[Molecular mechanism of residual lumbago and leg pain after transforaminal endoscopic treatment of lumbar disc herniation].

OBJECTIVE: To observe the residual of lumbago and leg pain with contained type （CT） and non-contained type （NCT） lumbar disc herniation （LDH） after transforaminal endoscopic treatment, and to explore the role of hypoxia-inducible factor-1α（HIF-1α） and transient receptor potential vanillate 1（TRPV1） pathway. METHODS: A total of 68 single-segment LDH patients were selected from July 2021 to October 2022, including 44 males and 24 females；aged 26 to 67 years old with an average of（43.63±11.94） years old；course of disease was 4 to 36 （18.91±10.34） months；body mass index was （24.45±4.00） kg·m-2；there were 7 cases of L3,4 segments, 32 cases of L4,5 segments, and 29 cases of L5S1 segments. All of them were performed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group（CT group） and non-contained group （NCT group） with 34 cases respectively according to the integrity of outer layer of fibrous annulus observed during operation. A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were selected as control group, including 12 males and 5 females；aged 21 to 65 years old with an average of （39.41±12.80） years old；body mass index was （24.86±4.11） kg·m-2. The relative mRNA expression quantity of HIF-1α, TRPV1 in nucleus pulposus were measured by quantitative real-time PCR. The contents of neurokinin 1 receptor （NK1R）, nerve growth factor （NGF）, vascular endothelial growth factor （VEGF） in nucleus pulposus and the serum substance P （SP） and calcitonin gene-related peptide （CGRP） were detected by enzyme linked immunosorbent assay （ELISA）. The threshold of lumbar tenderness was detected by a pressure pain meter. The degree of lumbago and lumbar function were evaluated by visual analog scale （VAS） and Oswestry disability index （ODI） separately. The residual rate of postoperative lumbago and leg pain was assessed. RESULTS: The mRNA relative expression quantity of HIF-1α and TRPV1, and the contents of NK1R, NGF and VEGF in nucleus pulposus, and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group（P<0.05）, and those in the CT group were higher than the control group（P<0.05）. At day 7 after surgery, the serum SP and CGRP levels, lumbago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery （P<0.05）, and those in the NCT group were higher than the CT group（P<0.05）, and the threshold of lumbar tenderness in the NCT group was lower than the CT group（P<0.05）. The differences of lumbago and leg pain VAS scores, lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group（P<0.05）. The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group（P<0.05）. CONCLUSION: HIF-1α and TRPV1 pathway promoted the excessive production of NGF, VEGF, NK1R in nucleus pulposus and serum neuropeptides SP and CGRP, which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Computational Biomechanical Analysis of Postoperative Calcaneal Fractures with Different Placement of the Sustentaculum Screw.

OBJECTIVE: To evaluate the computational biomechanical analysis of intra-articular calcaneal fractures with different fixation status of the sustentaculum plate screw, when the finite element modeling of calcaneal fractures were fixed by the lateral locking plate. METHODS: The normal right foot of a male (age: 36 years; height: 174 cm; body weight: 65 kg) was scanned by the CT scanner. As the computational biomechanical study, the three-dimensional finite element model of the simplified Sanders type-II calcaneal fracture was built. Fixation with the lateral calcaneal locking plate and screws was simulated using a finite element software package according to clinical operation. According to the different placement of the sustentaculum plate screw, the models were categorized as the accurate fixation group, marginal fixation group, and non-fixation group. The loading of 650 N with the vertical axial compression was applied to simulate the standing phase with single foot. The Von Mises stress distribution, maximal displacement, and contact area of the subtalar joint were analyzed among three groups. RESULTS: The pressure distribution of the subtalar joint facet was inhomogeneous. The stress concentration of the calcaneus was located at the medial zone of the posterior subtalar joint facet. The peak Von Mises stress distribution in three groups was similar at the subtalar joint facet of 4.9 MPa, 5.1 MPa, and 5.4 MPa. In the accurate fixation group, the contact area on the posterior articular facet was 277.1 mm2 ; the maximal displacement was 0.18 mm. The contact area of the marginal fixation group was 265.3 mm2 on the posterior facet, where the maximal displacement was 0.23 mm. In the non-fixation group, the contact area was 253.8 mm2 ; the maximal displacement was 0.25 mm. There was a slight change in the contact area of the subtalar joint and no prominent displacement of the calcaneus could be detected among the three groups. CONCLUSIONS: The biomechanical results, including the peak stress distribution, contact area, and maximal displacement of subtalar joint, were similar whether the screw is placed exactly within the sustentaculum tali or not, when the calcaneal fractures were fixed by the lateral locking plate. The sustentaculum plate screw had less effect on the biomechanical performance of the calcaneus.

Postoperative Evaluation of Reduction Loss in Proximal Humeral Fractures: A Comparison of Plain Radiographs and Computed Tomography.

OBJECTIVE: To compare postoperative CT images with plain radiographs for measuring prognostic factors of reduction loss of fractures of the proximal part of the humerus. METHODS: A total of 65 patients who sustained fractures of the proximal humerus treated with locking plates from June 2012 to October 2015 were retrospectively analyzed. There were 24 men and 41 women, with a mean age of 60.0 years (range, 22-76 years). According to the Neer classification system of proximal humeral fracture, there were 26 two-part, 27 three-part and 12 four-part fractures of the proximal part of the humerus, and all fractures were treated with open reduction and internal fixation (ORIF) using locked plating. All postoperative CT images and plain radiographs of the patients were obtained. Prognostic factors of the reduction loss were the change of neck shaft angle (NSA) and the change of humeral head height (HHH). The change of NSA and HHH were evaluated by the difference between postoperative initial and final follow-up measurement. Reduction loss was defined as the change ≥10° for NSA or ≥5 mm for HHH. The NSA and HHH were measured using plain radiographs and 3-D CT images, both initially and at final follow-up. The paired t-test was used for comparison of NSA, change of NSA, HHH, and change of HHH between two image modalities. The differences between two image modalities in the assessment of reduction loss were examined using the χ2 -test (McNemar test). Intraclass correlation coefficients (ICC) were used to assess the intra-observer and inter-observer reliability. RESULTS: 3-D CT images (ICC range, 0.834-0.967) were more reliable in all parameters when compared with plain radiographs (ICC range, 0.598-0.915). Significant differences were found between the two image modalities in all parameters (plain radiographs: initial NSA = 133.6° ± 3.8°, final NSA = 130.0° ± 1.9°, initial HHH = 17.9 ± 0.9 mm, final HHH = 15.8 ± 1.5 mm; 3-D CT: initial NSA = 131.4° ± 3.4°, final NSA = 128.8° ± 1.7°, initial HHH = 16.8 ± 1.2 mm, final HHH = 14.5 ± 1.1 mm; all P < 0.05). In the assessment of reduction loss, the percentage was 16.9% (11/65) for the plain radiographs and 7.7% (5/65) for the 3-D CT scans (P < 0.05). For the 5 patients with reduction loss, which were observed by two imaging modalities, the mean Constant-Murley score was 61.0 ± 1.6. The patients with reduction loss, observed only in plain radiographs but not CT images, had good shoulder function (Constant-Murley score: 82.7 ± 1.0). CONCLUSIONS: Our data reveal that 3-D CT images are more reliable than plain radiographs in the assessment of the prognostic factors of reduction loss of fractures of the proximal part of the humerus with treatment of locking plates; this reliable CT technique can serve as an effective guideline for the subsequent clinical management of patients.

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.

An ultrasensitive nanowire-transistor biosensor for detecting dopamine release from living PC12 cells under hypoxic stimulation.

Dopamine (DA) is an important neurotransmitter that is involved in neuronal signal transduction and several critical illnesses. However, the concentration of DA is extremely low in patients and is difficult to detect using existing electrochemical biosensors with detection limits typically around nanomolar levels (∼10(-9) M). Here, we developed a nanoelectronic device as a biosensor for ultrasensitive and selective DA detection by modifying DNA-aptamers on a multiple-parallel-connected (MPC) silicon nanowire field-effect transistor (referred to as MPC aptamer/SiNW-FET). Compared with conventional electrochemical methods, the MPC aptamer/SiNW-FET has been demonstrated to improve the limit of DA detection to <10(-11) M and to possess a detection specificity that is able to distinguish DA from other chemical analogues, such as ascorbic acid, catechol, phenethylamine, tyrosine, epinephrine, and norepinephrine. This MPC aptamer/SiNW-FET was also applied to monitor DA release under hypoxic stimulation from living PC12 cells. The real-time recording of the exocytotic DA induced by hypoxia reveals that the increase in intracellular Ca(2+) that is required to trigger DA secretion is dominated by an extracellular Ca(2+) influx, rather than the release of intracellular Ca(2+) stores.

Research status and application prospects of digital technology in orthopaedics.

In the last 10 years, basic and clinical research in orthopaedics has developed rapidly. Understanding of orthopaedic disorders involves not only routine diagnosis, but also the pursuit of highly efficient and accurate three-dimensional imaging of the intra- and extra-medullary distribution, form and structure of orthopaedic disorders, thus allowing scientific evaluation of the indications for surgery, drawing up of the best surgical plan, minimization of operative trauma and the earliest possible restoration of limb function. Meanwhile, the most important type of basic research, which was previously biomechanical research, has gradually become computational biomechanics based on in vitro cadaver experiments. This review aims to summarize the research status and application prospects of digital technology in orthopaedics, including virtual reality technology, reverse engineering and rapid prototyping techniques, computational biomechanics, computer navigation technology and management of digitization of medical records.

Three-dimensional morphological characteristics measurement of ankle joint based on computed tomography image post-processing.

BACKGROUND: As precise positioning of ankle radiography is not possible, quantitative measurement of all syndesmotic parameters on repeated ankle X-ray films may be of little value. The purpose of this study was to provide a set of scientific and objective evaluation criteria for assessing the quality of ankle fracture reduction accurately and reliably by an intelligent combining three-dimensional (3-D) computed tomography (CT) measurement model. METHODS: From June 2008 to March 2011, all the thin-slice CT images of 100 cases (50 males and 50 females) with normal ankle joint scanned by 16-slice spiral CT were collected. Two-dimensional (2-D) and 3-D images of ankle joints were generated by using multiple planar reconstruction (MPR) and surface shaded display (SSD) respectively. The relevant parameters about bone structures and their relationship were measured and analyzed based on 3-D topological narrow division technique and 3-D measurement techniques combining essential elements of point, line and surface. RESULTS: In this study, the mean distance from lateral malleolus tip to talocrural articular surface, the tip of medial malleolus anterior colliculus to talocrural articular surface and lateral malleolus tip to the tip of medial malleolus anterior colliculus were (22.83 ± 1.12) mm, (12.84 ± 1.09) mm, and (61.18 ± 2.03) mm respectively in male group, and (20.16 ± 1.00) mm, (10.30 ± 1.05) mm and (53.00 ± 1.40) mm respectively in female group. The above three parameters were correlated with gender, height and weight (P < 0.05). However, the mean perpendicular distance from lateral malleolus tip to the plane through the tip of medial malleolus anterior colliculus, the talocrural angle, later clear space, medial clear space, and the superior clear space were (9.93 ± 0.29) mm, (10.01 ± 0.38)°, (1.94 ± 0.16) mm, (2.78 ± 0.19) mm, and (3.14 ± 0.15) mm respectively in 100 cases, were not significance correlated with gender, height and weight (P > 0.05). CONCLUSIONS: This study could provide a certain amount of relevant data for the standard of injured ankle anatomical reduction and the second surgery planning after malunion. The methods of measurement are reliable, reproducible, and easy to apply in practice.

[Study of the morphology of heel spur and clinical significance: base on three-dimensional computed tomography].

OBJECTIVES: To evaluate the characteristic morphology of heel spur, and to investigate the relationship of heel spur and plantar heel pain. METHODS: From June 2005 to April 2009, 210 cases (254 feet) with heel spur (according to Denis Pain Scale) were divided into cases group 1 (P2, n = 46), 2 (P3, n = 44), 3 (P4, n = 42), 4 (P5, n = 36) and controls group (P1, n = 42). Three-dimensional reconstruction of heel spur was performed in all groups using volume rendering based on multi-slice CT data by Super Image orthopedics edition 1.0. The characteristic morphology of heel spur was observed and the data were measured and analyzed, involving the width of basilar part, the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur. RESULTS: Parts of cases groups displayed coarse arcuate edge and undersurface with one or more little heel spurs adhere to heel spur, of which the numbers were greater than controls group, especially in cases group 4. No significant difference of the width of basilar part of heel spur was found among 5 groups (F = 2.32, P > 0.05). However, obvious difference was found in the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur (F = 8.23, 6.82, 5.87, P < 0.05). Compared with the controls group, the angle between heel spur and planta pedis of cases groups had higher degrees, but the difference of the other data presented irregular. CONCLUSIONS: The characteristic morphology of heel spur varies in patients associated with plantar heel pain. No correlation is found between the severity and the morphological data, including the width of basilar part, the length, the angle between heel spur and planta pedis, and the angle between the longitudinal axis of calcaneus and heel spur.

[Effects of primary tumor excision on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice].

OBJECTIVE: To investigate the effects of primary tumor excision on osteosarcoma angiogenesis and pulmonary metastasis, and explore its possible mechanism and clinical significance. METHODS: The tumor-bearing nude mice were constructed by injection of human osteosarcoma cell suspension, and divided into primary tumor resection, amputation and normal groups. The level of VEGF and endostatin was examined by ELISA assay. The hemoglobin content in Matrigel pellets was measured with HiCN method. Pulmonary metastasis was detected with dilated-squash technique and immunohistochemical staining. RESULTS: The serum VEGF and endostatin level was significantly decreased in the primary tumor excision group compared with that in the normal and control groups after operation, but endostatin decreased more prominently [VEGF: (71.43 +/- 9.15) pg/ml vs. (115.81 +/- 4.38) pg/ml, (111.68 +/- 12.26) pg/ml, P < 0.01; ES: (40.77 +/- 5.41) ng/ml vs. (123.18 +/- 5.94) ng/ml, (128.06 +/- 4.52) ng/ml, P < 0.01]. The HB contents in Matrigel pellets increased in the primary tumor excision group compared with that in normal and control groups [(36.55 +/- 2.35) g/L vs. (16.84 +/- 1.15) g/L, (16.29 +/- 1.10) g/L, P < 0.01]. The rate of pulmonary metastasis in tumor excision group was much higher than that in the un-excised groups (80.0% vs. 40.0% and 35.0%, P < 0.05). CONCLUSION: The excision of primary tumor can promote osteosarcoma angiogenesis and pulmonary metastasis, so anti-angiogenic treatment after operation has instructive clinical significance in preventing tumor metastasis.

Assessment of subtalar joint neutral position: a cadaveric study.

BACKGROUND: Subtalar joint (STJ) neutral position is the position typically used by clinicians to obtain a cast representation of a patient's foot before fabrication of biomechanical functional orthosis. But no method for measuring STJ neutral position has been proven accurate and reproducible by different testers. This study was conducted to investigate the STJ neutral position in normal feet in cadavers. METHODS: Twelve fresh-frozen specimens of amputated lower legs were used. Pressure-sensitive films were inserted into the anterior and posterior articulation of STJ. The contact areas for various foot positions and under axial loads of 600 N were determined based on the gray level of the digitized film. The STJ neutral positions were determined as the ankle-foot position where the maximum contact area was achieved, because the neutral position of a joint was defined as the position where the concave and convex surfaces were completely congruous. RESULTS: In ankle-foot neutral position, the contact area of STJ was (2.79 +/- 0.24) cm(2). In the range of motion of adduction-abduction (ADD-ABD), the maximum contact area was (3.00 +/- 0.26) cm(2) when the foot was positioned 10 degrees of ABD (F = 221.361, P < 0.05). In the range of motion of dorsiflexion-plantarflexion (DF-PF), the maximum contact area was (3.61 +/- 0.25) cm(2) when the foot was positioned 20 degrees of DF (F = 121.067, P < 0.05). In the range of motion of inversion-eversion (INV-EV), the maximum contact area was (3.14 +/- 0.26) cm(2) when the foot was positioned 10 degrees of EV (F = 256.252, P < 0.05). CONCLUSIONS: Joints, such as STJ, therefore, are not necessarily in neutral position when the ankle-foot is placed in the traditional concept of neutral position. The results demonstrate that the most approximate STJ neutral position was in the foot position of 10 degrees of abduction, 20 degrees of dorsiflexion and 10 degrees of eversion.

Cerebral ischemia and Alzheimer's disease: the expression of amyloid-beta and apolipoprotein E in human hippocampus.

Growing evidence suggests a synergistic and perhaps etiological relationship between vascular disease and Alzheimer's disease (AD), which is characterized by the progressive accumulation of amyloid-beta peptide (Abeta). Moreover, apolipoprotein E (ApoE) has also been shown to be associated with AD and cerebral ischemia. It seems that cerebral ischemia may play an important, both direct and indirect, role in the pathogenesis of AD. We investigated the expression and distribution of Abeta1-40, beta1-42 and ApoE in human hippocampus after cerebral ischemia in this study to determine the role of cerebral ischemia in Alzheimer's disease. Our study has demonstrated that the accumulation of both Abeta1-40 and beta1-42 were increased dramatically and consistently after cerebral ischemia. Neuronal ApoE immunoreactivity was also significantly increased in all ischemic groups compared with controls. The most likely stimulus for the increased Abeta1-40, Abeta1-42 and ApoE immunoreactivity in the CA1 and CA3 neurons is the ischemic conditions, and their upregulation, in turn, may partly explain the contribution of cerebral ischemia to the pathogenesis of AD. Therefore our observations provide a basis for establishing therapeutic strategies aimed at preventing ischemic insults and subsequent neurodegeneration in AD.

[Relationship between serum load of HBV-DNA and therapeutic effect of oxymatrine in patients with chronic hepatitis B].

OBJECTIVE: To study the relationship between serum load level of HBV-DNA and therapeutic effect of oxymatrine in patients with chronic hepatitis B. METHODS: Forty-four patients of chronic hepatitis B were divided into two groups, the treated group was treated with oxymatrine 0.4 g/d by intramuscular injection for 3 months, the control group was treated with some liver protecting agents to estimate the therapeutic effect. The serum level of HBV-DNA was determined by quantitative polymerase chain reaction (PCR) before and after treatment. RESULTS: The seroconversion rate of HBV-DNA and HBeAg in the treated group was 43.47% and 43.47% respectively, which was obviously better than those in the control group respectively (P < 0.05), the quantity of HBV-DNA decreased after treatment from 10(6.83 +/- 1.27) copy/ml to 10(3.35 +/- 3.08) copy/ml. Among them, in patient with HBeAg negative conversion, the pretreatment quantity of HBV-DNA was 10(6.30 +/- 1.42) copy/ml, while in those with no HBeAg negative conversion, it was 10(7.23 +/- 1.23) copy/ml, the difference was significant. CONCLUSION: Oxymatrine is effective in treating chronic hepatitis B. The therapeutic effect is better for patients with lower quantity of serum HBV-DNA.