Recombinant human growth hormone treatment of mice suppresses inflammation and apoptosis caused by skin flap ischemia-reperfusion injury.

BACKGROUND: This study was to investigate the effects of recombinant human growth hormone (rhGh) on ischemia-reperfusion (I/R) injury of mouse flaps. METHODS: Healthy mice were randomly divided into four groups as follows: sham group, the IR group, the sham+rhGH group and the IR+rhGH group, with 12 mice in each group. Skin pathology was tested by hematoxylin and eosin staining. The flap survival of each group was measured after 7 days. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using corresponding kit. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum and flap were respectively measured by performing enzyme-linked immunosorbent assay and quantitative real-time (qRT)-PCR. The expressions of cleaved caspase-3, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), vascular endothelial growth factor (VEGF), MnSOD, toll-like receptor 4 (TLR4), and galectin-3 and (p)-p65 were analyzed by RT-PCR or/and Western blot. RESULTS: Prophylactic systemic application of recombinant human GH reduced the pathological damage of skin IR and significantly improved the flap survival of IR in mice, accompanied by elevation of VEGF. After administration of recombinant human GH, the activity of SOD/MnSOD in the flap was significantly increased, while the content of MDA was decreased. Cleaved caspase-3 and Bax were downregulated and Bcl-2 was upregulated in IR+rhGH group, compared to IR group. The levels of TLR4, Galectin-3 and p-p65 were decreased by rhGH. CONCLUSION: rhGH had protective effects on flap IR injury, and can be used as a drug intervention target for the treatment of skin flap IR injury.

Benzoylaconine Protects Skeletal Muscle Against Ischemia-Reperfusion Injury Through Activation of IF1-Dependent AMPK/Nrf2 Axis.

Background: Aconitum carmichaelii (Fuzi) has been conventionally used to cure a variety of ailments, such as pain, cold sensations, and numbness of limb muscles (Bi Zheng) in China. Our prior investigations identified Benzoylaconine (BAC) as a bioactive alkaloid derived from Aconitum carmichaelii, with other studies also demonstrating its significant pharmacological potential. Purpose: This study aimed to explore the potential of BAC as a protective agent against skeletal muscle ischemia-reperfusion (I/R) injury and to elucidate the underlying mechanisms. Methods: In vivo models involved subjecting Sprague-Dawley rats to I/R through femoral artery ligation followed by reperfusion, while in vitro models utilized C2C12 cells subjected to hypoxia/reoxygenation (H/R). CCK-8 assay was used to assess cell viability. TUNEL staining and flow cytometric analysis were used to measure cell apoptosis. Biochemical assay was used to assess skeletal muscle injury and oxidative stress. Immunofluorescence and Western blot were performed to determine protein levels. Results: BAC effectively protected muscle tissue from I/R injury, enhancing cell viability (p<0.01), elevating SOD levels (p<0.05), and reducing CK (p<0.01), LDH (p<0.01), ROS (p<0.01), MDA (p<0.01), and apoptosis-related molecules in vivo and in vitro (p<0.05, p<0.01). Mechanistically, BAC increased the expression of IF1, phosphorylated AMPK, facilitated the translocation of nuclear Nrf2, and induced the expression of HO-1 (p<0.01). Notably, AMPK inhibitor Compound C significantly hindered the ability of BAC to ameliorate H/R-induced cell injury (p<0.05), oxidative stress(p<0.01), and apoptosis (p<0.05), as well as promote Nrf2 nuclear translocation (p<0.01). Moreover, silencing of IF1 with siRNA abolished BAC-induced activation of AMPK/Nrf2 axis (p<0.01). Conclusion: Our study provides novel evidence supporting the potential of BAC as a myocyte-protective agent against I/R injury, and we establish a previously unknown mechanism involving the activation of the IF1-dependent AMPK/Nrf2 axis in mediating the protective effects of BAC.

Preliminary Outcomes of Calcaneal Body Lengthening for the Calcaneus Shortening.

For lengthening irregular bones, such as calcaneus, there are few reports in the literature. This study aimed to introduce the treatment strategy and preliminary outcomes for calcaneus shortening using calcaneal body lengthening. From January 2017 to January 2022, calcaneal lengthening was conducted for three patients (two males and one female) who suffered from traumatic calcaneal shortening. The Achilles tendon was lengthened in one patient. After osteotomy of the calcaneus, an Ilizarov frame was used to gradually (1 mm/day) distract the calcaneal fragment. The lengthening procedure was stopped when the calcaneal height and length were restored based on radiography. The fixator was removed after bone union. The average follow-up length was 18 months (range, 14-24 months). X-ray was used for radiological assessments. Patients reported satisfaction using the 100-mm visual analog scale (VAS). Clinical outcome was evaluated following the American Orthopedic Foot and Ankle score. All data were assessed by two physicians blind to clinical assessments. The wound healed primarily in three cases. The bone got solid union without refracture and malunion. The distraction time was 30 days (range, 25-45 days). The fixation time was 113.3 days (average, 80-150 days). Calcaneal lengthening was 26 mm (range, 15-43 mm). The height and length of the calcaneus were restored nearly to the same as the opposite foot. The mean preoperative calcaneal pitch angle increased from 2.6 degrees to an average of 19.0 degrees after the surgery. The AOFAS score increased from 60.0 to 86.0. One patient experienced pin infection. The infection healed after changing the dressing. Calcaneal lengthening using an Ilizarov external fixator is a preferable technique to restore the length and height of the calcaneus and can achieve satisfactory foot function.

Partial talar replacement with a novel 3D printed prosthesis.

BACKGROUND: The treatment of talus avascular necrosis (AVN) is challenging owing to its unique anatomical features. Despite decades of studies, till date, there is no appropriate treatment for talus AVN. Therefore, surgeons need to develop newer surgical methods. In the present study we introduce a new surgical method, 3D printed partial talus replacement (PTR), to treat partial talus necrosis and collapse (TNC). METHODS: A male patient with talus AVN underwent PTR in our hospital. The morphology of the talus was quantified using 3D computed tomography (CT) imaging. A novel 3D printed titanium prothesis was designed and manufactured according to the findings of the CT imaging. The prosthesis was applied during talus replantation surgery to reconstruct the anatomical structure of the ankle. The follow-up period for this patient was 24 months. The visual analog scale (VAS) scores before and after surgery, American Orthopedic Foot and Ankle Score (AOFAS), ankle range of motion, and postoperative complications were recorded to evaluate the prognosis. RESULTS: The anatomical structure of the talus was reconstructed. The patient was satisfied with the effects of treatment, recovery, and function. The VAS score decreased from 5 to 1. The AOFAS improved from 70 to 93. The range of motion remained the same as that during the pre-operation. The patient returned to a normal life. CONCLUSION: 3D printed PTR is a new surgical method for talus AVN that can provide satisfactory outcomes. In future, PTR might be an effective and preferential treatment for the treatment of partial talus AVN and collapse.

Network pharmacology-based approach uncovers the pharmacodynamic components and mechanism of Fructus Tribuli for improving endothelial dysfunction in hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT), a traditional Chinese medicinal herbal, has been used for the clinical treatment of cardiovascular diseases for many years and affects vascular endothelial dysfunction (ED) in patients with hypertension. AIM OF THE STUDY: This study aimed to demonstrate the pharmacodynamic basis and mechanisms of FT for the treatment of ED. MATERIALS AND METHODS: The present study used ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze and identify the chemical components of FT. The active components in blood were determined after the oral administration of FT by comparative analysis to blank plasma. Then, based on the active components in vivo, network pharmacology was performed to predict the potential targets of FT in treating ED. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed, and component-target-pathway networks were constructed. Interactions between the major active components and main targets were verified by molecular docking. Moreover, spontaneously hypertensive rats (SHRs) were divided into the normal, model, valsartan, low-dose FT, medium-dose FT, and high-dose FT experimental groups. In pharmacodynamic verification studies, treatment effects on blood pressure, serum markers (nitric oxide [NO], endothelin-1 [ET-1,], and angiotensin Ⅱ [Ang Ⅱ)]) of ED, and endothelial morphology of the thoracic aorta were evaluated and compared between groups. Finally, the PI3K/AKT/eNOS pathway was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot of the thoracic aorta of rats in each group to detect the mRNA expression of PI3K, AKT, and eNOS and the protein expression of PI3K, AKT, p-AKT, eNOS, and p-eNOS. RESULTS: A total of 51 chemical components were identified in FT, and 49 active components were identified in rat plasma. Thirteen major active components, 22 main targets, and the PI3K/AKT signaling pathway were screened by network pharmacology. The animal experiment results showed that FT reduced systolic blood pressure and ET-1 and Ang Ⅱ levels and increased NO levels in SHRs to varying degrees. The therapeutic effects were positively correlated with the oral dose of FT. Hematoxylin-eosin (HE) staining confirmed that FT could alleviate the pathological damage of the vascular endothelium. qRT-PCR and Western blot analysis confirmed that up-regulated expression of the PI3K/AKT/eNOS signaling pathway could improve ED. CONCLUSIONS: In this study, the material basis of FT was comprehensively identified, and the protective effect on ED was confirmed. FT had a treatment effect on ED through multi-component, multi-target, and multi-pathways. It also played a role by up-regulating the PI3K/AKT/eNOS signaling pathway.

Long-term outcomes of toe replantation: A review of ten cases.

BACKGROUND: Foot injuries due to vehicular or other accidents are common. However, complete toe amputation is rare. This study explored the current protocols and clinical significance of toe replantation. METHODS: From December 2011 to December 2018, ten patients with 13 severed toes underwent toe replantation in our hospital. Seven cases were replanted antegrade, and three cases were replanted retrograde. RESULTS: All patients were followed for two to three years after toe replantation. One big toe underwent necrosis, while the other 12 toes survived completely. The appearance and feel of the successfully replanted toes were satisfactory, and the patients exhibited a normal gait. CONCLUSION: Toe replantation can achieve an acceptable appearance and function of the foot and considerably reduce the psychological effects experienced by the patients. Increased clinical attention and application of toe replantation are needed. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Application of cryopreserved autologous skin replantation in the treatment of degloving injury of limbs.

Degloving injury is a common and intractable injury with the bone and tendon exposed and contamination, the stripped skin cannot be replanted immediately and will be discarded, although auto-graft is needed for subsequent wound repair. In this study, autologous skin cryopreservation technique was applied to the treatment of severe limb degloving injuries. The clinical data of 9 patients from January 2016 to December 2018 were analyzed retrospectively. Among the 9 cases, 1 case developed necrosis due to wound infection, and the rest survived 60-100%. The replanted cryopreserved skin were soft and resilient, with poor sensory recovery, varying degrees of discoloration and no hair growth. Cryopreservation provides more time for improving the wound and whole-body condition. The frozen skin had good quality and high survival rate. Our study can effectively use the degloving skin, reduce the damage of the donor area.

Fast finite Hilbert transform via DE quadrature scheme.

PURPOSE: The finite Hilbert transform (FHT) or inverse finite Hilbert transform (IFHT) is recently found to have some important applications in computerized tomography (CT) arena, where they are used to filter the derivatives of back-projected data in the chord-line based CT reconstruction algorithms. In this paper, we implemented, improved and validated a fast numerical solution to the FHT via a double exponential (DE) integration scheme. A same strategy can be used to compute IFHT. METHODS: To overcome the underflow of floating-point numbers, we first determined the range of variable transformation from the minimum positive value of single or double precision floating point number, the integration step can be further determined by the range of variable transformation and the integration level. Two functions with their known analytical FHTs are used to validate the implementation of the FHT via DE scheme. The surface map and 2D contour of the FHT transformation error with respect to integration level and the range of the variable transformation are used to numerically determine the optimal numbers for a fast FHT. RESULTS: Given a specific precision, the lowest integration level and the optimal range of variable transformation, which are used to transform a signal with a certain degree of fluctuation, can be numerically determined by the surface map and 2D contour of the standard deviation of transformation error. These two numbers can then be taken to efficiently compute the FHT for other signals with the same or less degree of fluctuation. CONCLUSIONS: The FHT via DE scheme and the numerical method to determine the integration level and the range of transformation can be used for fast FHT in certain applications, such as data filtering in chord-line based CT reconstruction algorithms.

Single anterior approach for cervical spine fractures at C5-T1 complicating ankylosing spondylitis.

OBJECTIVES: To evaluate the outcomes of anterior approach for cervical spine fractures at C5-T1 in patients with ankylosing spondylitis (AS) and study the problems encountered in diagnosis and treatment. PATIENTS AND METHODS: Ten patients with AS (all males; mean age 43.7±9.4 years) underwent anterior surgeries to treat fractures at C5-T1. Skull tractions were performed on patients with fracture dislocation preoperatively. After operation, all the patients wore a cervical collar for 3 months. Plain radiographs at follow-up were reviewed. If bone fusion could not be confirmed on plain radiograph, CT scan was employed. The pre- and postoperative neurological statuses were evaluated according to the Frankel grading system. Problems encountered in diagnosis and treatments were analyzed. RESULTS: The mean follow-up was 41.2±22.7months. After operation, the displacements of fractures were significantly reduced(P<0.05). Bone fusions were observed in 9 patients at final follow-up. Frankel grades improved by 1.0±0.7 grade (P>0.05). Posterior complications occurred in four patients, including implants failure (n=1), subsidence of cage (n=1), hoarse voice (n=1) and pneumonias (n=2). The patient with implants failure required revision surgery and anterior-posterior fixation. Patient with subsidence of the titanium cage achieved bone fusion with prolonged cervical collar immobilization. CONCLUSION: The diagnosis and treatment of cervical spine fractures at C5-T1 in AS patients are challenging, with high risk of neurological compromise and postoperative complications. The single anterior approach followed by postoperative immobilization with a cervical collar can yield acceptable results if the cases are properly selected.

[Repair of wounds with Achilles tendon exposure].

OBJECTIVE: To investigate the application and clinical result of flap in the repair of wounds with Achilles tendon exposure. METHODS: Between May 2006 and May 2010, 21 patients with Achilles tendon skin defects were treated with microsurgical reconstruction. There were 15 males and 6 females, aged 7-63 years with a median of 34 years. The defect causes included sport injury in 4 cases, wheel twist injury in 7 cases, crush injury in 5 cases, chronic ulcer in 3 cases, and Achilles tendon lengthening in 2 cases. The areas of wounds with Achilles tendon exposure ranged from 2 cm x 2 cm to 10 cm x 8 cm. After debridement, wounds were repaired with the medial malleolus fasciocutaneous flap (5 cases), sural neurocutaneous vascular flap (8 cases), foot lateral flap (2 cases), foot medial flap (2 cases), and peroneal artery perforator flap (4 cases). The size of the flaps ranged from 3 cm x 3 cm to 12 cm x 10 cm. The donor sites were either sutured directly or covered with intermediate split thickness skin grafts. The Achilles tendon rupture was sutured directly (2 cases) or reconstructed by the way of Abraham (2 cases). RESULTS: All flaps survived and wounds healed by first intention except 2 flaps with edge necrosis. Twenty-one patients were followed up 6-18 months (mean, 12 months). The flaps had good appearance and texture without abrasion or ulceration. The walking pattern was normal, and the two point discrimination was 10-20 mm with an average of 14 mm. The American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale assessment revealed that 10 patients had an excellent result, 7 had a good result, 3 had a fair result, and 1 had a poor result with an excellent and good rate of 81.0%. Fourteen cases could lift the heels with power; 5 cases could lift the heels without power slightly; and 2 cases could not lift the heels. CONCLUSION: The wounds with Achilles tendon exposure should be repaired as soon as possible by appropriate flap according to the condition of wound.

[Application of modified superficial peroneal neuro-fasciocutaneous flap in repairing soft tissue defect of forefoot].

OBJECTIVE: To investigate the operative procedures and clinical outcomes of the modified superficial peroneal neuro-fasciocutaneous flap in repairing soft tissue defect of forefoot. METHODS: From May 2006 to May 2009, 5 male patients (aged 40-63 years) with soft tissue defect of forefoot were treated with the modified superficial peroneal neuro-fasciocutaneous flap. Tendons and bones were exposed in all cases. Defect was caused by object crash (4 cases) and traffic accident (1 case). The sizes of soft tissue defects of forefoot were 4 cm x 2 cm-8 cm x 4 cm. Rotating point of the modified superficial peroneal neuro-fasciocutaneous flap pedicled with the peripheral vessels network of ankle joint was at the level of tibiotalar joint. The flaps ranging from 5 cm x 4 cm to 10 cm x 6 cm were adopted to repair soft tissue defects of forefoot. The donor sites were either sutured directly or covered with intermediate split thickness skin grafts. RESULTS: All flaps survived and all wounds healed by first intention. Skin graft at donor site survived completely in all cases. All patients were followed up 6-18 months (mean 11 months). The appearance, texture, and function of the flap were satisfactory. There was a protective sensibility in all flaps without abrasion or ulceration, and the two-point discrimination of the flaps was 10-13 mm. The walking pattern was normal. No obvious discomfort was observed at the skin-graft donor sites. CONCLUSION: With reliable blood supply, no sacrifice of vascular trunks, favorable texture, and thickness, the modified superficial peroneal neuro-fasciocutaneous flap pedicled with the peripheral vessels network of ankle joint is useful to repair skin soft tissue defect of the forefoot.