Open Reduction and Internal Fixation for Supination-External Rotation Type IV Ankle Fractures by Means of Anterolateral and Posterolateral Approaches.

BACKGROUND: The present study aimed to analyze and compare the efficacy of the anterolateral and posterolateral approaches for surgical treatment of supination-external rotation type IV ankle fractures. METHODS: This retrospective study enrolled 60 patients (60 feet) with supination-external rotation type IV ankle fractures, including 30 patients (30 feet) treated by means of the anterolateral approach and 30 patients (30 feet) treated by means of the posterolateral approach. Postoperative clinical efficacy was compared between the groups based on operation time, intraoperative blood loss, postoperative complications, fracture healing time, visual analog scale scores, Short Form-36 Health Survey scores, and American Orthopedic Foot and Ankle Society scores. Comparisons between the two groups were performed using independent-samples t tests and analyses of variance. Intragroup differences were compared using paired t tests, and the χ2 test was used to compare categorical variables. RESULTS: All 60 included patients completed follow-up ranging from 12 to 18 months (mean duration, 14.8 ± 3.5 months). Although baseline characteristics were similar in the two groups, there were significant differences in operation time (86.73 ± 17.44 min versus 111.23 ± 10.05 min; P < .001) and intraoperative blood loss (112.60 ± 25.05 mL versus 149.47 ± 44.30 mL; P < .001). Although fracture healing time (10.90 ± 0.66 weeks versus 11.27 ± 0.94 weeks; P = .087) was shorter in the anterolateral group than in the posterolateral group, the difference was not significant. Postoperative complications occurred in one and three patients in the anterolateral and posterolateral approach groups, respectively. Visual analog scale scores were significantly lower in the anterolateral group than in the posterolateral group (1.43 ± 0.50 versus 1.83 ± 0.75; P = .019), although there was no significant difference in Short Form-36 Health Survey scores between the groups (73.63 ± 4.07 versus 72.70 ± 4.04; P = .377). However, American Orthopedic Foot and Ankle Society scores were higher in the anterolateral group than in the posterolateral group (80.43 ± 4.32 versus 75.43 ± 11.32; P = .030). CONCLUSIONS: Both the anterolateral and posterolateral approaches can achieve good results in the treatment of supination-external rotation type IV ankle fractures. Compared with the posterolateral approach, the anterolateral approach is advantageous for the treatment of supination-external rotation type IV ankle fractures given its safety and ability to reduce trauma, clear field of view revealed, and allow for exploration and repair of the inferior tibiofibular anterior syndesmosis within the same incision.

Cycloartenyl ferulate improves natural killer (NK) cell immunity against cancer by binding to IFNγ receptor 1.

Cycloartenyl ferulate (CF) is abundant in brown rice with multiple biologic functions. It has been reported to possess antitumor activity; however, the related mechanism of action of CF has not been clarified. Herein, we unexpectedly uncover the immunological regulation effects of CF and its molecular mechanism. We discovered that CF directly enhanced the killing capacity of natural killer (NK) cells for various cancer cells in vitro. In vivo, CF also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma dependent on NK cells. In addition, CF promoted anticancer efficacy of the anti-PD1 antibody with improvement of tumor immune microenvironment. Mechanistically, we first unveiled that CF acted on the canonical JAK1/2-STAT1 signaling pathway to enhance the immunity of the NK cells by selectively binding to interferon γ receptor 1. Collectively, our results indicate that CF is a promising immunoregulation agent worthy of attention in clinical application in the future. Due to broad biological significance of interferon γ, our findings also provide a capability to understand the diverse functions of CF.

Discovery and evaluation of cytisine N-isoflavones as novel EGFR/HER2 dual inhibitors.

Aberrant signaling of EGFR (ErbB) family members, in particular epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2), is associated with the occurrence and development of many types of human malignancies (e.g., breast, lung, and gastric cancers), and dual targeting of EGFR/HER2 by small-molecular inhibitors has proven to be an effective therapeutic approach for treating these cancers. Herein we extracted and isolated from the medicinal plant Sophora alopecuroides L. a new natural product, dubbed Cytisine N-methylene-(4',7-dihydroxy-3'-methoxy)-isoflavone (CNI1) that features a unique molecular framework. Our biochemical kinase assay suggested that one of its derivative CNI3 exhibited the best, micromolar (µM) inhibition activities against the EGFR (IC50 of 1.1 µM; Ki of 0.6 µM) and HER2 (IC50 of 3.5 µM; Ki of 1.8 µM) kinases. By contrast, another derivative CNI4 was most potent in inhibiting the EGFR-overexpressing A431 cancer cell line (IC50 of 45.5 µM) and the HER2-overexpressing BT-474 cancer cell line (IC50 of 32.9 µM), while the respective cellular activities of Lapatinib (a marketed drug) were 24.9 and 20.3 µM under the same assay condition. Moreover, both CNI3 and CNI4 showed desirable anti-metastatic efficacy in another two breast cancer models (viz., MDA-MB-231 and 4T1). In addition, we explored the inhibitory mechanisms of the CNIs against EGFR and HER2 by molecular dynamics simulation and revealed a novel mode of action that engages the cytisine and chromone moieties in CNIs. By combining structure- and ligand-based analysis, we further rationally engineered a new CNI compound that exhibits considerably improved cytotoxicity against both types of A431 and BT-474 cancer cells. Our study demonstrates the CNI compounds as a new class of EGFR/HER2 dual inhibitors and paves a way for their further development.

Efficacy of two different types of island flaps for the repair of diabetic foot ulcers on the heel.

Background: Heel ulcer of diabetic foot (DF) is a difficulty in clinical repair. The current study aimed to investigate the clinical efficacy of the medial plantar island flap (MPIF) and the sural nerve nutritional artery island flap (SNNAIF) for the repair of chronic diabetic foot ulcers (DFU) on the heel. Methods: Twelve patients with chronic DFU on the heel were admitted to our department from August 2018 to August 2020. Upon admission, ulcer debridement and bone cement filling were performed for 2-3 weeks to control infection. Digital subtraction angiography (DSA) or computed tomography angiography (CTA) of the lower limb was performed to assess vascular status. Then, 5 patients were repaired with MPIF and 7 patients with SNNAIF. Results: The MPIF survived completely in 5 cases; SNNAIF was used in 7 cases, and 6 cases survived completely. Meanwhile, 1 patient who underwent SNNAIF presented with partial necrosis of the distal end of the flap. Then, it healed after debridement and dressing changes. All 12 flaps were followed up for 6-12 months. The flaps had a soft texture, and their shape was satisfactory. In 2 cases, SNNAIFs re-ruptured 8 months after surgery. However, they healed after dressing changes and weight-bearing reduction. During the 10-month follow-up, the sensory recovery of MPIF in 5 cases was satisfactory because the flap contained medial plantar cutaneous nerve. Meanwhile, 7 patients who underwent SNNAIF repair had poor sensory recovery. All patients had good dorsiflexion and plantarflexion of the ankle with satisfactory function. Conclusions: Both the MPIF and SNNAIF flaps had a high survival rate and are feasible for DFU repair with good clinical outcomes. If DSA or CTA shows that the medial plantar artery is unobstructed and the heel wound is small, MPIF can retain sensory function and wear resistance. It is the first choice for repairing diabetic foot ulcers on the heel. If the heel wound are large or DSA or CTA shows that the posterior tibial artery is occluded and the peroneal artery is unobstructed, SNNAIF repair is safer.

Repair of tophus wound of the heel with sural nerve nutrition flap with peroneal artery perforating branch: a retrospective study.

BACKGROUND: This study was to investigate the clinical effect of a sural nerve nutrition flap with peroneal artery perforator for repairing tophus wound of the heel. METHODS: Over a 5-year period, 7 elderly male patients with tophus ulceration of the heel were admitted with exposed Achilles' tendon, and a chronic unhealed wound. Debridement, expansion and vacuum sealing drainage (VSD) lavage were performed initially, with simultaneous uric acid-lowering treatment. A 4×6-8×10 cm sural nerve nutrition flap with peroneal artery perforator was the secondary repair after further debridement of the wound. Preoperative Doppler ultrasound located the penetrating point of the peroneal artery perforator as the rotation point of the flap, and the line between the midpoint of the Achilles' tendon and the lateral malleolus and the midpoint of the popliteal fossa 5° above the front of Achilles' tendon was the axis. The patients were treated postoperatively with anti-inflammatory, anticoagulant and spasmolytic drugs and other rehydration therapy, and allopurinol was continued to control uric acid. The blood supply and temperature of the flap and wound healing were monitored. RESULTS: All 7 flaps survived completely after operation, with 1 case of postoperative wound discharge that finally healed after dressing change and 1 case of skin flap redness and swelling, which improved after strengthening anti-infection treatment. All 7 patients were followed up for 6-12 months (average 10 months). The skin flaps were soft in texture, with good color and appearance, and no recurrence of ulceration. The dorsal extension and plantar flexion of the ankle joint were good, and function was satisfactory. CONCLUSIONS: The sural nerve nutrition flap with peroneal artery perforator has double blood supply, strong anti-infective ability, relatively fast tissue healing process, simple operation and high survival rate, making it ideal for repairing tophus wounds of the heel.

Comparison of the modified sinus tarsi approach versus the extensile lateral approach for displaced intra-articular calcaneal fractures.

BACKGROUND: This study sought to assess and compare the clinical efficacy and complications of a modified sinus tarsi approach (MSTA) and the extensile lateral approach (ELA) in the treatment of displaced intra-articular calcaneal fractures. METHODS: This retrospective study enrolled 108 patients (117 feet) with Sanders II-IV calcaneal fractures, including 52 patients (56 feet) in the MSTA group and 56 patients (61 feet) in the ELA group. The functional and radiological results of the affected feet were analysed retrospectively. Functional evaluation included American Orthopaedic Foot and Ankle Society (AOFAS), visual analog scale (VAS), and Short Form-36 Health Survey (SF-36). Radiological evaluation included preoperative and postoperative changes in the Bohler Angle, Gissane Angle, length, width, and height of the calcaneus. The postoperative complications were also collected and analysed. The independent-samples t-test and analysis of variance (ANOVA) were employed to compare differences between the two groups. Differences within the same group were compared by paired Student's t-test, and categorical variables were compared using the chi-square test. RESULTS: The postoperative functional and radiological results showed that the mean AOFAS, VAS and physical component summary of SF-36 scores in the MSTA group were higher than those in the ELA group (P<0.05). After surgery, the Bohler and Gissane angles were significantly improved in both groups, as were the length, width, and height of the calcaneus; no statistically significant differences existed between the two groups. The incidences of wound healing complications and postoperative sural nerve injury were lower in the MSTA group than in the ELA group (P<0.000). CONCLUSIONS: The MSTA can achieve similar effects to the ELA in terms of anatomical reconstruction and functional recovery. It also can also effectively reduce the incidences of wound healing complications and postoperative sural nerve injury, and shorten the length of hospital stay.

Gas-phase complexation of α-/ß-cyclodextrin with amino acids studied by ion mobility-mass spectrometry and molecular dynamics simulations.

Cyclodextrins (CDs) are a class of macrocyclic molecules that have exhibited many promising applications in various fields. The knowledge of the complexation modes and recognition mechanisms of CDs with their guests are of paramount importance for rational design of more variants with controlled properties. Herein we investigated the binding conformations and the structural characteristics of α-/ß-CD with three amino acids (AA, AA=Gly, L-Leu, L-Phe) in the gas phase by a combined experimental and computational approach. Electrospray ionization-mass spectrometry suggested the formation of 1:1 anionic complexes between CDs and AAs and the complex anions were further identified by tandem mass spectrometry. Moreover, ion mobility-mass spectrometry experiments revealed the inclusion complexation adopted for [α-CD+Gly]- as well as ß-CD with either amino acid, whereas [α-CD+Leu]- and [α-CD+Phe]- favored an exclusion conformation, indicating size-dependent binding modes. The association is primarily driven by polar interactions via the formation of hydrogen bonds. Furthermore, the relative dynamic stabilities of the complex ions were observed to be in correlation with the gas-phase basicities of the deprotonated amino acid and CD anions. These above findings are well in line with our atomistic molecular dynamics simulation results. This study advances our understanding of the mechanisms underlying CD host-guest recognition.

X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

INTRODUCTION: It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. METHODS: We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. RESULTS: The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. DISCUSSION: Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury.

Stepwise substrate translocation mechanism revealed by free energy calculations of doxorubicin in the multidrug transporter AcrB.

AcrB is the inner membrane transporter of the tripartite multidrug efflux pump AcrAB-TolC in E. coli, which poses a major obstacle to the treatment of bacterial infections. X-ray structures have identified two types of substrate-binding pockets in the porter domains of AcrB trimer: the proximal binding pocket (PBP) and the distal binding pocket (DBP), and suggest a functional rotating mechanism in which each protomer cycles consecutively through three distinct conformational states (access, binding and extrusion). However, the details of substrate binding and translocation between the binding pockets remain elusive. In this work, we performed atomic simulations to obtain the free energy profile of the translocation of an antibiotic drug doxorubicin (DOX) inside AcrB. Our simulation indicates that DOX binds at the PBP and DBP with comparable affinities in the binding state protomer, and overcomes a 3 kcal/mol energy barrier to transit between them. Obvious conformational changes including closing of the PC1/PC2 cleft and shrinking of the DBP were observed upon DOX binding in the PBP, resulting in an intermediate state between the access and binding states. Taken together, the simulation results reveal a detailed stepwise substrate binding and translocation process in the framework of functional rotating mechanism.