Mitochondrial homeostasis regulation: A promising therapeutic target for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) or Lewy neurites (LNs) which consist of α-synuclein (α-syn) and a complex mix of other biomolecules. Mitochondrial dysfunction is widely believed to play an essential role in the pathogenesis of PD and other related neurodegenerative diseases. But mitochondrial dysfunction is subject to complex genetic regulation. There is increasing evidence that PD-related genes directly or indirectly affect mitochondrial integrity. Therefore, targeted regulation of mitochondrial function has great clinical application prospects in the treatment of PD. However, lots of PD drugs targeting mitochondria have been developed but their clinical therapeutic effects are not ideal. This review aims to reveal the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases based on the mitochondrial structure and function, which may highlight potential interventions and therapeutic targets for the development of PD drugs to recover mitochondrial dysfunction in neurodegenerative diseases.

[Comparison of effect between internal fixation and total hip replacement in the treatment of displaced femoral neck fracture in middle age patients].

OBJECTIVE: To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years. METHODS: From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups. RESULTS: All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05). CONCLUSION: Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.

[Review of closed reduction techniques for femoral neck fracture].

For patients with femoral neck fractures who plan to undergo internal fixation, satisfied alignment of fracture ends is an important prerequisite for internal fixation stability and fracture healing. There are many reports on the reduction methods of displaced femoral neck fractures, which can be summarized into three categories:First, the solely longitudinal traction of lower limbs, supplemented by other manipulations such as rotation and compression; Second, the resultant force formed by the longitudinal traction of lower limbs and the lateral traction;the third is accomplished by vertical traction in the axis of femur with hip joint flexed. Each reduction method has its own advantages, but no single method can be applied to all fracture displacement. In this paper, some classical reduction techniques in the literatures are briefly reviewed. It is hoped that clinicians will not be limited to a certain reduction method, they should analyze the injury mechanism and fracture displacement process according to the morphology features and flexibly select targeted reduction methods to improve the success rate of closed reduction of femoral neck fracture.

[Assessment of the local blood supply when femoral neck fracture occurs:advances in the anatomy research and its clinical application].

The stability of internal fixation of femoral neck fractures can be obtained through surgical techniques, the configuration of screws and bone grafting, etc. However, the blood supply injury caused by fractures could not be completely reversed by the current medical management. Hence, the comprehensive evaluation of the residual blood supply of the femoral neck, to perioperatively avoid further iatrogenic injury, has become a hotspot. The anatomy of the extraosseous blood supply of the femoral neck has been widely reported, while its clinical application mostly involved the assessment of the medial circumflex femoral artery and retinacular arteries. However, further studies are needed to explore the prognosis of patients with these artery injuries, with different degrees, caused by femoral neck fractures. Direct observations of nutrient foramina in vivo are not possible with current clinical technologies, but it is possible to make reasonable preoperative planning to avoid subsequent femoral head necrosis based on the distribution features of nutrient foramina. The anatomy and clinical application studies of the intraosseous blood supply focused on the junction area of the femoral head and neck to probe the mechanism of femoral head necrosis. Thus, the intraosseous blood supply of other regions in the femoral neck remains to be further investigated. In addition, a blood supply evaluation system based on a three-level structure, extraosseous blood vessels, nutrient foramina, and intraosseous vascular network, could be explored to assist in the treatment of femoral neck fractures.

Reoperation rate and implants' position variation features of displaced femoral neck fractures with sliding compression or length-stable fixation in young and middle-aged population.

INTRODUCTION: Sliding compression fixation and length-stable fixation are two basic internal fixation concepts in the treatment of displaced femoral neck fractures. In this study, we aimed to compare the reoperation rates for different methodologies of internal fixation for femoral neck fractures in young and middle-aged population. MATERIALS AND METHODS: This a retrospective study. A total of 215 patients with displaced femoral neck fractures treated with cannulated screw fixation were enrolled and divided into the sliding compression and length-stable groups according to the fixation pattern. The occurrence of and reason for revision surgery within one year were recorded. Forty-five patients with complete CT data (including CT scanning on the first postoperative day and at the last follow up) were selected from the total sample. A newly established computerized image processing method was used to evaluate variations in the spatial location of screws. RESULTS: The reoperation rate was significantly higher in the length-stable group (23.8%) than in the sliding compression group (7.3%). The rate of revision surgery due to nonunion was also higher in the length-stable group (11.4%) than in the sliding compression group (1.8%). However, no significant difference was observed in terms of joint penetration or soft tissue irritation. The sliding compression group (6.58 ± 3.18 mm) showed higher femoral neck shortening than length-stable group (4.16 ± 3.65 mm). When analyzing the spatial variations, a significantly greater screw withdrawal distance was observed in the sliding compression group than in the length-stable group, but with a smaller rotation angle. CONCLUSION: Length-stable internal fixation of displaced femoral neck fractures may lead to an increased reoperation rate in young and middle-aged population. TRIAL REGISTRATION: Name of the registry: Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2000032327. Trial registration date: 2020-4-26.

A quantitative study of bone defects in displaced femoral neck fractures based on virtual reduction techniques.

BACKGROUND: Bone defects in femoral neck fractures are strongly associated with the prognosis after internal fixation. However, qualitative analysis of bone defects in femoral neck fractures has already been performed, quantitative studies have not been reported. In this study, we aimed to systematically analyse the morphological characteristics of bone defects in patients with femoral neck fractures using computed tomography (CT) images combined with computer image analysis techniques. METHODS: Four hundred and sixty-nine patients with femoral neck fractures from January 2014 to December 2018 at two grade A tertiary hospitals were included. Models were created in Mimics software based on CT images collected within 1 week after injury and then imported into 3-matic software for virtual reduction. The volume of the bone defect (VBD), maximum defect thickness (MDT), extent of the bone defect region (EBDR) , main defect quadrant (MDQ), collapse type and fracture classification were calculated and recorded. RESULTS: The EBDR, collapse type and MDT all had a significant positive effect on the VBD (P <0.05), with a more significant effect at higher quantiles. Age also had a significant positive effect on the VBD (P < 0.05), but its effect was more pronounced at lower quantiles. Compared to non-subcapital fractures, subcapital fractures had a positive effect on the VBD only at the 50 and 75% quantiles (P < 0.01). The female sex had a significant negative effect on the VBD compared to the male sex (P < 0.05). CONCLUSION: This study established a reliable computer image processing method for quantitative analysis of the VBD in femoral neck fractures and revealed that all patients with femoral neck fractures had bone defects, which can occur at any part of the femoral neck. The EBDR, MDT, collapse type, and patient age and sex were all important risk factors for the extent of the defect and should be taken into account in surgical planning.

A retrospective cohort study on prevalence of postoperative complications in comminuted patellar fractures: comparisons among stabilized with Cannulated-Screw, Kirschner-Wire, or Ring-Pin Tension Bands.

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.

Metformin Prevents Nonunion after Three-Cannulated-Screw Fixation in Displaced Femoral Neck Fractures: A Retrospective Study.

Patients aged from 40 to 60 with displaced fractures of the femoral neck (Garden III or IV) who received fixation with three cannulated screws from January 2005 to December 2012 were evaluated retrospectively for the development of nonunion. Plasma HbA1C, a marker for long-term plasma glucose level, anti-T2DM medication, and other potential risk factors were recorded for the purpose of this study. There were no differences between the union and nonunion groups with respect to age, gender, Garden classification, Pauwel's angle, reduction quality, and T2DM presence. There were significant differences in reduction quality and preoperative plasma HbA1C level between patients with and those without union. The odds ratio (OR) for fracture nonunion was 2.659 (95% confidence interval [CI], 1.530-4.620) in subjects with anatomical reduction compared with those without anatomical reduction, 4.797 (95% CI, 1.371-16.778), in subjects with poor blood glucose control (HbA1C > 10%). The metformin usage showed a preventive effect on nonunion development (OR: 0.193 and CI: 0.060-0.616). The nonunion rate of metformin group (6.7%, 6/89) was even much lower than that of patients without T2DM (17.4%, 80/460).

Intermittent internal fixation with a locking plate to preserve epiphyseal growth function during limb-salvage surgery in a child with osteosarcoma of the distal femur: a case report.

Limb shortening is a problem associated with surgery for osteosarcoma of the lower extremity in adolescents, as the tumors frequently occur near the epiphysis. Herein we report the use of a less invasive stabilization system (LISS) and an intermittent fixation method to preserve the growth function of epiphysis in an 11-year-old patient with an osteosarcoma of the distal femur.The 11-year-old male presented with left knee enlargement and pain for 2 weeks, and magnetic resonance imaging (MRI) and biopsy were consistent with osteosarcoma of the left distal femur. After preoperative chemotherapy, en bloc tumor resection was performed with margins based on MRI findings preserving the epiphyseal growth plate, the tumor cavity was filled with inactivated bone and bone cement, and a LISS was used to stabilize the femur. Aggressive postoperative chemotherapy was given. Approximately 105 weeks after surgery radiography showed that the distal end of the plate had moved superior to the epiphysis along with bone growth. Locking screws were placed in the distal part of the LISS plate to stabilize the re-implanted bone, and external fixation was not needed.The patient was able to walk with the crutches 1 week postoperatively, and bear weight on the extremity 6 weeks postoperatively. At 6 years after surgery, the patient's height had increased 52 cm, shortening of the affected limb was only 1 cm, and the circumference of the affected limb was 2 cm smaller than that of the contralateral limb. There was no significant discomfort in the affected limb, and there was no gait abnormality. The patient could jump and run, and could participate in sports including basketball and badminton to the same degree as his peers.In summary, the novel method of bone reconstruction and fixation provided good results in a child with an osteosarcoma of the distal femur. This fixation method preserves the osteogenic function of the epiphysis and restored bone integrity simultaneously, and provides good functional recovery.

Silencing of Glucose Transporter Protein-1 by RNA Interference Inhibits Human Osteosarcoma Mg63 Cells Growth in vivo.

While knock-down of glucose transporter protein 1 (GLUT-1) inhibited various human cancer cell growth in vitro and in vivo, including osteosarcoma cell growth in vitro, there has been no report on whether knock-down of GLUT-1 by siRNA may inhibit osteosarcoma cell growth in vivo. We hypothesized that siRNA may inhibit osteosarcoma cell growth in vivo. We introduced siRNA-GLUT-1 by lentivirus into MG63 osteosarcoma cells which were xenograted into nude mice. Immunohistochemical staining, Western blot and reverse transcriptase quantitative (RT-qPCR) were used to determine GLUT-1 protein and mRNA expression of the tumor cells. The results showed the tumor volume of GLUT-1-siRNA-MG63 cells xenorafted nude mice was significantly less than that of siGFP-MG63 or MG63 cells xenografted nude mice (P < 0.05), suggesting that silencing of GLUT-1 inhibited tumor formation and growth of osteosarcoma cells in vivo. Our findings suggest that the lentiviral-mediated siRNA interference against GLUT-1 may be a valuable tool for gene therapy for osteosarcoma.

Functional outcomes and quality of life in patients with osteosarcoma treated with amputation versus limb-salvage surgery: a systematic review and meta-analysis.

INTRODUCTION: To perform a meta-analysis for comparing the functional outcomes and quality of life (QOL) of osteosarcoma patients receiving amputation or limb-salvage surgeries. MATERIALS AND METHODS: A search was conducted of the Medline, Cochrane, EMBASE, and Google Scholar on September 30, 2013. Studies were included in the analysis if there were patients who underwent amputation and limb-salvage surgery for osteosarcoma or Ewing's sarcoma, and for whom postoperative functional outcomes and QOL were evaluated. Outcomes were compared between participants who underwent limb-salvage operation and those who underwent amputation. The methodological quality of non-randomized comparative studies was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 121 studies were identified and 6 were included in the meta-analysis. Quality assessment indicated that all six studies were of high quality. The mean age of the participants ranged from 17 to 37 years, and among them 118 underwent amputations and 138 underwent limb-salvage procedures. The mean length of follow-up ranged from 28 to 145 months. The meta-analysis indicated that functional outcomes and QOL were similar between patients who underwent amputation and those who underwent a limb-salvage procedure. CONCLUSIONS: This meta-analysis including six high-quality studies indicates that amputation and limb-salvage surgery provide similar functional outcomes and quality of life for patients with osteosarcomas.

Distally based perforator propeller sural flap for foot and ankle reconstruction: a modified flap dissection technique.

BACKGROUND: Distally based perforator propeller sural flaps that pedicled on an isolated perforator from the peroneal artery or posterior tibial artery are a versatile local reconstructive option for defects of the foot and ankle region. However, flap venous congestion is yet a difficult problem after operation. We hypothesize that containing some adipofascial tissues around the axial perforator can preserve some tiny venous return routes, improve venous drainage, and ultimately enhance flap safety in distally based sural flaps. METHODS: A prospective case series of 12 patients undergoing distally based perforator sural flaps for foot and ankle coverage were included in this study from January 2008 to December 2010. There were 7 posterior tibial artery perforator flaps from the posteromedial sural region and 5 peroneal artery perforator flaps from the posterolateral sural region. After identifying the proper viable perforator during operation as the pivot point, the whole flap was designed in an eccentric propeller shape. The proximal larger blade was a fasciocutaneous flap, whereas the distal smaller blade was a subdermal vascular plexus flap, preserving at least a quarter area of adipofascial tissue intact around the perforator. Postoperatively, flap swelling was classified into a 5-grade assessment scale. Flap survival, complications, and patient functional recovery were evaluated. RESULTS: The proximal fasciocutaneous flap measured 4 × 8 to 6 × 18 cm (mean, 57.8 cm), and the distal subdermal cutaneous flap measured 2 × 2 to 4 × 4 cm (mean, 9.2 cm). The flaps were rotated 160 to 180 degrees. Postoperatively, flap swelling was noted under grade 2 in 9 cases, grade 3 in 2, and grade 4 in 1 with some distal superficial skin necrosis, which occurred in the largest flap in our series. All flaps survived uneventfully. After a mean of 13 months of follow-up, the wounds were cured successfully. All patients recovered walking and shoe wearing function. CONCLUSION: Keeping a quadrant adipofascial tissue around the distal pivot perforator to form a perforator-adipofascial-pedicle can preserve more venous return routes and relieve flap swelling. This technique should be recommended in distally perforator-pedicled propeller flaps because it enhances flap safety yet does not increase the difficulty of 180-degree rotation.

Posterior coronal plating of bicondylar tibial plateau fractures through posteromedial and anterolateral approaches in a healthy floating supine position.

Bicondylar tibial plateau fractures pose a significant challenge for treating surgeons. If the articular surface of the medial plateau has a second split component in the posterior coronal plane, it is difficult to get direct visualization and ensure plate fixation when the patient is in the supine position. Using a technique in which a single preparation and draping of both legs is needed, patients were operated on using a healthy floating supine position maneuver through dual posteromedial and anterolateral incisions and triple plate fixations. By flexing and adducting the contralateral healthy hip over the injured leg, more lateral rotation of the fractured knee can be achieved, providing better access and visualization of the posterior medial plateau using a posteromedial gastrocnemius approach.

[Surgical treatment of flatfoot resulting from calcaneal fractures malunion].

OBJECTIVE: To explore the operative approach and efficacy of flatfoot after calcaneal fractures malunion. METHODS: A total of 116 flatfoot patients after old calcaneal fractures were treated from January 1998 to January 2008. There were 94 males and 22 females with an average age of 33.5 years old (range: 16 - 46). They included unilateral flatfoot after old calcaneal fractures (n = 110) and bilateral flatfoot after old calcaneal fractures (n = 6). The surgical treatments included open reduction, calcaneal osteotomy without subtalar fusion or a reconstruction of calcaneal thalamus and subtalar arthrodesis. RESULTS: A total of 101 patients were followed up for an average of 14 months (range: 12 - 24). No wound healing problem or infection was observed. Solid union was obtained without redislocation in all patients. The mean time of bone union was 12 weeks (range: 10 - 14). The mean time of complete weight loading was 13 weeks (range: 11 - 15 weeks). The height of foot arch increased from 4.2 mm ± 1.7 mm to 14.1 mm ± 4.1 mm (P < 0.05). Calcaneal inclination angle increased from 11.2° ± 2.5° to 19.1° ± 4.4° (P < 0.05). Bohler angle increased from 5.4° ± 3.5° to 25.8° ± 5.2° (P < 0.05). Meary angle recovered from 22.2° ± 4.4° to 5.1° ± 3.2° (P < 0.05). The mean AOFAS Ankle and Hindfoot score increased from 33.4 (range: 27 - 43) to 85.8 (range: 78 - 98). CONCLUSION: As to flatfoot after old calcaneal fractures, surgical treatment has a favorable efficacy. A customized operative approach may achieve a satisfactory outcome.

Inhibition of tumors cell growth in osteosarcoma-bearing SD rats through a combination of conventional and metronomic scheduling of neoadjuvant chemotherapy.

AIM: To investigate whether a combination of conventional and metronomic scheduling of chemotherapy could enhance and extend the effectiveness of chemotherapy against osteosarcoma. METHODS: A total of 110 osteosarcoma-bearing SD rats were randomly divided into four groups, three of which were given conventional, metronomic or combination scheduling of chemotherapy, and the remaining one served as a control. Tumor volumes were measured every week during the treatment period of 8 weeks. At the end of treatment, tumors were removed from the rats and weighed. Expression of VEGFA in tumors was determined using Western blot assays. RESULTS: As indicated by the tumor volume, conventional and metronomic schedules showed similar trends in tumor growth curves, and both of them lost their inhibitory effect in the sixth week, whereas the combination schedule maintained effectiveness until the end of treatment. Statistical significance with tumor volumes and weights was found among the groups (P<0.001), with combination scheduling being the most effective (P<0.001). Western blot indicated that all the therapy groups had significantly decreased expression of VEGFA (P<0.01), and the combination scheduling group had the lowest VEGFA expression. CONCLUSION: Combination of conventional and metronomic scheduling of chemotherapy could be a promising treatment for osteosarcoma. Antiangiogenesis contributed to the effect of combination scheduling.

[Surgical treatment of malunited or nonunited talus fractures].

OBJECTIVE: To explore the operative methods of malunited or nonunited talus fractures. METHODS: Twenty-two patients of malunions or nonunions after displaced talar fractures were treated from January 2000 to January 2008. There were 17 males and 5 females with an average age of 34 years (ranged from 15 to 52 years). According to classification of posttraumatic talar deformities (Zwipp 2003), there were 10 cases of type I (malunion and/or joint displacement), 8 cases of type II (nonunion with joint displacement), 4 cases of type III (type I/II with partial AVN). The surgical treatments included open reduction, osteotomy, correction and internal fixation with plate, screw or K-wire, or the ankle, subtalar arthrodesis. RESULTS: Seventeen patients were followed up for 14 months in average (ranged from 12 to 24 months). No wound healing problems or infections were observed. Solid union was obtained without redislocation in all patients. The mean time of bone union was 14 weeks (ranged from 12 to 18 weeks). The mean time of completely weight loading was 14 weeks (ranged from 12 to 18 weeks). The mean AOFAS ankle and hindfoot score increased from 35.4 (ranged from 28.0 to 41.0) to 86.6 (ranged from 78.0 to 98.0). CONCLUSIONS: As to posttraumatic talar deformities, surgical treatment can lead to a favorable outcome. According to concrete status of malunions or nonunions after displaced talar fractures, suitable surgical treatment should be applied to obtain satisfactory outcome.