HDAC3 aberration-incurred GPX4 suppression drives renal ferroptosis and AKI-CKD progression.

Acute kidney injury (AKI) progression to chronic kidney disease (CKD) represents a unique renal disease setting characterized by early renal cellular injury and regulated cell death, and later renal fibrosis, of which the critical role and nature of ferroptosis are only partially understood. Here, we report that renal tubular epithelial ferroptosis caused by HDAC3 (histone deacetylase 3) aberration and the resultant GPX4 suppression drives AKI-CKD progression. In mouse models of AKI-CKD transition induced by nephrotoxic aristolochic acid (AA) and folic acid (FA), renal tubular epithelial ferroptosis occurred early that coincided with preferential HDAC3 elevation and marked suppression of a core anti-ferroptosis enzyme GPX4 (glutathione peroxidase 4). Intriguingly, genetic Hdac3 knockout or administration of a HDAC3-selective inhibitor RGFP966 effectively mitigated the GPX4 suppression, ferroptosis and the fibrosis-associated renal functional loss. In cultured tubular epithelial cells, HDAC3 over-expression or inhibition inversely affected GPX4 abundances. Further analysis revealed that Gpx4 promoter contains a typical binding motif of transcription factor KLF5 (Kruppel-like factor 5). HDAC3 and KLF5 inducibly associated and bound to Gpx4 promoter upon AA treatment, leading to local histone hypoacetylation and GPX4 transactivation inhibition, which was blocked by RGFP966 and a KLF5 inhibitor ML264, respectively, suggesting that KLF5 co-regulated the HDAC3-incurred Gpx4 transcription inhibition. More importantly, in AKI-CKD mice receiving a GPX4 inactivator RSL3, the anti-ferroptosis and renoprotective effects of RGFP966 were largely abrogated, indicating that GPX4 is an essential downstream mediator of the HDAC3 aberration and renal ferroptosis during AKI-CKD transition. Together, our study identified a critical epigenetic pathway of ferroptosis during AKI-CKD transition and suggested that the strategies preserving GPX4 by HDAC3 inhibition are potentially effective to reduce renal ferroptosis and slow AKI-CKD progression.

Deep learning for predicting refractive error from multiple photorefraction images.

BACKGROUND: Refractive error detection is a significant factor in preventing the development of myopia. To improve the efficiency and accuracy of refractive error detection, a refractive error detection network (REDNet) is proposed that combines the advantages of a convolutional neural network (CNN) and a recurrent neural network (RNN). It not only extracts the features of each image, but also fully utilizes the sequential relationship between images. In this article, we develop a system to predict the spherical power, cylindrical power, and spherical equivalent in multiple eccentric photorefraction images. Approach First, images of the pupil area are extracted from multiple eccentric photorefraction images; then, the features of each pupil image are extracted using the REDNet convolution layers. Finally, the features are fused by the recurrent layers in REDNet to predict the spherical power, cylindrical power, and spherical equivalent. RESULTS: The results show that the mean absolute error (MAE) values of the spherical power, cylindrical power, and spherical equivalent can reach 0.1740 D (diopters), 0.0702 D, and 0.1835 D, respectively. SIGNIFICANCE: This method demonstrates a much higher accuracy than those of current state-of-the-art deep-learning methods. Moreover, it is effective and practical.

Practice and experience of regional medical center entrance linkage and closed-loop management under the wartime situation of the COVID-19 in China.

On 28 July 2021, the first indigenous case of novel coronavirus pneumonia (COVID-19) emerged in Yangzhou, marking the beginning of a public health crisis caused by the new coronavirus pneumonia. It is a significant challenge for hospitals to carry out prevention and control measures to ensure the safety of medical professionals and patients when facing the changes in an epidemic situation. Subei People's Hospital, as one of the first group of "Grade III-class A" hospitals in Jiangsu Province and the Yangzhou Regional Medical Centre, responded quickly and scientifically to prevent and control the disease. A closed-loop management system was implemented at the hospital entrance (consisting of the outpatient clinic, emergency clinic, fever clinic, and buffer ward) and an epidemic prevention and control group was established with the assistance of multiple departments. This group optimized the pre-screening and triage system, standardized the fever clinic consultation process, and improved the construction of an information-based prevention and control network so that patients were detected, diagnosed, isolated, and treated early. The emergency management capability was improved to achieve zero missed consultations of patients attending for COVID-19 and to effectively maintain medical order during this critical period. This current report systematically summarizes the operational practices and the effectiveness achieved by implementation of the entrance closed-loop management in the hospital and analyzed the key operational issues for future reference by medical institutions and management departments.

Open synovectomy treatment for intra- and extraarticular localized pigmented villonodular synovitis of the knee: a case report.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferative neoplastic process that commonly affects synovial-lined anatomic spaces. The diffuse type (DPVNS) is characterized by invasion of the entire joint synovium, while the localized type (LPVNS) is characterized by a relatively normal synovial appearance. This report describes a unique case of massive intraarticular LPVNS with an extraarticular extension through the lateral patellar retinaculum. No similar cases have been found in the literature. CASE PRESENTATION: A 58-year-old woman had a history of hyperuricemia and knee trauma and presented with unilateral knee acute swelling and pain symptoms with sudden onset. Recent expansion of the LPVNS caused the development of a tender palpable soft tissue mass in the anterolateral aspect of the knee and acute reduced mobility. Preoperative magnetic resonance imaging of the knee revealed the presence of only the soft tissue mass and mild degenerative changes. Open synovectomy was performed successfully to excise the mass. Intraoperatively, macroscopic features of the bright brown inflamed synovium suggested LPVNS, which was confirmed histopathologically. Postoperatively, the symptoms of limited mobility and pain were appreciably relieved. Recurrence was not observed during the clinical follow-up at 1, 6 or 18 months after surgery. CONCLUSIONS: Here, we report the unique case of localized pigmented villonodular synovitis of the knee in a misdiagnosed patient with intra- and extraarticular lesion, which might be attributed to the history of knee trauma and the focal defect of the lateral patellar retinaculum. Open synovectomy effectively relieved the symptoms of limited mobility and pain and no recurrence was observed prior to 18 months postoperatively. To reduce misdiagnosis, MRI examinations are recommended for all patients suspected of having PVNS, including those who have a history of hyperuricemia.

Hydrogen sulfide protects against IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis in chondrocytes and ameliorates osteoarthritis.

The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1ß-induced chondrocytes were identified. Our data revealed decreased H2 S expression in both human degenerative OA cartilage tissue and IL-1ß-induced chondrocytes. Pretreatment with the H2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1ß-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1ß-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1ß-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2 S may antagonize IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.

Honokiol protects against epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overproduction in rats post­laminectomy.

Epidural fibrosis (EF)­induced failed back surgery syndrome (FBSS) in patients post­laminectomy remains a medical challenge. Although the scarring mechanisms remain unclear, the majority of aetiological studies have reported fibroblast dysfunction. Honokiol, the major bioactive constituent of the magnolia tree, exerts a variety of pharmacological effects, including anti­proliferative and anti­fibrotic effects, on various cell types. The present study investigated whether honokiol attenuates EF progression. In vitro, it was found that honokiol inhibited excessive fibroblast proliferation induced by transforming growth factor­ß1 (TGF­ß1) and the synthesis of extracellular matrix (ECM) components, including fibronectin and type I collagen, in a dose­dependent manner. These effects were attributed to the ability of honokiol to suppress the activity of connective tissue growth factor (CTGF), which is indispensable for the progression of fibrosis. Mechanistically, honokiol attenuated the TGF­ß1­induced activation of the Smad2/3 and mitogen­activated protein kinase (MAPK) signalling pathways in fibroblasts. In vivo, honokiol reduced the proliferation of fibroblasts and the synthesis of ECM components, thus ameliorating EF in a rat model post­laminectomy. Taken together, these preclinical findings suggest that honokiol deserves further consideration as a candidate therapeutic agent for EF.

The incidence and mortality trends of bone lymphoma in the United States: An analysis of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: In recent years, studies on bone lymphoma and its histologic types have reached a mature stage. However, reports on the incidence and incidence-based mortality trends of bone lymphoma are scanty. METHODS: Patients with bone lymphoma in the U.S. were selected from Surveillance, Epidemiology, and End Results (SEER) database (1975-2016), and categorized based on age, sex, race, tumor location, SEER Historic Stage A and histologic type. Data on the incidence (1975-2016) and incidence-based mortality (1985-2016) were directly obtained from the SEER program. Annual percentage change (APC) and 95% confidence intervals (CIs) were calculated using the joinpoint regression analysis program. RESULTS: Overall, 13,058 bone lymphoma cases diagnosed in resident patients of the U.S. were included in incidence analysis between 1975 and 2016 as follows: 6080 cases in 1975-1999, 3796 cases in 2000-2009, and 3182 cases in 2010-2016. Of these cases, 6888 died of bone lymphoma between 1985 and 2016. The overall incidence rates dramatically increased from 0.89 per 100,000 person-years in 1975 to 1.36 per 100,000 person-years in 2016. Incidence trend sharply increased from 1975 to 2009, and then stabilized between 2009 and 2016. Overall incidence-based mortality trends sharply increased from 1985 to 2016 without a joinpoint. Following the demographic and tumor characteristics, the trends of incidence and incidence-based mortality exhibited similar patterns. CONCLUSION: Considering various characteristics (age, sex, race, tumor location, SEER Historic Stage A, and histologic type), we established that the incidence trend of bone lymphoma has sharply been increasing over the decades, however, in the recent years, the trend has stabilized. Besides, between 1985 and 2016, the incidence-based mortality had been sharply increasing without a turning point. These findings could give insights for clinicians to elaborately assess the epidemiology and risk factors of bone lymphoma.

The Emerging Roles of the Gaseous Signaling Molecules NO, H2S, and CO in the Regulation of Stem Cells.

Stem cell technology can be used in tissue engineering and regenerative medicine to transplant stem cells of somatic, embryonic, or induced pluripotent origin, which have tremendous potential for the treatment of currently incurable diseases. Stem cells can maintain their stemness through their self-renewal capability while promoting tissue repair and regeneration through differentiation into various target tissue cells. These two major processes of stem cell biology are precisely regulated via extracellular and intracellular signals. Gaseous signaling molecules have recently been identified to play important roles in both physiology and pathophysiology, and inhalable nitric oxide (iNO) has even been applied as a therapeutic agent. Compared with chemical formulations, these molecules have lower molecular weights and are more likely to pass through the blood-brain barrier and between cells. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), three major gaseous signaling molecules involved in biological functions, are emerging as regulators of stem cell processes such as self-renewal, differentiation, survival, anti-apoptotic effects, proliferation, and immune rejection. Although many reviews concerning the roles of gaseous signaling molecules in different diseases or systems are available, few have focused on the roles of these molecules in the regulation of stem cells. Therefore, the aim of this paper is to systematically review the current literature on the functions and mechanisms of the gaseous signaling molecules NO, H2S, and CO in different types of stem cells and to summarize the effects of these molecules on stem cell biology and in therapy.

Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition.

Intervertebral disc degeneration (IDD) is a complicated disease in patients. The pathogenesis of IDD encompasses cellular oxidative stress, mitochondrion dysfunction and apoptosis. Melatonin eliminates oxygen free radicals, regulates mitochondrial homoeostasis and function, stimulates mitophagy and protects against cellular apoptosis. Therefore, we hypothesize that melatonin has beneficial effect on IDD by mitophagy stimulation and inhibition of apoptosis. The effects of melatonin on IDD were investigated in vitro and in vivo. For the former, melatonin diminished cellular apoptosis caused by tert-butyl hydroperoxide in nucleus pulposus (NP) cells. Mitophagy, as well as its upstream regulator Parkin, was activated by melatonin in both a dose and time-dependent manner. Mitophagy inhibition by cyclosporine A (CsA) partially eliminated the protective effects of melatonin against NP cell apoptosis, suggesting that mitophagy is involved in the protective effect of melatonin on IDD. In addition, melatonin was demonstrated to preserve the extracellular matrix (ECM) content of Collagen II, Aggrecan and Sox-9, while inhibiting the expression of matrix degeneration enzymes, including MMP-13 and ADAMTS-5. In vivo, our results demonstrated that melatonin treatment ameliorated IDD in a puncture-induced rat model. To conclude, our results suggested that melatonin protected NP cells against apoptosis via mitophagy induction and ameliorated disc degeneration, providing the potential therapy for IDD.

SIRT3 Activation by Dihydromyricetin Suppresses Chondrocytes Degeneration via Maintaining Mitochondrial Homeostasis.

Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and OA, as well as the therapeutic effects of DHM on mitochondrial homeostasis in TNF-α-treated chondrocytes. The relationship between SIRT3 and OA was confirmed by detecting SIRT3 level in vitro and in vivo. Mitochondrial dysfunction was evaluated in chondrocytes with or without SIRT3 knockdown. Furthermore, the effects of DHM on mitochondrial homeostasis were performed in TNF-α-treated rat chondrocytes in vitro. In this study, our results showed that the SIRT3 level was decreased in mouse OA cartilage, corresponding to the reduced SIRT3 level in TNF-α-treated chondrocytes in vitro. SIRT3 knockdown induced mitochondrial dysfunction in chondrocytes. Moreover, our study demonstrated that DHM might activate SIRT3 to protect rat chondrocytes from TNF-α-induced degeneration and protective effects of DHM on mitochondrial homeostasis in chondrocytes attributed to enhanced SIRT3. Collectively, SIRT3 deficiency is implicated in OA development and DHM exerts anti-degeneration effect by maintaining mitochondrial homeostasis via a SIRT3-dependent manner in chondrocytes.

Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration.

It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1ß, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1ß-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1ß-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1ß stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1ß-induced NP cells.

The radiologic assessment of posterior ligamentous complex injury in patients with thoracolumbar fracture.

PURPOSES: To discuss whether radiologic parameters are closely related to posterior ligamentous complex (PLC) injury identified by magnetic resonance imaging (MRI). METHODS: One hundred and five thoracolumbar fracture (T11-L2) patients were retrospectively analyzed in the study. The patients were divided into different groups by the status of the PLC on MRI: intact, incompletely ruptured and ruptured. The radiographic parameters included the anterior edge-inferior endplate angle (AEIEA), the anterior edge displacement (AED), the Cobb angle (CA), the region angle (RA), the sagittal index (SI), local kyphosis (LK), the anterior/posterior vertebral height ratio (A/P ratio), the anterior vertebral height ratio (AVH ratio), and bony fragment in front of the fractured vertebra (BFOFV). T test, Pearson's Chi-square and multivariate logistic regression were calculated for the variables. RESULTS: Supraspinous ligament (SSL) rupture versus intact was not only associated with the occurrence of AEIEA <70°, LK >25° and BFOFV, but also with increased AED (9.89 ± 3.12 mm and 9.34 ± 3.36 mm, P = 0.034), RA (9.52 ± 3.93° versus 7.91 ± 3.99°, P = 0.042), and LK (23.98 ± 5.88° versus 15.55 ± 5.28°, P = 0.021). The indications for interspinous ligament (ISL) injury included AEIEA <75°, AEIEA <70° (P = 0.004 and P < 0.001, respectively), increased AED (P = 0.010), LK >25° (P = 0.024), AVH (P < 0.001), and BFOFV (P < 0.001). Multivariate logistic regression analysis revealed that AEIEA <70° and BFOFV were high risk factors for SSL rupture [standard partial regression coefficients (betas) were 0.439 and 0.408, P = 0.003 and 0.001, respectively] and ISL rupture (betas were 0.548 and 0.494, P = 0.028 and 0.001, respectively). Increased AED and LK >25° were also related to either ISL rupture (P = 0.035 and 0.001, respectively) or SSL rupture (P = 0.014 and 0.008, respectively). CONCLUSION: Our data may prove useful in a preliminary assessment of the PLC integrity based on plain radiographic imaging. We show that radiologic indications, such as AEIEA <70°, BFOFV, LK >25°, and increased AED, are correlated with ISL or SSL rupture, while RA, CA, SI, A/P ratio, and AVH ratio are not.

Changes in Pelvic Incidence, Pelvic Tilt, and Sacral Slope in Situations of Pelvic Rotation.

STUDY DESIGN: Digitally reconstructed radiograph-based study. OBJECTIVE: Using a computer-based method to determine what degree of pelvic rotation is acceptable for measuring the pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). The effectiveness of a geometrical formula used to calculate the angle of pelvic rotation proposed in a previous article was assessed. SUMMARY OF BACKGROUND DATA: It is unclear whether PI, PT, and SS are valid with pelvic rotation while acquiring a radiograph. MATERIALS AND METHODS: Ten 3-dimensionally reconstructed models were established with software and placed in a neutral orientation to orient all of the bones in a standing position. Next, 140 digitally reconstructed radiographs were obtained by rotating the models around the longitudinal axis of each pelvis in the software from 0 to 30 degrees at 2.5-degree intervals. PI, PT, and SS were measured. The rotation angle was considered to be acceptable when the change in the measured angle (compared with the "correct" position) was <6 degrees. The rotation angle (α) on the images was calculated by a geometrical formula. Consistency between the measured value and the set angle was assessed. RESULTS: The acceptable maximum angle of rotation for reliable measurements of PI was 17.5 degrees, and the changes in PT and SS were within an acceptable range (<6 degrees) when the pelvic rotation increased from 0 to 30 degrees. The effectiveness of the geometrical formula was shown by the consistency between the set and the calculated rotation angles of the pelvis (intraclass correlation coefficient=0.99). CONCLUSIONS: Our study provides insight into the influence of pelvic rotation on the PI, PT, and SS. PI changes with pelvic rotation. The acceptable maximum angle for reliable values of PI, PT, and SS was 17.5 degrees, and the rotation angle of the pelvis on a lateral spinopelvic radiograph can be calculated reliably.

A novel micro-CT-based method to monitor the morphology of blood vessels in the rabbit endplate.

PURPOSE: The aim of this study was to develop a novel method for observing the morphology of the blood vessels in the rabbit endplate. METHODS: Twenty 6-month-old rabbits were used in this study. The blood vessels in the L5 endplate in Group A were injected with iohexol and Group B with barium sulfate. Group C was the control group with saline. To optimize the study, Group B was divided into two subgroups: Group B-1 was injected with 100% (w/v) barium sulfate and Group B-2 with 50% (w/v). After injection, the L4-L5 vertebral body was excised and the cranial endplate of L5 was scanned using a micro-CT scanner. Models of the vertebral endplate and vessels were reconstructed using the 3D reconstruction software (Mimics 16.0) by calculating a bone threshold value, and then merged these two models to create a superimposed model. RESULTS: The 3D vessel models could not be created in Groups A and C, but they were clearly visualized in Group B. In the 3D model, the blood vessels extended from the subchondral bone to the endplate, and the density of the blood vessels in the area of the nucleus pulposus (NP) was higher than in the annulus fibrosus. CONCLUSIONS: The results of this study suggest that the blood vessels in the rabbit endplate can be clearly observed by the method described using barium sulfate [the 50% (w/v) gave better results compared with the 100% (w/v)]. The information from the 3D vessel structure could provide essential data to help us understand the nutrient pathways within the vertebral endplate.

Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo.

Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose- and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells' apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD.

Minimally invasive cortical bone trajectory screws placement via pedicle or pedicle rib unit in the lower thoracic spine: a cadaveric and radiographic study.

PURPOSE: To evaluate the feasibility of cortical bone trajectory (CBT) screws fixation via pedicle or pedicle rib unit in the cadaveric thoracic spine (T9-T12). METHODS: Computed tomography (CT) images of 100 patients are analyzed by multiplanar reconstruction. Ten cadaveric thoracic spines are used to insert 4.5 × 35.0 mm CBT screws at all levels from T9 to T12. RESULTS: Maximal screw length obtained by CT has a tendency to gradually increase from T9 (29.64 mm) to T12 (32.84 mm), and the difference reaches significant level at all levels except T9 versus T10 (P < 0.01). Maximal screw diameter increases from T9 (4.92 mm) to T12 (7.47 mm) and the difference reaches significant level among all levels (P < 0.01). Lateral angle increases from T9 (7.37°) to T12 (10.47°), and the difference reaches significant level among all levels except T11 versus T12. Cephalad angle from T9 to T12 are 19.03°, 22.10°, 25.62° and 27.50° (P < 0.01), respectively. The percentage of the inner and outer pedicle breakage are 2.5 and 22.5 %, respectively. The violation of lateral pedicle wall occurs at T9 and T10, especially for women at T9. CONCLUSIONS: Both radiographic and cadaveric studies establish the feasibility of CBT screws placement via pedicle or pedicle rib unit in the lower thoracic spine (T9-T12). Furthermore, our measurements are also useful for application of this technique.

Risk factors of kyphosis recurrence after implant removal in thoracolumbar burst fractures following posterior short-segment fixation.

PURPOSE: Our aim was to evaluate the results of short-segment pedicle instrumentation with screw insertion in the fracture level and find factors predicting kyphosis recurrence in thoracolumbar burst fractures. METHODS: We retrospectively analysed 122 patients with thoracolumbar burst fracture who were divided into two groups: kyphosis recurrence and no kyphosis recurrence. Pre-operative radiographic data comprising Cobb angle (CA), regional angle, anterior vertebra height (AVH), upper intervertebral angle, vertebral wedge angle (VWA), pre-anteroposterior A/P approach, superior endplate fracture, load-sharing classification (LSC) score and clinical data including age, visual analogue scale (VAS) score, thoracolumbar injury classification and severity score were compared between groups. T test, Pearson's chi-square and multivariate logistic regression were calculated for variables. RESULTS: CA, VWA and AVH were significantly corrected after surgery. CA changed from 23.7 to 3.0 (p <0.001), VWA from 38.7 to 9.6 (p <0.001) and AVH from 48.8 % to 91.2 % (p <0.001). These parameters were well maintained during the follow-up period with a mild, tolerant loss of correction. Neurological function and pain were significantly improved without deterioration. Age, pre-A/P and pre-AVH < 50 % influenced kyphosis recurrence (p = 0.032, 0.026, 0.011, respectively). CONCLUSIONS: Short-segment pedicle instrumentation including the fractured vertebra was effective in treating thoracolumbar burst fractures. The loss of correction at follow-up after implant removal was associated with age, A/P ratio and anterior vertebral height < 50 %.

A Method to Prevent Occipitocervical Joint Violation Using Plain Radiography During Percutaneous Anterior Transarticular Screw Fixation.

STUDY DESIGN: A prospective study of anterior transarticular screw (ATS) fixation patients. OBJECTIVE: To develop a method to determine screw tip position through plain radiography after percutaneous ATS fixation to prevent occipitocervical joint (OCJ) violation. SUMMARY OF BACKGROUND DATA: No studies using plain radiography to prevent OCJ violation during percutaneous ATS fixation have been performed. METHODS: In total, 34 subjects (with 68 screws) who had undergone percutaneous ATS fixation were enrolled. To evaluate the screw tip location in relation to the C1 lateral mass (LM), the screw tip positions were graded 1, 2, or 3 on anteroposterior (AP) radiographs, and I, II, or III on lateral radiographs. OCJ violation was analyzed by postoperative computed tomography (CT). RESULTS: Screws with tips located lower (tip I) in the LM did not result in OCJ violation. Only one tip in the tip 3 position showed OCJ perforation, and this screw was also located in tip III. Screw perforation rates of tip 1-tip II, tip 1-tip III, and tip 2-tip III were the highest (100%), followed by tip 2-tip II (10.5%) and tip3-tip III (10%). CONCLUSION: This study provides insights into OCJ violation during percutaneous ATS fixation. According to AP radiography, a percutaneous ATS with the screw tip located in the lateral part of the LM resulted in a lower rate of OCJ perforation, whereas screws located in the medial LM resulted in the highest rate of perforation. Percutaneous ATS with the screw tip located in the neutral part of the LM should ensure that the screw tip is below the upper part of the LM, preventing OCJ violation. These findings may help surgeons assess screw positioning both during and after the operation. LEVEL OF EVIDENCE: 3.

Clinicopathological significance of CD206-positive macrophages in patients with acute tubulointerstitial disease.

OBJECTIVE: To investigate the clinicopathological significance of CD206-positive macrophage expression in patients with acute tubulointerstitial disease, including acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). METHODS: Renal tissue samples from patients with ATN (n=10), AIN (n=10), and minimal change disease (MCD, as disease control, n=8) as well as tissue from normal control kidneys (negative control, n=3) were included in this study. The expression of CD206 and CD68 in renal tissues was detected by immunohistochemistry or immunofluorescence. RESULTS: CD206-positive cells accumulated in areas around damaged tubular cells and regenerating tubules. Compared with AIN patients, ATN patients had lower serum albumin, lower proteinuria, lower urinary osmolality and higher plasma hemoglobin, (P=0.002; P=0.01; P<0.001; P=0.002, respectively). CD206-positive cells could also be observed in the tubular basement membrane and tubule lumen. Some CD206-positive cells infiltrated into the tubular cells in patients with AIN. Compared to patients with ATN, patients with AIN had more CD206-positive cells (P=0.005). In the ATN patients, there were more CD206-positive cells in ischemic tissue. CD206-positive cells were negatively correlated with hemoglobin (r=-0.565, P=0.009) and positively correlated with serum albumin (r=0.496, P=0.026), urinary osmolality (r=0.567, P=0.009) and proteinuria (r=0.460, P=0.041). There was no correlation between CD206-positive cells and eGFR. CONCLUSION: CD206-positive macrophages are involved in the pathogenesis of acute tubular necrosis and acute interstitial nephritis.

[Abnormal percentage of memory B cells in tonsils and peripheral blood in clinical progression of IgA nephropathy].

OBJECTIVE: To observe an abnormal expression of humoral immune response induced by memory B cells in tonsils and peripheral blood of patients with IgA nephropathy (IgAN), the variation of memory B cells after tonsillectomy, and to discover the role of tonsillectomy in IgAN. METHODS: In the study, 28 patients were diagnosed as IgAN via renal biopsy, and 27 patients suffering from chronic tonsillitis without nephritis and 10 normal human beings were selected as controls. The expression of memory B cells in the tonsils and peripheral blood was tested by flow cytometry, and the same method was used to test the variation of the expression of memory B cells in peripheral blood of patients with IgAN after tonsillectomy. RESULTS: In this study, higher percentages of memory B cells were observed in tonsil and peripheral blood of IgAN patients, which were 5.72%±5.26%, 4.92%±5.10%. After tonsillectomy, the percentage of memory B cells was 1.10%±0.65%, lower than that before tonsillectomy (P<0.05). Meanwhile, in tonsils and peripheral blood, the percentage of memory B cells varied with the variation of the urinary findings of the IgAN patients. CONCLUSION: The percentage of memory B cell in tonsils and peripheral blood could predict disease progression of IgAN to a certain extent.