Surface bioactivation of Polyetheretherketone (PEEK) by magnesium chondroitin sulfate (MgCS) as orthopedic implants for reconstruction of skeletal defects.

Polyether-ether-ketone (PEEK) is clinically used as a bio-implant for the healing of skeletal defects. However, the osseointegration of clinical-sized bone grafts remains limited. In this study, surface-porous PEEK was created by using a sulfonation method and a metal-polysaccharide complex MgCS was introduced on the surface of sulfonated PEEK to form MgCS@SPEEK. The as-prepared MgCS@SPEEK was found to have a porous surface with good hydrophilicity and bioactivity. This was followed by an investigation into whether MgCS loaded onto sulfonated PEEK surfaces could promote osseointegration and angiogenesis. The in vitro results showed that MgCS@SPEEK had a positive effect on reducing the expression levels of inflammatory genes and promoting osteogenesis and angiogenesis-related genes expression levels. Furthermore, porous MgCS@SPEEK was implanted in critical-sized rat tibial defects for in vivo evaluation of osseointegration. The micro-computed tomography evaluation results revealed substantial bone formation at 4 and 8 weeks. Collectively, these findings indicate that MgCS@SPEEK could provide improved osseointegration and an attractive strategy for orthopaedic applications.

A TA/Cu2+ Nanoparticle Enhanced Carboxymethyl Chitosan-Based Hydrogel Dressing with Antioxidant Properties and Promoting Wound Healing.

Background: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public. Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings. Results: The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days). Conclusion: Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair.

Antibiotic-Impregnated Calcium Sulfate vs. Wound Irrigation-Suction to Treat Chronic Calcaneal Osteomyelitis.

BACKGROUND: Chronic osteomyelitis of calcaneus is not rare but is very hard to treat. Irrigation-suction and antibiotic-impregnated calcium sulfate following debridement are commonly used in managing chronic osteomyelitis, but their effects have rarely been compared. We aimed to compare the effectiveness of antibiotic-impregnated calcium sulfate with irrigation-suction in the treatment of patients with chronic calcaneal osteomyelitis. METHODS: From January 2011 to June 2018, adult patients at our institute with chronic osteomyelitis receiving treatment of either antibiotic-impregnated calcium sulfate (CS group) or irrigation-suction (IS group) following thorough debridement were screened and selected according to the inclusion and exclusion criteria. The clinical presentation, laboratory tests, complications, and the ultimate single-staged cure rate and recurrence were compared. RESULTS: A total of 61 patients, including 41 in the CS group and 20 in the IS group, were included in our study. Of the patients, 85.4% in the CS group and 60.0% in the IS group (P = .006) were successfully cured in the single stage, respectively, without infection recurrence. Lower infection recurrence rates with shorter hospital stay were found in the CS group than the IS group. Inflammatory biomarkers after surgery with both treatments were slightly decreased and not significantly different from preoperative or between-groups postoperative. Exudate from incision was found primarily in the CS group. CONCLUSION: This study demonstrates that both antibiotic-impregnated calcium sulfate and irrigation-suction after careful and thorough surgical debridement are generally effective in treating chronic calcaneal osteomyelitis. Antibiotic-impregnated calcium sulfate achieved a higher single-staged cure rate but was associated with an increased postoperative wound exudate. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Molecular Characterization of NSO Compounds and Paleoenvironment Implication for Saline Lacustrine Oil Sands by Positive-Ion Mass Spectrometry Coupled with Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry.

NSO compounds mainly exist in geological bodies in the form of nonhydrocarbons and asphaltenes with abundant geological and geochemical information. Combined with the gas chromatography mass spectrometry (GC-MS) technology, positive-ion electrospray ionization Fourier-transform ion cyclotron resonance MS (FT-ICR MS) was used to understand the composition and distribution characteristics of NSO compounds in the oil sands of the Dongpu Depression and to explore their paleoenvironmental significance. The results show that n-alkanes are characterized by an even carbon number and phytane dominance, suggesting a saline lacustrine environment. Certain abundance of nC37 and ß-carotane, high gammacerane content, and low diasterane content are detected in the analyzed samples, reflecting the saline-reducing paleoenvironment for the organic matter. Nine types of heteroatom compounds are detected: N1, N1O1, N1S1, O1, O1S1, O2, O2S1, S1, and S2. The main compounds are S1 and N1 compounds, followed by O1S1 compounds. The double-bond equivalent (DBE) value of S1 compounds is mainly distributed between 3 and 12, and the carbon number is mainly distributed between 18 and 35. The DBE value of N1 compounds is mainly distributed between 4 and 14, and the carbon number is mainly distributed in the range 15-35. Among the S1 compounds, DBE3 compounds (thiophenes) have relatively more sulfur-containing carotenoids (C40). The abundance of C40 S1 and the ratio of pyridine and its homologue DBE4-8/DBE9-12 N1 compounds show a good contrast with the paleoenvironment indicators of gammacerane/C30 hopane and diasterane/regular sterane. They can be used as a reference for the paleoenvironment index. Maturity is another factor affecting the distribution of NSO heteroatoms in the oil sands. NSO compounds are enriched in the DBE area with higher condensation, and the main peak carbon shifts forward. As the maturity increases, the relative abundance of N1 compounds increases, the aromatization intensifies, and carbon is broken into short chains. The research results shed light on the potential application of NSO compounds in petroleum exploration based on FT-ICR MS.

One-stage debridement and bone transport versus first-stage debridement and second-stage bone transport for the management of lower limb post-traumatic osteomyelitis.

BACKGROUND: Treatment of lower limb post-traumatic osteomyelitis used to be a staged process, with radical debridement of bone and soft tissues at first stage, followed by a second-stage limb reconstruction operation to restore the limb integrity. Some studies recently reported that achieving infection eradication and limb reconstruction at single-stage seems to be an effective method for lower limb infection, but a comparative study remains lacking. This study aims to compare the results of radical debridement combined with a first/second-staged osteotomy and bone transport, for the management of lower limb post-traumatic osteomyelitis. METHODS: From January 2013 to June 2018, a total of 102 patients with lower limb post-traumatic osteomyelitis met the criteria were included for analysis, in which 70 patients received one-stage debridement, antibiotic-loaded implantation, metaphysis osteotomy and bone transport were named as one-stage group, while 32 patients with first-stage debridement and antibiotic-loaded calcium sulfate implantation, second-stage osteotomy and bone transport were devised as two-stage group. The outcomes of hospitalization (hospital stay, costs of treatment, surgical time, antibiotic usage) and follow-up (infection-free, treatment failure, infection recurrence, external fixation index (EFI) and docking site union) between the two groups were retrospectively compared. RESULTS: For outcomes of hospitalization, patients in the one-stage group had batter results on hospital stay (18.2 days versus 28.9 days, P â€‹< â€‹0.05), surgical time (164.8 â€‹min versus 257.4 â€‹min, P â€‹< â€‹0.05), cost of treatment (¥101726.1 versus ¥126718.8, P â€‹< â€‹0.05) and the course of antibiotic usage (10.3 days versus 12.0 days, P â€‹< â€‹0.05). During the follow-up, 87.1% (61/70) patients in the one-stage group compared to 93.8% (30/32) patients in the two-stage group achieved infection-free (P â€‹> â€‹0.05) without any additional debridement operation. 94.3% (66/70) patients in the one-stage group earned wound healing after the operation, comparing to 96.9% (31/32) patients healed in the two-stage group (P â€‹> â€‹0.05). Uncontrolled infection was observed on 4 (5.7%) patients in the one-stage group and 1 (3.1%) patients in the two-stage group (P â€‹> â€‹0.05), with a result of three achieved infection free in the one-stage group and one patient suffered from amputation in each group respectively. 5 (7.2%) patients in the one-stage group and 1 (3.2%) patient in the two-stage group encountered with infection recurrence (P â€‹> â€‹0.05) and were well-managed with re-debridement and antibiotics usage. Significance was not found between two groups on EFI (74.8 days/cm versus 69.0 days/cm, P â€‹> â€‹0.05) and docking site nonunion rate (14.5% versus 18.9%, P â€‹> â€‹0.05), indicating that bone transport in different stages played a less essential role on bone generation process. The other complications, such as prolonged aseptic drainage [24.3% (17/70) versus 21.9% (7/32)], re-fracture [5.8% (4/69) versus 3.2% (1/31)], pin-tract infection [23.2% (16/69) versus 19.4% (6/31)], joint stiffness and deformity [26.1% (18/69) versus 32.3% (10/31)], also showed less significance when comparing between two groups (P â€‹> â€‹0.05), suggesting that different transport stages play little role on complications formation. CONCLUSIONS: One-stage radical debridement and bone transport was proven to be a safe and effective method for treating static (or near static) lower limb osteomyelitis. TRANSLATIONAL POTENTIAL STATEMENT: Translational potential statement One-stage debridement and bone transport is sample, effective and time-saving, with similar complications compared to conventional two-stage protocol. This treatment protocol might provide an alternative for the treatment of static (or near static) lower limb osteomyelitis.

Intramedullary reaming and irrigation and antibiotic-loaded calcium sulfate implantation for the treatment of infection after intramedullary nailing: a retrospective study of 19 cases.

BACKGROUND: The incidence of intramedullary infection is increasing with increased use of intramedullary fixation for long bone fractures. However, appropriate treatment for infection after intramedullary nailing is unclear. The purpose of this study was to report the results of our treatment protocol for infection after intramedullary nailing: intramedullary nail removal, local debridement, reaming and irrigation, and antibiotic-loaded calcium sulfate implantation with or without segmental bone resection and distraction osteogenesis. METHODS: We retrospectively reviewed the records of patients with an infection after intramedullary nailing treated from 2014 to 2017 at our center. Patients with follow-up of less than 24 months, received other treatment methods, or those with serious medical conditions were excluded from the analysis. Patients met the criteria were treated as described above, followed by distraction osteogenesis in 9 cases to repair bone defect. The infection remission rate, infection recurrence rate, and post-operative complication rates were assessed. RESULTS: A total of 19 patients were included in the analysis. All of patients had satisfactory outcomes with an average follow-up of 38.1 ± 9.4 months (range, 24 to 55 months). Eighteen patients (94.7%) achieved infection remission; 1 patient (5.3%) developed a reinfection that resolved after repeat debridement. Nine patients with bone defects (average size 4.7 ± 1.3 cm; range, 3.3 to 7.6 cm) were treated with bone transport which successfully restored the length of involved limb. The mean bone transport duration was 10.7 ± 4.0 months (range, 6.7 to 19.5 months). The majority of patients achieved full weight bearing and became pain free during the follow-up period. Postoperative complications mainly included prolonged aseptic drainage (7/19; 36.8%), re-fracture (1/19; 5.3%) and joint stiffness, which were successfully managed by regular dressing changes and re-fixation, respectively. CONCLUSION: Intramedullary nail removal, canal reaming and irrigation, and antibiotic-loaded calcium sulfate implantation (with or without distraction osteogenesis) is effective for treating infections after intramedullary nailing.

Single-stage treatment of chronic localized tibial osteomyelitis with local debridement and antibiotic-loaded calcium sulfate implantation: a retrospective study of 42 patients.

BACKGROUND: Although various methods have been introduced, the management of chronic tibial osteomyelitis remains a challenge. This study aims to assess a combined treatment method, local debridement combined with antibiotic-loaded calcium sulfate implantation, for the management of the local (Cierny-Mader type III) tibial osteomyelitis. METHODS: Forty-two patients (43 limbs) with type III tibial osteomyelitis, from January 2012 to December 2018, who received the treatment method mentioned above were included in the study. The infection remission rate, recurrence rate, complications rate, and bone healing rate were respectively analyzed. RESULTS: With a mean follow-up of 42.8 months, 38 limbs (37 patients) (88.4%, 38/43) achieved infection remission without recurrence. Among those patients pain, limitation of movement, sinus tracts, topical redness, and swelling were generally eliminated. Only 4 patients felt slight pain after a long-distance walk, while another 6 patients showed minor but acceptable discomfort in affected limbs. Five patients (11.6%) suffered from osteomyelitis recurrence that required secondary surgical and medical treatment, but no amputation was necessary to eliminate the infection. Prolonged aseptic drainage was the most frequent complication that was observed in 13 patients (30.0%). They were successfully managed by appropriate wound caring in 10 patients and by surgical intervention, months later, in 3 patients. According to the final X-ray examination, bone losses caused by local debridement were generally repaired, though the shape of the tibia was not well-restored to its initial form in 17 limbs. No fracture was recorded during follow-up. CONCLUSION: Local debridement combined with antibiotic-loaded calcium sulfate implantation is effective and safe in a single-stage treatment of chronic Cierny-Mader III tibial osteomyelitis.

Specific inhibition of FAK signaling attenuates subchondral bone deterioration and articular cartilage degeneration during osteoarthritis pathogenesis.

Osteoarthritis (OA), a disease of the entire joint, is characterized by abnormal bone remodeling and coalescent degradation of articular cartilage. We have previously found that elevated levels of H-type vessels in subchondral bone correlate with OA and that focal adhesion kinase (FAK) is critical for H-type vessel formation in osteoporosis. However, the potential role of FAK in OA remains unexplored. Here, we demonstrate that the p-FAK level was dramatically elevated in subchondral bone following anterior cruciate ligament transection (ACLT) in rats. Specific inhibition of FAK signaling with Y15 in subchondral bone resulted in the suppression of subchondral bone deterioration and this effect was mediated by H-type vessel-induced ectopic bone formation. Further, articular cartilage degeneration was also alleviated after Y15 treatment. In vitro, the p-FAK level was significantly elevated in mesenchymal stem cells (MSCs) from vehicle-treated ACLT rats as compared to that in MSCs from sham controls and Y15-treated ACLT rats. Elevated p-FAK level in MSCs promoted vascular endothelial growth factor (VEGF) expression, as demonstrated from the high VEGF level in the blood, subchondral bone, and conditioned medium (CM) of MSCs from vehicle-treated ACLT rats. The CM of MSCs from vehicle-treated ACLT rats might promote the angiogenesis of endothelial cells and the catabolic response of chondrocytes through the FAK-growth factor receptor-bound protein 2-mitogen-activated protein kinase-mediated expression of VEGF. The effect of the CM from MSCs of Y15-treated ACLT rats or that treated with a VEGF-neutralizing antibody on vessel formation and the catabolic response was lowered. Thus, the specific inhibition of FAK signaling may be a promising avenue for the prevention or early treatment of OA.

Extensive eggshell-like debridement technique plus antibiotic-loaded calcium sulphate for one-stage treatment of chronic calcaneal osteomyelitis.

BACKGROUND: Management of chronic calcaneal osteomyelitis is challenging. At present, there is still no widely accepted, simple, and effective surgical method to eradicate the infection and prevent osteomyelitis recurrence. The objective of this study was to assess the outcomes of one-stage treatment of chronic calcaneal osteomyelitis with a shape-preserving debridement technique combined with antibiotic-loaded calcium sulphate. METHODS: Between 2012 and 2018, 33 patients (33 limbs) with chronic calcaneal osteomyelitis were treated with a novel debridement technique, named "eggshell-like debridement", plus antibiotic-impregnated calcium sulphate. The infection remission rate, recurrence rate, and amputation rate were analyzed. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to assess postoperative hindfoot function. RESULTS: 26 patients (81.8%) achieved infection remission without recurrence. In the patients with osteomyelitis remission, pain, limitation of movement, sinus tracts, and typical redness and swelling were generally eliminated. Most of the patients could tolerate full weight-bearing without pain. The average AOFAS ankle and hindfoot score was 88 points (range, 67-100 points), implying the foot function was mostly restored. 6 patients (18.2%) had osteomyelitis recurrence but no amputation was required to elimilate the infection. CONCLUSIONS: Eggshell-like debridement combined with antibiotic-loaded calcium sulphate is an effective method for one-stage management of chronic calcaneal osteomyelitis. With the application of this technique, secondary autogenous bone or muscle flap grafts are unnecessary. The surgical procedure can be simplified whlie the hindfoot function is well preserved.

Inhibition of the proliferation, migration, and invasion of human breast cancer cells by leucine aminopeptidase 3 inhibitors derived from natural marine products.

Leucine aminopeptidase 3 is involved in the progression and metastasis of several cancers. This study aimed to screen anti-tumor lead compounds targeting leucine aminopeptidase 3. The compounds' suppression effect on enzyme activity and anti-tumor activity were evaluated through a series of assays. Leucine aminopeptidase 3 overexpression K562 cells were used as an enzyme source to screen 43 natural marine compounds. Compounds 5 and 6 exhibited high suppression effect on leucine aminopeptidase 3 activity. Cell activity tests indicated that both compounds have an anti-proliferative effect on triple-negative breast cancer cells. Wound healing assay and transwell invasion assay showed that both compounds could inhibit the migration and invasion of breast cancer cells. Immunoblot analysis exhibited that both compounds could downregulate the expression of metastasis-related proteins fascin and matrix metalloproteinase-2/9. A molecular dynamic simulation process was applied to discover the key features of compounds 5 and 6 in binding to leucine aminopeptidase 3 active site. This study described the anti-tumor effects of two leucine aminopeptidase 3 small molecule inhibitors. Taken together, compounds 5 and 6 could be used as anti-tumor lead compounds targeting leucine aminopeptidase 3.

A meta-analysis comparing intramedullary with extramedullary fixations for unstable femoral intertrochanteric fractures.

PURPOSE: To find out whether the intramedullary fixations are superior to the extramedullary fixations in treating unstable femoral intertrochanteric fractures (UFIFs). METHODS: The meta-analysis of randomized controlled trials (RCTs) was conducted by searching the PubMed, Cochrane Library, and Embase databases to evaluate functional scores, surgical outcomes, and adverse events in adult patients receiving intramedullary fixations in comparison to extramedullary fixations. Risk ratio (RR) or weighted mean difference (WMD)/standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated as effect sizes. RESULTS: A total of 18 RCTs, comprising 2414 patients, were included in this meta-analysis. Primary efficacy outcome: Parker scores [weighted mean difference, 1.10, 95% confidence interval (CI), 0.64-1.55; P < .0001] and Harris hip scores [risk ratio, 1.24, 95%CI, 1.09 -1.41; P = .0008] were higher in the intramedullary fixation group. Moreover, blood loss, operative time, length of incision, hospital stay, and implant failure were superior in the intramedullary fixation group. Other secondary efficacy outcome: No significant differences were found between the 2 groups in terms of fluoroscopy time, mortality, cut-out, nonunion, superficial wound infection, later fracture, and reoperation. CONCLUSIONS: This meta-analysis suggested that intramedullary fixation is more effective and safer than extramedullary fixation in treating UFIFs. Furthermore, blood loss, operative time, length of incision, hospital stay, and implant failure were superior in the intramedullary fixation group.

Infected bone resection plus adjuvant antibiotic-impregnated calcium sulfate versus infected bone resection alone in the treatment of diabetic forefoot osteomyelitis.

BACKGROUND: Managing with diabetic foot osteomyelitis (DFO) is challenging. Even after infective bone resection and thorough debridement, DFO is still difficult to cure and has a high recurrence rate. This retrospective study aims to compare the outcomes of two treatment methods, infected bone resection combined with adjuvant antibiotic-impregnated calcium sulfate and infected bone resection alone, for the treatment of diabetic foot osteomyelitis. METHODS: Between 2015 to 2017, 48 limbs (46 patients) with DFO met the criteria were included for assessment. 20 limbs (18 patients) were included in the calcium sulfate group (the CS group) in which vancomycin and/or gentamicin-impregnated calcium sulfate was used as an adjuvant after infected bone resection while 28 limbs (28 patients) as the control group were undergone infected bone resection only. Systemic antibiotics, postoperative wound care and offloading were continued to be applied following surgery in both groups. The time to healing, healing rate, recurrence rate and amputation rate were compared between the two groups. RESULTS: In total, 90% (18/20) limbs in the CS group as compared to 78.6% (22/28) infected limbs in the control group went to heal (P = 0.513). The Mean time to healing was 13.3 weeks in the CS group and 11.2 weeks in control group (P = 0.132). Osteomyelitis recurrence rate was 0% (0/18) in the CS group and 36.4% (8/22) in the control group (P = 0.014). Postoperative leakage in calcium sulfate group was 30.0% (6/20) with a mean duration of 8.5 weeks. Amputation rate in the control group was 7.1% (2/28) compared to 0% (0/20) in the CS group (P = 0.153). CONCLUSIONS: Antibiotic-impregnated calcium sulfate as an adjuvant prevents the recurrence of DFO but cannot improve the healing rate, reduce the postoperative amputation rate or shorten the time to healing. Prolonged postoperative leakage as the most common complication can be managed with regular dressing. LEVEL OF EVIDENCE: III, Retrospective Comparative Study.

A new method to evaluate the enzyme-suppressing activity of a leucine aminopeptidase 3 inhibitor.

The expression of leucine aminopeptidase 3 (LAP3) is associated with the prognosis for and malignant transformation of many types of tumors. Therefore, a LAP3 inhibitor may represent a new strategy for cancer therapy. Evaluating the suppression of enzyme activity by an LAP3 inhibitor is essential. Right now, leucine aminopeptidases (LAPs) purified from the porcine kidneys are the only enzymes that can be used to evaluate the suppression of enzyme activity by an LAP3 inhibitor. This approach cannot accurately reflect the suppression of human LAP3 by an inhibitor. The current study developed a new method with which to evaluate the suppression of enzyme activity by an LAP3 inhibitor. Total protein from K562 cells seldom catalyzed the LAP3 substrate. A lentivirus was used to induce K562 cells to overexpress LAP3 (K562-LAP3). After puromycin screening, flow cytometry data indicated that 98.8% of cells expressed green fluorescent protein. The expression of LAP3 in K562-LAP3 cells was also assessed using Western blotting. K562-LAP3 cells were lysed with ultrasonication. Total protein was used as an enzyme source and L-leucine p-nitroaniline hydrochloride was used as a substrate to measure enzyme activity. Total protein from K562-LAP3 cells catalyzed the substrate more than that from K562 cells did. The LAP3 inhibitor ubenimex was used as a positive control to evaluate the suppression of LAP3 enzyme activity. Results indicated that ubenimex significantly inhibited the enzyme activity of LAP3. This approach provides a convenient and accurate way to evaluate the suppression of enzyme activity by an LAP3 inhibitor.

New Method for Detecting the Suppressing Effect of Enzyme Activity by Aminopeptidase N Inhibitor.

Aminopeptidase N, also known as CD13, is a transmembrance protease with many functions. CD13 is involved in inflammatory diseases and cancers. A convenient and reliable laboratory test method for detecting the suppressing effects of enzyme activity would be useful for study of CD13 inhibitors. Porcine CD13 (pCD13) was traditionally considered an enzyme source but has significant practical disadvantages. pCD13 is not a human source, and the accuracy and reliability of experimental results are greatly reduced. In this study, a modified detection method with K562-CD13 monoclonal cells, a human-derived cell line, was established to detect the suppressing effects of enzyme activity by the CD13 inhibitor. In this method, K562-CD13 monoclonal cells were used as enzyme source and L-leucine p-nitroaniline hydrochloride as substrate. Using CD13 enzyme activity analyses, we found that the ability of the catalytic substrate was weaker in K562 cells than in the other cell lines, and K562-CD13 cells expressed significantly higher levels of CD13 enzyme activity than parental K562 cells. The enzyme activity of CD13 was detected with the new method after ubenimex treatment. The enzyme activity was significantly inhibited by ubenimex in a dose-dependent manner. In summary, this study proposes a sensitive, stable, and objective laboratory method for detecting the inhibitory effect of the CD13 inhibitor.

Comparison of the use of antibiotic-loaded calcium sulphate and wound irrigation-suction in the treatment of lower limb chronic osteomyelitis.

AIMS: We sought to compare the efficacy of antibiotic-loaded calcium sulphate with wound irrigation-suction in patients with lower limb chronic osteomyelitis. PATIENTS AND METHODS: Adult patients with lower limb chronic osteomyelitis treated at our hospital by means of segmental bone resection, antibiotic-loaded calcium sulphate implantation or wound irrigation-suction, followed by bone transport with external fixator from January 2011 to July 2015 were retrospectively evaluated. The clinical presentation, laboratory results, complications, docking obstruction, infection recurrence were compared. RESULTS: There were totally 74 patients met the inclusion criteria. Docking obstruction rate and infection recurrence were higher in the irrigation group with significant difference. The success rate of the first operation was 90.74% in the calcium sulphate group compared with 45% in the irrigation group. Postoperaton leakage of the incision happened more in the calcium sulphate group, but it wasn't a risk factor for docking obstruction and infection recurrence. Patients in the calcium sulphate group had shorter hospital stay and systemic antibiotic treatment, also with less external fixator index. CONCLUSIONS: The findings of our study suggest that antibiotic-loaded calcium sulphate implantation for lower chronic limb osteomyelitis was a more successful method than wound irrigation-suction, it greatly decreased infection recurrence and docking obstruction. Postoperative leakage after implantation didn't worsen patient's outcome.

CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents.

Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound.

[Acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages:a clinical randomized controlled trial].

OBJECTIVE: To compare the efficacy difference between acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages. METHODS: The randomized controlled prospective study method was adopted. Sixty cases of avascular necrosis of femoral head at Ficat-ArletⅠto Ⅱ stages were randomized into an acupotomy group (32 cases) and an acupuncture group (28 cases) by the third part. In the acupotomy group, the acupotomy was adopted for the loose solution at the treatment sites of hip joint, once every two weeks, totally for 3 times. In the acupuncture group, ashi points around the hip joint were selected and stimulated with warm acupuncture therapy, once every day, for 6 weeks. Harris hip score was observed before and after treatment. The efficacy was evaluated in the two groups. RESULTS: Harris hip score was improved significantly after treatment in the two groups (both P<0.05). The result in acupotomy group was better than that in the acupuncture group (P<0.05). The effective rate was 90.6% (29/32) in the acupotomy group, better than 75.0% (21/28) in the acupuncture group after treatment (P<0.05). CONCLUSIONS: Harris hip score and the effective rate in the acupotomy group are better than those in the treatment with routine acupuncture for avascular necrosis of femoral head at the early and middle stages.

Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is well established as a versatile intraarticular and intravenous (IV) antifibrinolytic agent that has been successfully used to control bleeding after total knee arthroplasty (TKA). The present meta-analysis aimed at assessing the effectiveness and safety of TXA in reducing blood loss and transfusion in TKA. METHODS: We searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to December 2013. Only randomized controlled trials (RCTs) were included in the present study. Two independent reviewers identified the eligible studies, assessed their methodological quality, and extracted data. The data were using fixed-effects or random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Subgroup analysis was performed according to the IV or intraarticular administration of TXA. RESULTS: Thirty-four RCTs encompassing 2,594 patients met the inclusion criteria for our meta-analysis. Our meta-analysis indicated that when compared with the control group, the IV or intraarticular use of TXA significantly reduced total blood loss, postoperative blood loss, Hb loss, and transfusion rate as well as blood units transfused per patient after primary TKA, but did not reduce intraoperative blood loss. No significant difference in deep vein thrombosis (DVT), pulmonary embolism, or other adverse events among the study groups. CONCLUSIONS: IV or intraarticular use of TXA for patients undergoing TKA is effective and safe for the reduction blood loss and blood transfusion requirements, yet does not increase the risk of postoperative DVT. LEVEL OF EVIDENCE: Level II.

[Effect on surface electromyography of deltoid in periarthritis patients under acupuncture stimulation].

OBJECTIVE: To explore the objective evaluation index of acupuncture effect through study on the differences of surface electromyography of deltoid before and after acupuncture at some specific points. METHODS: Twenty-six cases of periarthritis were treated with acupuncture at Jianyu (LI 15), Jianqian (Extra), Jianliao (TE 14) and Binao (LI 14). The treatment was given once every other day, six treatments were required. The deltoid myoelectricity indices were collected and analyzed before treatment, after treatment and after 5 s manipulations at each acupoint. RESULTS: Compared with the deltoid myoelectricity before treatment, there were statistically significant differences in the 2nd, 3rd and 5th manipulations during the acupuncture stimulation at Jianqian (Extra), the 2nd, 3rd and 6th manipulations at Binao ( LI 14) (all P < 0.05) and all the 6 manipulations at Jianyu (LI 15) (all P < 0.05). However, there was no statistically significant difference in all the 6 manipulations at Jianliao (TE 14) (all P > 0.05). And the differences of deltoid surface myoelectricity before and after the 6 acupuncture treatments were all with statistic significance (all P < 0.05). CONCLUSION: A certain therapeutic effect can be found in treatment of periarthritis with acupuncture. And the effect at Jianyu (LI 15) is proved to be the most obvious. Jianqian (Extra) and Binao (LI 14) are considered as the second obvious. While no significant effect can be found at Jianliao (TE 14).