glycoproteins were expressed exclusively and 4 N-glycoproteins were upregulated at least 3 times comparing with the healthy group, demonstrating the tremendous potential of this new hydrophilic material for large scale and in depth N-glycoproteome research.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Effect of Etoricoxib on miR-214 and inflammatory reaction in knee osteoarthritis patients.

PURPOSE: To explore the effect of Etoricoxib on serum miR-214 expression level and inflammatory reaction in patients with knee osteoarthritis. METHODS: 96 patients with knee osteoarthritis admitted to our hospital (January 2019 to January 2020) were selected. 48 patients in the control group received Celecoxib and 48 patients in the observation group received Etoricoxib. The treatment effect, knee function, inflammatory factor level, immune function, and serum miR-214 expression level of the two groups were compared. 6 months after treatment, the incidence of complications (deformities, deep infections and severe pain) between the two groups was compared. RESULTS: (1) The observation group had a higher total effective rate (93.75%) in comparison to the control group (72.92%) (P<0.05). (2) Before treatment, the serum miR-214 expression level of the two groups was basically the same (P>0.05). After treatment, the serum miR-214 expression level of the two groups decreased significantly, with a more marked decrease in the observation group (P<0.05). (3) Before treatment, the levels of IL-1ß, TNF-α, and hs-CRP were not statistically different in the two groups (P>0.05). After treatment, IL-1ß, TNF-α, and hs-CRP in both groups decreased, and the decrease in the observation group was significantly greater (P<0.05). (4) Before treatment, the levels of CD3+CD8+ and CD3+ were basically the same in both groups (P>0.05). After treatment, the levels of CD3+CD8+ and CD3+ in the two groups increased, and for the observation group, were significantly greater P<0.05. (5) The Lysholm score was higher in the observation group than it was in the control group (inter-group effect: F = 58.070, P<0.001), and the Lysholm score of both groups tended to increase with time (time effect: F = 145.900, P<0.001). Grouping and time showed an interactive effect (interactive effect: F = 8.646, P<0.001). 6 months after treatment, observation group showed a lower complication rate when compared to the control groupt (P<0.05). CONCLUSION: Etoricoxib has a strong effect on patients with knee osteoarthritis. It can significantly reduce the expression of serum miR-214 and the level of inflammatory factors, and is worthy of clinical application.

CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro.

BACKGROUND: Nucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity. METHOD: In Vitro, H2O2 was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model. RESULT: In vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (H2O2) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3. CONCLUSIONS: The experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by H2O2 could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.

SIRT3 mitigates intervertebral disc degeneration by delaying oxidative stress-induced senescence of nucleus pulposus cells.

Senescence of nucleus pulposus (NP) cells (NPC) is a major cause of intervertebral disc degeneration (IVDD), so delay NPC senescence may be beneficial for mitigating IVDD. We studied the effect and mechanism of silent information regulator 2 homolog 3 (SIRT3) on NPC senescence in vivo and in vitro. First, we observed SIRT3 expression in normal and degenerated NPC with immunohistochemical and immunofluorescence staining. Second, using SIRT3 lentivirus transfection, reactive oxygen species probe, senescence-associated ß-galactosidase staining, polymerase chain reaction, and western blot to observe the oxidative stress, senescence, and degeneration degree among groups. Subsequently, pretreatment with adenosine monophosphate-activated protein kinase (AMPK) agonists and inhibitors, observing oxidative stress, senescence, and degeneration degree among groups. Finally, the IVDD model was constructed and divided into Ctrl, Vehicle, LV-shSIRT3, and LV-SIRT3 groups. X-ray and magnetic resonance imaging scans were performed on rat's tails after 1 week; hematoxylin and eosin and safranin-O staining were used to evaluate the degree of IVDD; immunofluorescence staining was used to observe SIRT3 expression; immunohistochemical staining was used to observe oxidative stress, senescence, and degeneration degree of NP. We found that SIRT3 expression is reduced in degenerated NP tissues but increased in H2 O2 -induced NPC. Moreover, SIRT3 upregulation decreased oxidative stress, delayed senescence, and degeneration of NPC. In addition, activation of the AMPK/PGC-1α pathway can partially mitigate the NPC oxidative stress, senescence, and degeneration caused by SIRT3 knockdown. The study in vivo revealed that local SIRT3 overexpression can significantly reduce oxidative stress and ECM degradation of NPC, delay NPC senescence, thereby mitigating IVDD. In summary, SIRT3 mediated by the AMPK/PGC-1α pathway mitigates IVDD by delaying oxidative stress-induced NPC senescence.

Development and validation of an ultrasensitive LC-MS/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial.

This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C18 analytical column (50 × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0 mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000 pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.

Missed diagnosis of femoral deep artery rupture after femoral shaft fracture: A case report.

BACKGROUND: Vascular injury is a rare complication of femoral shaft fractures, and rupture of the deep femoral artery is more difficult to diagnose because of its anatomical location and symptoms. Despite its low incidence, deep femoral artery rupture can lead to life-threatening outcomes, such as compartment syndrome, making early identification and diagnosis critical. CASE SUMMARY: A 45-year-old male patient was admitted to our hospital due to right lower limb trauma in a car accident, with complaints of severe pain and swelling on his right thigh. X-ray demonstrated a right femoral shaft fracture. During preparation for emergency surgery, his blood pressure and blood oxygen saturation dropped, and sensorimotor function was lost. Computed tomography angiography was performed immediately to confirm the diagnosis of rupture of the deep femoral artery and compartment syndrome, so fasciotomy and vacuum-assisted closure were performed. Rhabdomyolysis took place after the operation and the patient was treated with appropriate electrolyte correction and diuretic therapy. Twenty days after the fasciotomy, treatment with the Hoffman Type II External Fixation System was planned, but it was unable to be immobilized internally based on a new esophageal cancer diagnosis. We kept the external fixation for 1 year, and 3 years of follow-up showed improvement of the patient's overall conditions and muscle strength. CONCLUSION: For patients with thigh swelling, pain, anemia, and unstable vital signs, anterior femoral artery injury should be highly suspected. Once diagnosed, surgical treatment should be performed immediately and complications of artery rupture must be suspected and addressed in time.

Isoflurane cerebral preconditioning in a spontaneous hypertension rat model is associated with sphingosine kinases.

BACKGROUND: Isoflurane preconditioning could reduce different kinds of brain injury via sphingosine kinase (SPK). Both sphingosine kinase 1 and sphingosine kinase 2 play important roles in brain protection. However, the effects of isoflurane preconditioning on SPK expression in hypertension have not been investigated before. OBJECTIVES: To verify whether the neuroprotective effects of the anesthetic isoflurane after an ischemic injury are altered in hypertension and to identify its possible mechanisms involving SPK. MATERIAL AND METHODS: Wistar rats (control) and spontaneous hypertension rats (SHR) were exposed to isoflurane preconditioning before transient middle cerebral artery occlusion. The infarct volumes of cortical and subcortical brain areas were measured. The expression levels of SPK1 and SPK2 were measured before and after isoflurane preconditioning. RESULTS: In the SHR group, isoflurane preconditioning significantly reduced only the infarct volumes of the subcortical brain (p < 0.05), not of the cortical brain. After 3 h of isoflurane exposure and preconditioning, SPK2 levels in the SHR group increased in the cortical brain (p < 0.05), but not in the subcortical brain area, Unlike in the control group, isoflurane exposure and preconditioning could significantly increase SPK2 levels in both cortical and subcortical brain area. CONCLUSIONS: The brain protection effects induced by isoflurane preconditioning after an ischemic injury are mainly mediated by the SPK2 isoform and are somewhat impaired in hypertension. Attention should be paid to ischemic injury patients with hypertension.

Calcitonin inhibits intervertebral disc degeneration by regulating protein kinase C.

Intervertebral disc degeneration (IVDD) is the most critical factor that causes low back pain. Molecular biotherapy is a fundamental strategy for IVDD treatment. Calcitonin can promote the proliferation of chondrocytes, stimulate the synthesis of matrix and prevent cartilage degeneration. However, its effect and the underlying mechanism for IVDD have not been fully revealed. Chondrogenic specific matrix components' mRNA expression of nucleus pulposus cell (NPC) was determined by qPCR. Protein expression of NPC matrix components and protein kinase C was determined by Western blotting. A rat caudal intervertebral disc degeneration model was established and tested for calcitonin in vivo. IL-1 induced NPC change via decreasing protein kinase C (PKC)-ε phosphorylation, while increasing PKC-δ phosphorylation. Calcitonin treatment could prevent or reverse IL-1-induced cellular change on PKC signalling associated with degeneration. The positive effect of calcitonin on IVDD in vivo was verified on a rat caudal model. In summary, this study, for the first time, elucidated the important role of calcitonin in the regulation of matrix components in the nucleus of the intervertebral disc. Calcitonin can delay degeneration of the intervertebral disc nucleus by activating the PKC-ε pathway and inhibiting the PKC-δ pathway.

Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway.

Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo. We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway.

The protein tyrosine kinase inhibitor, Genistein, delays intervertebral disc degeneration in rats by inhibiting the p38 pathway-mediated inflammatory response.

The treatment for intervertebral disc degeneration (IDD) has drawn great attention and recent studies have revealed that the p38 MAPK pathway is a potential therapeutic target for delaying the degeneration of intervertebral discs. In this study, we analyzed a nature-derived protein tyrosine kinase inhibitor, Genistein, and its function in delaying IDD in rats both in vitro and in vivo via the p38 MAPK pathway. Nucleus pulposus cells treated with Genistein showed better function compared with untreated cells. Further study revealed that Genistein could play a protective role in IDD by inhibiting phosphorylation of p38, consequently inhibiting the p38 pathway-mediated inflammatory response. The rat IDD model also demonstrated that Genistein could effectively delay the degeneration of intervertebral disc tissue. The current study reveals new biological functions of Genistein, further demonstrates the effects of the p38 MAPK pathway on intervertebral disc degeneration, and deepens our understanding of the treatment and prevention of IDD.

IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway.

OBJECTIVES: The degeneration of intervertebral discs (IVD) is a risk factor for chronic low back pain. Anti-inflammation therapy could alleviate IVD degeneration. IL-10 is an important anti-inflammatory cytokine. However, the effect of IL-10 on IVD has not been fully revealed. The current study is to reveal the effect of IL-10 on IVD and its underlying mechanism. METHODS: IL-1ß was used to induce the degeneration of nucleus pulposus cells (NPCs). mRNA expression level was determined by qPCR. Protein expression level was determined by western blotting. Methylene blue was used to determined the expression of aggrecan. Immunocytochemical staining was used to determined the expression of collagen II. A rat caudal IVD degeneration model was established and used to evaluate the effect of IL-10 on IVD in vivo. RESULTS: IL10 could alleviated NPC degeneration in both morphology and extracellular matrix. IL-10 could increase the mRNA expression of Collagen II, Sox-9, but decrease the mRNA expression of IL-1ß, TNFα and Collagen X. IL-10 could also increase the protein level of Collagen II and aggrecan, but decrease that of Collagen X. Western blotting futher revealed the mechanism of the positive effect of IL-10 on IVD. IL-10 reduces phosphorylation level of p38 MAPK effectively. Rat caudal IVD degeneration model futher confirmed the positive effect of IL-10 on IVD degeneration and its mechanism in vivo. CONCLUSION: The current study demonstrates that exogenous IL-10 treatment can induce an anti-inflammatory response and inhibit p38 MAPK activation to delay IVD degeneration.

The Clinical Effect of Kyphoplasty Using the Extrapedicular Approach in the Treatment of Thoracic Osteoporotic Vertebral Compression Fracture.

BACKGROUND: To evaluate the clinical effect of kyphoplasty with the extrapedicular approach in the treatment of thoracic osteoporotic compression fractures, including upper, middle, and lower thoracic. METHODS: From April 2014 to December 2016, 50 cases (55 vertebrae) of thoracic osteoporotic fractures were treated with balloon kyphoplasty using the extrapedicular approach. Symptomatic levels ranged from T3 to T12 and were confirmed based on medical history, physical examination, and medical imaging. Pain relief, restoration of vertebral anterior and median height, and kyphosis correction were retrospectively compared before and after operation by using the visual analogue scale and radiography, respectively. In addition, bone cement leakage location and complications were recorded. RESULTS: Operations were successfully performed in all the cases, with an average surgery time of 77 minutes and follow-up period of 15 months (range, 6-36 months). The visual analogue scale scores at 3 days after operation and final follow-up were significantly reduced (P < 0.05). The vertebral anterior margin and median height on radiography after surgery were significantly improved (P < 0.05), and the kyphosis was significantly corrected. Four cases had cement leakage but no other adverse events. No blood vessel or spinal cord puncture injury during surgery or blood vessel embolism, pulmonary embolism, or fat embolism after surgery was found. CONCLUSIONS: Extrapedicular kyphoplasty is safe and effective in treating thoracic osteoporotic vertebral compression fractures. It can rapidly relieve backache, restore the body height of the fractured thoracic vertebra, and correct kyphosis. In addition, it can improve patient quality of life.

Development a hydrazide-functionalized thermosensitive polymer based homogeneous system for highly efficient N-glycoprotein/glycopeptide enrichment from human plasma exosome.

As one of the most common post-translational modifications, protein N-glycosylation precipitates in many important biological processes and has closely correlations with the occurrence and progression of multiple diseases. Plasma exosomes secreted by cells contain various bioactive N-glycoproteins which may serve as potential biomarkers for early disease diagnosis and treatment. However, the protein N-glycosylation profile in human plasma exosome is largely unknown, due to the technical challenges in glycoprotein identification. Signals of the rare N-glycoproteins/N-glycopeptides are severely suppressed by the abundant coexisting non-glycosylated counterparts in mass spectrometry analysis. Therefore, specific enrichment of N-glycoprotein/glycopeptide is a prerequisite for large scale N-glycosylation profiling. In this work, we developed a hydrazide functionalized thermosensitive polymer for efficient enrichment and in-depth identification of protein N-glycosylation in human plasma exosome by mass spectrometry. The polymer chains completely dissolve in the enrichment system to form a homogeneous solution. Therefore, efficient covalent coupling between the N-glycoprotein/glycopeptide and the polymer chain is achieved, due to the reduced interfacial mass transfer resistance and the densely packed accessible functional groups on the polymer chains. Furthermore, the thermosensitive polymer can be easily precipitated and recovered by simply rising the system temperature to above 34 °C. As a result, 329 N-glycosylation sites corresponding to 180 N-glycoproteins were enriched and identified from plasma exosomes of glioma patients and healthy subjects using the thermosensitive polymer. By quantitative comparison, we found 26 N-glycoproteins significantly changed between the glioma patients and the healthy subjects, demonstrating the potential of this new strategy for N-glycoproteome research of plasma exosome and biomarker discovery.

The morphing of geographical features by Fourier transformation.

This paper presents a morphing model of vector geographical data based on Fourier transformation. This model involves three main steps. They are conversion from vector data to Fourier series, generation of intermediate function by combination of the two Fourier series concerning a large scale and a small scale, and reverse conversion from combination function to vector data. By mirror processing, the model can also be used for morphing of linear features. Experimental results show that this method is sensitive to scale variations and it can be used for vector map features' continuous scale transformation. The efficiency of this model is linearly related to the point number of shape boundary and the interceptive value n of Fourier expansion. The effect of morphing by Fourier transformation is plausible and the efficiency of the algorithm is acceptable.

Content-Based Discovery for Web Map Service using Support Vector Machine and User Relevance Feedback.

Many discovery methods for geographic information services have been proposed. There are approaches for finding and matching geographic information services, methods for constructing geographic information service classification schemes, and automatic geographic information discovery. Overall, the efficiency of the geographic information discovery keeps improving., There are however, still two problems in Web Map Service (WMS) discovery that must be solved. Mismatches between the graphic contents of a WMS and the semantic descriptions in the metadata make discovery difficult for human users. End-users and computers comprehend WMSs differently creating semantic gaps in human-computer interactions. To address these problems, we propose an improved query process for WMSs based on the graphic contents of WMS layers, combining Support Vector Machine (SVM) and user relevance feedback. Our experiments demonstrate that the proposed method can improve the accuracy and efficiency of WMS discovery.