Metal trabecular bone reconstruction system better improves clinical efficacy and biomechanical repair of osteonecrosis of the femoral head than free vascularized fibular graft: A case-control study.

In this study, we aim to compare and analyze the biomechanical repair and clinical efficacy of osteonecrosis of the femoral head (ONFH) with the use of metal trabecular bone reconstruction system and free vascularized fibular graft. The study enrolled 66 adult patients from medical records of nontraumatic ARCO 2A-3B stage ONFH. A simple ONFH model without surgical treatment was established in 13 cases, 29 cases were treated with metal trabecular bone reconstruction system, and 24 cases were treated with free vascularized fibular graft. Computer-recognized and extracted femur outlines were imported, and three-dimensional reconstructions were performed. The stress concentration and stress peak value were analyzed, and the Harris score, visual analog scale pain score, and operation status of the above patients were compared. Finally, quality of life assessment was performed using SF-36 scale. Metal trabecular bone reconstruction system provided less operation time, blood loss, and the total length of postoperative hospital stay than free vascularized fibular graft. Metal trabecular bone reconstruction system promoted bone reconstruction, increased bone mineral density and Harris score. The total clinical effective rate of young patients (20-40 years) was higher than that of older patients (41-60 years). Metal trabecular bone reconstruction system provided higher physical component summary, mental component summary, and role/social component summary than free vascularized fibular graft. This study demonstrates that both metal trabecular bone reconstruction system and free vascularized fibular graft can prevent or delay the progression of ONFH, while metal trabecular bone reconstruction system is a better choice because of better short-term clinical efficacy.

Role of C16, angiopoietin-1 and regeneration gene protein 2 in attenuating inflammation in an experimental rat model of autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits. Our results demonstrated that triple combination therapy was more efficient than the monotherapy in EAE treatment. The triple therapy significantly delayed the onset of motor symptoms, reduced disease severity, attenuated inflammatory cell infiltration and suppressed the secretion of proinflammatory cytokines. Additionally, treatment increased anti-inflammatory cytokines expression, inhibited reactive astrocytes proliferation, reduced demyelination and axonal loss, and finally reduced the neural death. Specifically, Reg-2 administration rescued oligodendrocytes and neuronal axons mainly by direct neurotrophic effects, while C16+Ang-1 (C+A) mainly improved the inflammatory milieu. In conclusion, our study suggests a possible synergistic effect through targeting a variety of pathways in relieving the clinical symptoms of inflammation in acute EAE model. Therefore, using molecules that target different molecular pathways can be beneficial for exploring novel therapeutic approaches for MS treatment.

[Lumbar plexus block combined with general anesthesia in treating postoperative delirium of hip fracture in elderly patients].

OBJECTIVE: To explore lumbar plexus nerve block combined with general anesthesia in elderly patients undergoing hip operation could improve analgesia effect, reduce consumption of analgesics, prevent inflammatory reaction, and avoid postoperative delirium(POD). METHODS: Totally 200 elderly patients underwent hip fracture surgery from February 2020 to September 2021 were selected and were divided into observation group and control group according to different anesthesia methods. There were 97 patients in observation group including 66 males and 33 females; aged (70.23±6.60) years old;body mass index (BMI) was (23.13±1.94) kg·m-2;19 patients with hemi arthroplasty, 46 patients with total hip arthroplasty, and 32 patients with femur intertrochanteric fixation;treated with lumbar plexus block combined with general anesthesia. There were 94 patients in control group, including 66 males and 33 females;aged (68.80±6.24) years old;BMI was (22.88±1.85) kg·m-2;14 patients with hemi arthroplasty, 39 patients with total hip arthroplasty, and 41 patients with femur intertrochanteric fixation;treated with only general anesthesia. Nine patients were separated due to the change of surgical protocol or chronic disease. The incidence of POD at 1, 2 and 3 days after surgery, mini-mental state examination (MMSE) score, visual analogue scale (VAS) in resting state, serum inflammatory factors levels [such as C-reactive protein(CRP), interleukin-1ß(IL-1ß), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] at 1 d before operation, 1 and 6 h after surgery, consumption of sufentanil between two groups were compared. RESULTS: The incidences of POD in observation group were lower than control group at 1, 2 and 3 days of operation (P<0.05), MMSE score in observation group was higher than that of control group (P<0.05), VAS in observation group was lower than that of control group (P<0.01). The incidences of POD decreased and MMSE score were increaed in both groups day by day (P<0.01). The levels of CRP, IL-1ß, IL-6 and TNF-α in observation group were lower than that of control group at 1 h after operation (P<0.01). The levels of CRP, IL-6 and TNF-α in observation group were lower than that of control group at 6 h after operation (P<0.01), while no statisitical difference in IL-1ß between two groups(P>0.05). The consumption of sufentanil in observation group was lower than that of control group (P<0.01). CONCLUSION: Compared with general anesthesia, lumbar plexus nerve block combined with general anesthesia for the operations of hip fracture in elderly patients has better analgesic effect, has advantages of slight inflammatory reaction, and could decrease consumption of opioid and incidence of POD.

A sophisticated fracture classification system of the proximal femur trochanteric region (AO/OTA-31A) based on 3D-CT images.

Objective: Fracture classification evolves dynamically with new and enhanced imaging modalities. This paper aims to introduce a novel hypothesis of a sophisticated fracture classification system for the proximal femur trochanteric region (AO/OTA-31A) based on 3D-CT images and accommodate the clinical requirement of the worldwide outbreak of geriatric hip fractures with large amounts of surgical operations. Methods: In the current practice of widely preoperative 3D-CT application and cephalomedullary nailing, we attempt to propose a new comprehensive classification system to describe the fracture characteristics in a more detailed and sophisticated architecture, and pay the most important concern to the parameters that contribute to fracture stability reconstruction in osteosynthesis. Results: The new four-by-four comprehensive classification system, followed the structure of the AO/OTA system, incorporates many fracture characteristics as dividing indexes into multiple grade levels, such as fracture line direction, the number of fragments, the lesser trochanter fragment and its distal extension (>2 cm), the posterior coronal fragment and its anterior expansion (to the entry portal of head-neck implant at the lateral cortex), the lateral wall and anterior cortex fracture, and the anteromedial inferior corner comminution. From a panoramic perspective, there are four types and each type has four subtypes. A1 is simple two-part fractures (20%), A2 is characterized by lesser trochanter fragment and posterior coronal fractures (62.5%), A3 is reverse obliquity and transverse fractures with complete lateral wall broken (15.5%), and A4 is medial wall comminution which further lacks anteromedial cortex transmission of compression force (2%). For subtypes, A2.2 is with a banana-like posterior coronal fragment, A2.4 is with distal cortex extension >2 cm of the lesser trochanter and anterior expansion of the posterior coronal fragment(s) to the entry portal of head-neck implants, A3.4 is a primary pantrochanteric fracture, and A4.4 is a concomitant ipsilateral segmental fracture of the neck and trochanter region. Conclusion: Classification represents diversity under consistency. The four-by-four sophisticated classification system delineates fracture characteristics in more detail. It is applicable in the time of rapid outbreak of trochanteric fractures in the older population, the large amounts of surgical operations, and incorporates various rare and/or more complicated subtypes which is unclassifiable before.

Author Correction: Intravenous C16 and angiopoietin-1 improve the efficacy of placenta-derived mesenchymal stem cell therapy for EAE.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Angiopoietin-1 and ανß3 integrin peptide promote the therapeutic effects of L-serine in an amyotrophic lateral sclerosis/Parkinsonism dementia complex model.

Amyotrophic lateral sclerosis (ALS) is an adult disorder of neurodegeneration that manifests as the destruction of upper and lower motor neurons. Beta-N-methylamino-L-alanine (L-BMAA), an amino acid not present in proteins, was found to cause intraneuronal protein misfolding and to induce ALS/Parkinsonism dementia complex (PDC), which presents symptoms analogous to those of Alzheimer's-like dementia and Parkinsonism. L-serine suppresses the erroneous incorporation of L-BMAA into proteins in the human nervous system. In this study, angiopoietin-1, an endothelial growth factor crucial for vascular development and angiogenesis, and the integrin αvß3 binding peptide C16, which inhibits inflammatory cell infiltration, were utilized to improve the local microenvironment within the central nervous system of an ALS/PDC rodent model by minimizing inflammation. Our results revealed that L-serine application yielded better effects than C16+ angiopoietin-1 treatment alone for alleviating apoptotic and autophagic changes and improving cognition and electrophysiological dysfunction, but not for improving the inflammatory micro-environment in the central nerve system, while further advances in attenuating the functional disability and pathological impairment induced by L-BMAA could be achieved by co-treatment with C16 and angiopoietin-1 in addition to L-serine. Therefore, C16+ angiopoietin-1 could be beneficial as a supplement to promote the effects of L-serine treatment.

Intravenous C16 and angiopoietin-1 improve the efficacy of placenta-derived mesenchymal stem cell therapy for EAE.

The placenta has emerged as an attractive source of mesenchymal stem cells (MSCs) because of the absence of ethical issues, non-invasive access, and abundant yield. However, inflammatory cell invasion into grafts negatively impacts the survival and efficacy of transplanted cells. Previous studies have shown that synthetic C16 peptide can competitively block the transmigration of leukocytes into the central nerve system, while angiopoietin-1 (Ang-1) can inhibit inflammation-induced blood vessel leakage and inflammatory cell infiltration in rats with experimental allergic encephalomyelitis (EAE). In this study, we investigated the effects of intravenous administration of C16 and Ang-1 on the efficacy of placenta-derived MSC (PMSC) transplantation in a rat model of EAE. We found that, compared with PMSCs alone, treatment with PMSCs along with intravenously administered C16 and Ang-1 was more effective at ameliorating demyelination/neuronal loss and neurological dysfunction, reducing inflammatory cell infiltration, perivascular edema, and reactive astrogliosis (p < 0.05). Mechanistic studies revealed that intravenous C16 and Ang-1 increased PMSC engraftment in the central nervous system and promoted expression of the neurotropic proteins brain-derived neurotrophic factor, growth-associated protein 43, and p75 neurotrophin receptor as well as the neuronal-glial lineage markers neurofilament protein 200 and myelin basic protein in the engrafted PMSCs.

[Treatment of multi-segment fracture of complex femoral shaft with instrument-assisted reduction combined with intramedullary interlocking nail fixation].

OBJECTIVE: To investigate the effect of minimally invasive mini-incision and instrumented reduction combined with interlocking intramedullary nailing in the treatment of patients with multi-segment fracture of complex femoral shaft. METHODS: From January 2013 to January 2016, 32 patients with multiple fractures segments of femoral shaft were treated with instrumentation-assisted reduction combined with interlocking intramedullary nailing, including 22 males and 10 females with an average age of 45 years old ranging 17 to 68 years old. The time from injured to operation was 5 to 10 days with an average of 7 days. After admission, routine tibial tubercle or supracondylar bone traction was performed. The patient's general condition was evaluated, the operation time and intraoperative blood loss were recorded. According to Thorsen femoral fracture morphology evaluation criteria and Hohl knee function evaluation of postoperative efficacy, postoperative fracture healing, complications and postoperative recovery of limb function were observed. RESULTS: All patients were followed up for 6 to 24 months with an average of 12 months. The operative time ranged from 48 to 76 minutes with an average of 67 min. The intraoperative blood loss was 150 to 400 ml with an average of 220 ml. The surgical incisions all achieved grade A healing. The fractures reached the clinical standard of healing. The fracture healing time ranged from 4.2 to 10.8 months with an average of 5.7 months. There were no nonunion, incision infection and internal fixation fracture, failure and other complications. According to Thorsen femoral fracture morphology evaluation criteria, the result was excellent in 28 cases, good in 3 cases, fair in 1 case. According to Hohl knee function evaluation criteria, the result was excellent in 30 cases, good in 2 cases. CONCLUSIONS: Instrument-assisted reduction combined with interlocking intramedullary nail fixation is a safe and effective method for the treatment of complex femoral shaft fractures. It has advantages of small trauma, fixed fixation, quick recovery, early postoperative functional exercise.

Angiopoietin-1 and C16 Peptide Attenuate Vascular and Inflammatory Responses in Experimental Allergic Encephalomyelitis.

Breakdown of normal blood-brain barrier function and accompanying vascular leakage are fundamental stages in the onset of multiple sclerosis and its animal counterpart, experimental allergic encephalomyelitis. In the present study, angiopoietin-1, an endothelial growth factor well known for its role in establishing and maintaining vascular integrity, and C16, a peptide that competitively binds to integrin αvß3 expressed on endothelial cells, were used to treat acute experimental allergic encephalomyelitis in Lewis rats. Angiopoietin-1 was more effective than C16 for reducing inflammation-induced vascular leakage. Moreover, treatment with a combination of angiopoietin-1 and C16 resulted in greater effects, not only in alleviating inflammation and reducing axonal loss/demyelination but also in down-regulating pro-inflammatory cytokine expression and improving electrophysiological dysfunction, than treatment with either angiopoietin-1 or C16 alone. Different protective effects were observed with angiopoietin-1 and C16 treatment suggesting that these proteins target specific receptors to act through different pathways. Furthermore, angiopoietin-1 and C16 may form the basis of a promising therapeutic strategy for experimental allergic encephalomyelitis and multiple sclerosis.

Reg-2, A Downstream Signaling Protein in the Ciliary Neurotrophic Factor Survival Pathway, Alleviates Experimental Autoimmune Encephalomyelitis.

Ciliary neurotrophic factor (CNTF), originally described as a neurocytokine that could support the survival of neurons, has been recently found to alleviate demyelination, prevent axon loss, and improve functional recovery in a rat model of acute experimental autoimmune encephalomyelitis (EAE). However, poor penetration into the brain parenchyma and unfavorable side effects limit the utility of CNTF. Here, we evaluated the therapeutic potential of a protein downstream of CNTF, regeneration gene protein 2 (Reg-2). Using multiple morphological, molecular biology, and electrophysiological methods to assess neuroinflammation, axonal loss, demyelination, and functional impairment, we observed that Reg-2 and CNTF exert similar effects in the acute phase of EAE. Both treatments attenuated axonal loss and demyelination, improved neuronal survival, and produced functional improvement. With a smaller molecular weight and improved penetration into the brain parenchyma, Reg-2 may be a useful substitute for CNTF therapy in EAE and multiple sclerosis (MS).

Intravenous injection of l-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson-dementia complex.

Non-protein amino acid beta-N-methylamino-l-alanine (l-BMAA) is a neurotoxin that was associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinson-Dementia Complex (ALS/PDC) in Guam. This neurotoxin has been implicated as a potential environmental factor in amyotrophic lateral sclerosis, Alzheimer's disease and other neurodegenerative diseases, and was found to accumulate in brain tissues of ALS/PDC patients. It is extremely important to establish a reliable animal model that has the comprehensive characteristics of ALS/PDC for studying mechanisms underlying neurodegeneration, and exploring effective therapies. However, very few good animal models that mimic ALS/PDC have been established. In this study, an ideal rat model that mimicked most characteristics of ALS/PDC was established by administering continuous intravenous (i.v.) injections of neurotoxic l-BMAA. Based on the data obtained, it was demonstrated that continuous i.v. injections of l-BMAA induced mitochondrial morphology and structural changes, astrogliosis, motor neuronal death, and other relative functional changes, which led to the overexpression of pro-inflammatory cytokines cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α), and resulted in the upregulation of glycogen synthase kinase-3 (GSK3), downregulation of astrocytic glutamate transporter-1 (GLT-1), accumulation of microtubule-associated protein tau and cytosolic aggregates of TAR DNA-binding protein-43 (TDP-43) in degenerating motor neurons. These results suggest that this model could be used as a useful tool for the mechanistic and therapeutic study of ALS/PDC.

[Subtype classification of Garden III femoral neck fractures in the elderly based on frontal Garden index and its clinical significance].

OBJECTIVE: To retrospectively study postoperative Garden III femoral neck fractures in the elderly so as to explore the different degree of displacement of Garden III femoral neck fracture, and discuss the basis and clinical significance of the subtype classification. METHODS: A total of 492 patients with complete clinical data out of the 1397 patients with femoral neck fractures treated by closed reduction and internal fixation with cannulated compression screws from September 2005 to September 2010 were included in the study. Each patient's frontal Garden Index was measured. On the basis of the frontal Garden Index, these cases were divided into three types:type A, which frontal Garden Index was more than or equal to 140°, included 53 males and 84 females with an average age of(65.3±7.2) years old ranging from 60 to 75 years old; type B, more than 120°and less than 140°, included 79 males and 172 females with an average age of (67.5±3.6) years old;and type C, less than or equal to 120°, included 38 males and 66 with an average age of(68.6±5.7) years old. Aspects were followed up including complications, consequences and hip joint function. The fracture healing and femoral head necrosis were compared among three types. RESULTS: Operative incision of 492 cases was primary healing, and no infection and other complications occurred. All patients were followed up from 2 to 10 years with an average of 6.3 years, the healing of femoral neck fracture occurred in 432 cases, and the total union rate was 87.8%. Femoral head necrosis occurred in 83 cases, and the total necrosis rate of femoral head was 16.9%. The nonunion rate of type A was 6.6%, type B was 13.5%, and type C was 16.3%, there were significant differences among three types(χ²2AB=4.377, P=0.036;χ²2AC=5.872, P=0.015;χ²2BC=0.469, PBC=0.494). The necrosis rate of femoral head of group A was 8.8%, group B was 16.7%, and group C was 27.9%, there were significant differences among three groups(χ²2AB=4.704, P=0.030;χ²2AC=15.317, P=0.000;χ²2BC=5.715, P=0.017). CONCLUSIONS: It is different for the degree of displacement of Garden III femoral neck fracture in the elderly. Based on frontal Garden Index to differentiate degree of fracture displacement, Garden III femoral neck fracture would be divided into A, B and C subtypes. The prognosis of Garden III femoral neck fracture in the elderly is negatively related to its degree of displacement, which has clinical significance to make treatment plan for Garden III femoral neck fracture in the elderly.

[Application of double joystick technique in reduction-internal fixation for femoral shaft fracture in adults].

OBJECTIVE: To study the applied value of double joystick technique in reduction-internal fixation for femoral shaft fracture in adults. METHODS: Thirty-four patients (24 males and 10 females) with femoral shaft fractures were treated with reduction assisted by double joystick technique and internal fixation with interlocking intramedullary nail from September 2010 to June 2013. The average age of the patients was 41 years old, ranged from 17 to 65 years old. The duration of the disease course ranged from 3 to 7 days, with a mean of 5 days. The fractures belonged to AO types 32A (5 cases), 32B (20 cases) and 32C (9 cases) and located in left femur for 18 patients and right femur for 16 patients. The patients were followed up, and fracture healing and complications were observed. The curative effect were evaluated according to Thorsen femur fracture evaluation standard. RESULTS: The operative time ranged from 40 to 110 min (mean 75 min) and intraoperative blood loss ranged from 200 to 300 ml (mean 250 ml). All the patients obtained a good fracture reduction and were followed up for 12 to 24 months (mean 18 months) after the surgery. All the fractures united between 4 and 8 months with a mean of 5 months. No complications such as breakage of nail, infection, osteofascial compartment syndrome, refracture and fracture malunion were found. According to Thorsen femur fracture evaluation standard, 30 patients obtained an excellent result, 3 good and 1 fair. CONCLUSION: In surgery of reduction-internal fixation for femoral shaft fracture in adults, the use of double joystick technique obtains good reduction result, short operative time, less injury, high healing rate of bone fractures, less complications and good limbs function, so it is worthy of popularizing in clinic.