Surgical Treatment for Avulsion Fractures of the Anterolateral Ligament Associated with Periarticular Fractures of the Knee.

The existence and anatomy of the anterolateral ligament (ALL) of the knee are a somewhat controversial topic in orthopaedic surgery. The fixation of the avulsion fracture of the ALL (Segond fracture), associated with periarticular knee fractures, is rarely given much consideration while the major fracture fragments are reconstructed. This study aims to confirm the existence of ALL and evaluate the clinical outcomes of surgical management for avulsion fractures, involving its insertion, when associated with periarticular knee fractures. Twenty-three patients (16 males and 7 females) with avulsion fractures of the ALL associated with periarticular knee fractures were fixed with a spider plate, cannulated screw, or suture anchor. Eight patients were diagnosed with distal femoral fracture, 10 with tibial plateau fracture, and 5 with tibial eminence avulsion fracture. All patients underwent X-rays at follow-up. Clinical and functional outcomes were assessed with the pivot-shift test, objective and subjective International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The ALL was found and identified as a distinct ligamentous structure in all patients. Prior to Segond repair, patients had significantly more instability, as determined by pivot-shift test, than seen postoperatively (p < 0.0001). At final follow-up, the mean subjective IKDC score was 83.2 ± 10.3. Fourteen patients were graded A, 6 were graded B, and 3 was graded C on the IKDC objective score. The mean Lysholm score was 85.4 ± 12.2. The mean Tegner score was 7.5 ± 1.2. This study confirmed that the ALL is a distinct structure in the anterolateral portion of the knee. The fixation of the avulsion fracture of the ALL associated with periarticular knee fractures can be an effective procedure without specific complications. Long-term and comparative follow-up studies are necessary to confirm the effects.

Effective handling of nonlinear distortions in CO-OFDM using affinity propagation clustering.

We experimentally demonstrate a system-agnostic and training-data-free nonlinearity compensator, using affinity propagation (AP) clustering in single- and multi-channel coherent optical OFDM (CO-OFDM) for up to 3200 km transmission. We show that AP outperforms benchmark deterministic and clustering algorithms by effectively tackling stochastic nonlinear distortions and inter-channel nonlinearities. AP offers up to almost 4 dB power margin extension over linear equalization in single-channel 16-quadrature amplitude-modulated CO-OFDM and a 1.4 dB increase in Q-factor over digital back-propagation in multi-channel quaternary phase-shift keying CO-OFDM. Simulated results indicate transparency to higher modulation format orders and better efficiency when a multi-carrier structure is considered.

Complications associated with hyperextension bicondylar tibial plateau fractures: a retrospective study.

BACKGROUND: Hyperextension bicondylar tibial plateau fracture (HBTPF) is a particular form of tibial plateau fracture which has gained increasing interest recently but were rarely documented. In this study, we reported the characteristics, clinical intervention, and therapeutic outcomes of HBTPF patients. METHODS: From May 2015 to October 2017, clinical data of consecutive patients with bicondylar tibial plateau fractures (BTPF) who underwent surgical treatment in our hospital were retrospectively studied. The patients were allocated to either the HBTPF group (study group) or the non-HBTPF group (control group) based on the radiological features, and inclusion and exclusion criteria. Demographics, characteristics of knee joint injuries, complications, and outcomes were compared between the two groups. RESULTS: In total, 59 patients were included in this study. Among them, 17 patients with HBTPF were identified and 42 patients were diagnosed as non-HBTPF. No differences in age, sex, cause of injury, side of injury, site of injury, nerve injury, operation time, and treatment time and incision complication between HBTPF and non-HBTPF group. The incidence rate of popliteal artery injury in HBTPF group was 29.4 %, which was significantly higher than that of non-HBTPF group. Small bone chips on the lateral film were found in 94.1 % of the patients in HBTPF group, which was significantly higher than that of non-HBTPF group. The range of motion (ROM) and hospital for special surgery (HSS) score of HBTPF group were significantly lower than those of non-HBTPF group. CONCLUSIONS: HBTPF is a severe injury with a higher incidence rate of popliteal artery injury and worse outcomes than non-HBTPF. Small bone chips at the anterior margin of the proximal tibia on the lateral plain film might be a characteristic of HBTPF.

Total Synthesis of (-)-Oridonin: An Interrupted Nazarov Approach.

An enantioselective total synthesis of (-)-oridonin is accomplished based on a key interrupted Nazarov reaction. The stereochemistry of the Nazarov/Hosomi-Sakurai cascade was first explored to forge a tetracyclic skeleton with challenging quaternary carbons. A delicate sequence of two ring-rearrangements and late-stage redox manipulations was carried out to achieve the de novo synthesis of this highly oxidized ent-kauranoid.

Enantioselective syntheses and application of 4-epi-galiellalactone and the corresponding activity-based probe: from strained bicycles to strained tricycles.

The [6,5,5] tricyclic fungal metabolite galiellalactone is a Michael acceptor that has been demonstrated to be a covalent inhibitor for Signal Transducer and Activator of Transcription 3 (STAT3). Recognizing the ring strain associated with the skeleton of this natural product, we utilized 1R-5S-bicyclo[3.1.0]hexan-2-one as the starting material and developed two novel approaches to accomplish the enantioselective total synthesis of the C4 epimer of galiellalactone in 5 and 7 steps, respectively, which capitalized on an efficient radical cyclization/fragmentation cascade reaction. Furthermore, an activity-based probe of 4-epi-galiellalactone with a terminal alkyne tag was successfully prepared to enable the experiments of activity-based protein profiling (ABPP). Through western blot and proteomic analysis, we not only confirmed the known target STAT3, but also identified a new target protein ataxin-7, which formed a covalent bond with the probe in intact cells via the Cys-129 residue.

Is volar locking plate superior to external fixation for distal radius fractures? A comprehensive meta-analysis.

OBJECTIVE: The aim of this meta-analysis of randomized controlled trials (RCT) and retrospective cohort studies (CS) regarding the use of volar locking plate (VLP) and external fixation (EF) in distal radius fractures was to determine whether there was any evidence that one treatment was superior to the other. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Electrical databases (PubMed, EMBASE and the Cochrane library) were retrieved to find RCTs and CSs met the eligibility criteria. Two reviewers screened the studies, extracted the data and evaluated the methodological quality, and performed data analysis with RevMan 5.1. The publication bias was test by Stata 14.0. The Begg's and Egger's test were performed by Stata 14.0. The quality of evidence was graded according to the criteria of GRADE. We ultimately included ten RCTs and eleven CSs. RESULTS: A total of 1590 subjects were reported. Publication bias was detected by funnel plot in RCTs. VLP could provide better results such as DASH scores (RCT: MD = -6.12, 95%CI = -12.07-0.17; CS: MD = -6.43, 95%CI = -12.53-0.3), ulnar variance (RCT: MD = -0.81, 95%CI = -1.25-0.37) and infection rate (RCT: RR = 0.25, 95%CI = 0.10-0.65; CS: RR = 0.15, 95%CI = 0.06-0.40). There were no significant differences for G-W scores, VAS and grip strength between the VLP group and EF group. There was significantly greater loss of volar tilt (P = 0.01) and radial inclination (P = 0.02) in patients receiving EF, basing on the CSs. CONCLUSIONS: VLP could provide better results, such as DASH scores, ulnar variance, volar tilt, radial inclination and infection rate. The use of VLP appear to be associated with better results of ROM (flexion, pronation, supination and radial deviation), radiographic parameters (volar tilt and radial inclination) and lower total complication rate and CRPS rate in CSs. LEVEL OF EVIDENCE: Level 1, Therapeutic study.

Inflammatory milieu cultivated Sema3A signaling promotes chondrocyte apoptosis in knee osteoarthritis.

Osteoarthritis (OA) is the leading degenerative joint disease and featured by articular cartilage destruction, where chondrocyte apoptosis plays a critical role. Semaphorin-3A (Sema3A) has been implicated in OA chondrocyte physiology. In this study we aimed to uncover how Sema3A signaling is regulated in chondrocytes and investigate its role in OA chondrocyte survival. Here, we report that Sema3A and its receptor neuropilin-1 (Nrp1) are synchronously upregulated in cartilage chondrocytes of knee OA patients. Their expressions in chondrocytes could be induced by the stimulation of proinflammatory cytokines IL-1ß and TNF-α and subsequent transcriptional activation orchestrated by C/EBPß. The resulting excessive Sema3A signaling promotes chondrocyte apoptosis through impairing PI3K/Akt prosurvival signaling. These findings indicate a regulatory mechanism and a proapoptotic function of aberrant Sema3A signaling in OA chondrocytes, and suggest that targeting Sema3A signaling might interfere OA pathogenesis.

Total Synthesis of Maoecrystal†P: Application of a Strained Bicyclic Synthon.

A new strategy was devised for the total synthesis of highly oxidized ent-kauranoids. A highly regio- and diastereoselective intermolecular Diels-Alder cycloaddition involving a diene embedded in a substituted bicyclo[4.1.0] skeleton was used to assemble all carbon centers but C17 of the target molecule at an early stage of the synthesis. Subsequent synthetic steps, including redox manipulations, SmI2 -mediated cyclization, and isomerization reactions, afforded the antitumor natural product maoecrystal P.

Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis.

GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis.

Enantioselective Total Synthesis of (+)-Wortmannin.

A concise and enantioselective total synthesis of the potent PI3K inhibitor (+)-wortmannin is described. A Pd-catalyzed cascade reaction was first developed to connect a synthon derived from Hajos-Parrish ketone to a furan moiety. The subsequent Friedel-Crafts alkylation of the ß-position of a furan ring to an epoxide was optimized to establish the C10 quaternary center. (+)-Wortmannin was eventually accomplished by transformations following a late-stage oxidation of the furan allylic position. Kinome profiling and in vitro enzymatic assays were performed on 17-ß-hydroxy-wortmannin and an epoxide analogue.

Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling.

The development of multidrug resistance (MDR) remains a major limitation to successful chemotherapy in osteosarcoma. Preventing the introduction of MDR has been a research hotspot in clinical and investigational oncology. The aim of this study was to evaluate the preventive effects of tetrandrine (TET) against MDR in osteosarcoma. For this purpose, U-2OS human osteosarcoma cells were treated with paclitaxel alone or a combination of paclitaxel with TET. The cells treated with paclitaxel alone eventually acquired MDR along with the overexpression of and highly activated P-glycoprotein (Pgp), while the cells treated with the paclitaxel-TET combination were sensitive to chemotherapeutic drugs and expressed decreased levels of Pgp and less Pgp activity. The promoter activities of MDR gene 1 (MDR1) and nuclear factor (NF)­κB, and the expression levels of NF-κB and p-IκB-α were all enhanced in the cells cultured with paclitaxel alone. NF-κB DNA-binding activity and the binding ability of NF-κB to the MDR1 promoter were also enhanced in the cells cultured with paclitaxel alone compared to the control cells. However, the expression and activity of NF-κB were significantly decreased in the paclitaxel-TET combination-treated group as compared with the cells treated with paclitaxel alone. On the whole, our findings suggest that TET prevents paclitaxel-induced MDR by inhibiting Pgp overexpression through a mechanism that may involve the inhibition of NF-κB signaling in osteosarcoma.

Total Syntheses of (-)-Hibiscone C and Lysergine: A Cyclization/Fragmentation Strategy.

The first asymmetric total synthesis of (-)-hibiscone C and a concise synthesis of ergot alkaloid lysergine are described. Both syntheses were achieved using the radical cyclization/fragmentation strategy. This cascade reaction enabled the application of the strained bicycle as a synthon for the synthesis of highly substituted decalins in an efficient and stereoselective manner.

miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A.

Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.