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Background Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model, which can provide a reference for clinicians, and patients to reduce the occurrence of periprosthetic infection (2) explore the risk factors for deep infection of megaprosthesis. Hypothesis A prediction model can be established and has favorable predictive accuracy. Patients and Methods One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model. Results Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy. Discussion This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients. Level of evidence IV, retrospective, cohort study.

Bone metastasis is a common complication of cancer, and bone is the third most common metastatic site following the lung and liver. Among the various bones, spine is the most common site of metastatic tumors. The treatment goals of patients with spinal metastases are mostly palliative, with the aim of reducing pain and improving quality of life. The treatment of spinal metastases has made significant progress over the past few decades. Each new technology has tried to solve the shortcomings of its predecessors. Currently, there are no mature algorithms or specific techniques that have proven to be the best for spinal metastases, and the treatment method often relies on operator and institutional preferences or biases in some cases. Percutaneous vertebral augmentation has unique value in the management of spinal metastases, understanding its indications, surgical techniques, uses, advantages and complications is critical to providing optimal patient care. We believe that the application of percutaneous vertebral augmentation alone or combined with other techniques can achieve optimal pain relief and functional improvement in the patients with spinal metastases.

Objectives To describe the epidemiological characteristics of patients with spinal metastases between 2007 and 2019. Methods Patients with spinal metastases were identified from several clinical centers in China between January 2007 and July 2019. Demographics, primary tumor types, spinal involvement, and Clinical indicators of each patient were reviewed. Results A total of 1196 patients were included in this study, 717 males (59.95%) and 479 females (40.05%), with a male to female ratio of 1.50:1. Most patients (63.71%) were in the ages range of 50 to 69 years. The mean age was 58.6 ± 11.6 (range 13–89) years and the median age was 59.0 years. The average age of females was younger than that of males, and the difference was statistically significant. The proportion of male patients over 60 years old was higher than that of females, and the difference was statistically significant. The most common primary tumor was lung cancer (n = 437, 36.54%), followed by unknown origin (n = 194, 16.22%), kidney cancer (n = 78, 6.52%), breast cancer (n = 76, 6.35%), and liver/biliary cancer (n = 75, 6.27%). The most common primary tumor was lung cancer in both males and females, followed by unknown origin in males and breast cancer in females. There were 730 patients (61.04%) in the subgroup of the number

OBJECTIVE To clarify the morphological, biochemical, and biomechanical effects of peracetic acid-ethanol sterilization processing to human hamstring tendon allografts for different time periods. METHODS Thirty-two fresh-frozen human hamstring tendon allografts obtained from an allograft supplier were prepared and incubated in peracetic acid-ethanol solution (PES) containing 1% v/v peracetic acid and 24% v/v ethanol. Specimens were randomly classified into four groups according to the PES processing time (untreated as the control group, 30 min as the PES30 group, 120 min as the PES120 group, and 240 min as the PES240group). Light microscopy with hematoxylin-eosin and toluidine blue were performed, along with transmission electron microscopy (TEM) to measure the collagen fibril diameters and their distributions, from which the collagen fibril index (CFI) and mass average diameter (MAD) were calculated. The thermal stability and collagen denaturation were analyzed by differential scanning calorimetry (DSC) and collagen denaturation test by α-chymotrypsin. Cyclic loading and failure testing were applied on five tendons from each group, from which the cyclic creep strain, elastic modulus, maximum stress, maximum strain, and strain energy density were calculated. RESULTS Tendons in the control, PES30, PES120 groups showed similar regularly aligned collagen fibers in light microscopy images, while the images from the PES240 group revealed relatively disordered and heterogeneous collagen bundles with larger interfiber spaces. TEM analysis showed that the mean diameter (F = 3.09, P = 0.04) was lower in the PES120 group (87.15 ± 4.76 nm) than it was in the control group (99.39 ± 9.19 nm) but not statistically (P = 0.05). Moreover, the CFI value in the PES30 group (65.37 ± 4.14%) was the lowest among groups (all P ≤ 0.01), while no variance existed in density and MAD among groups (F = 2.09, P = 0.13, and F = 0.27, P = 0.85, respectively). The onset temperature (H = 8.74, P = 0.03) and peak temperature (H = 9.97, P = 0.02) were decreased in the PES30 group compared to the control group (P = 0.02 and P = 0.01, respectively), but there were no differences in enthalpy of denaturation among groups (F = 2.20, P = 0.17). The collagen denaturation test revealed lower hydroxyproline concentrations in PES-treated specimens with no statistical differences among groups (H = 8.86, P = 0.07). The maximum stress showed variance (F = 10.52, P

Aseptic loosening is a common prosthetic failure mode. The purpose of this study was to identify dose-response relationship between length of femoral stem and aseptic loosening. We collected data of patients who underwent distal femoral prosthetic replacements at our institution from 2001 to 2017. Cox regression and two-piecewise regression model were used to analyze the associations between stem length and aseptic loosening. Significant association of length of femoral stem with aseptic loosening was observed in multivariate model and a non-linear relationship could be found from the smoothed curve. In two-piecewise model, an inflection point was calculated to be 143 mm. On the left of the inflection point, every 1 mm increase in the length of stem indicated that the risk of aseptic loosening could be reduced by 6%. There was a significant non-linear relationship between the length of femoral stem and aseptic loosening, and the inflection point was 143 mm.

Background Megaprosthetic replacement is one of the main methods for reconstructing mega bone defects after tumor resection. However, the incidences of complication associated with tumor prostheses were 5-10 times higher than that of conventional total knee arthroplasty. The objective of this study is to establish and validate a nomogram model which can assist doctors and patients in predicting the prosthetic survival rates. Methods Data on cancer patients treated with tumor prosthesis replacements at our institution from November 2001 to November 2017 were collected. The potential risk factors which were well-studied and shown to be associated with megaprosthetic failure were analyzed. A nomogram model was established using independent risk factors screened out by multivariate regression analysis. The concordance index and calibration curve were selected for internal validation of the predictive accuracy of nomogram. Results The 3-, 5-, 10-, and 15-year prosthetic survival rates were 92.8%, 88.6%, 74.1%, and 48.3%, respectively. The prosthetic motion mode, body mass index, type of reconstruction, type of prosthesis, and length of bone resection were independent risk factors for tumor prosthetic failure. A nomogram model was established using these significant predictors, with a concordance index of 0.77 and a favorable consistency between predicted and actual prosthetic failure rate according to the internal validation, indicating that the nomogram model had acceptable predictive accuracy. Conclusion The prediction model identifies high-risk patients for whom attached preventive measures are required. Future studies regarding reduction in incidence of prosthetic failure should attach importance to these high-risk patients.

Objectives To summarize the epidemiological characteristics of patients following surgery for spinal metastases retrospectively and make a univariate analysis to identify independent variables that could affect the operation decision making. Methods This was a multicenter retrospective review of patients with spinal metastasis who were treated with surgery from 1 January 2007 to 31 July 2019. Basic clinical data were analyzed retrospectively by univariate analysis to identify independent variables that could affect the decision of operation modalities, including gender, age, spinal metastatic site, Frankel score, Karnofsky performance score (KPS), spinal instability neoplastic score (SINS), visual analogue scale (VAS), Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, primary tumor, extraspinal metastasis, visceral metastasis, and bone lesion (osteolytic, osteoblastic or mixed). Results A total of 580 patients including 332 males and 248 females were enrolled in the study with an average age of 58.26 years old (range, 13-86 years old). The most common spinal metastatic level was the thoracic vertebra (190 [32.76%]), followed by the lumbar vertebra (146 [25.17%]), cervical vertebra (47 [8.10%]), and sacral vertebra (35 [6.03%]). Metastases involving more than two sites of the cervical, thoracic, lumbar, and sacral vertebrae arose in 162 (27.93%) patients. For primary tumor, there were 198 (34.14%) cases of lung cancer, 41 (7.07%) cases of kidney cancer, 39 (6.72%) cases of breast cancer, 38 (6.55%) cases of gastrointestinal cancer, 35 (6.03%) cases of lymphoma and myeloma, 25 (4.31%) cases of prostate cancer, 24 (4.14%) cases of liver cancer, 23 (3.97%) cases of mesenchymal tissue sarcoma, 20 (3.45%) cases of thyroid cancer, and 84 (14.48%) cases were tumor with unknown origin. Sixty-three (10.86%) patients received minimally invasive surgery, 460 (79.31%) patients received palliative surgery, and the remaining 57 (9.83%) received tumor resection. According to the univariate analysis, the KPS score, SINS score, VAS score, Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, and bone lesion (osteolytic, osteoblastic or mixed) were independent and favorable factors affecting the surgery modalities. Conclusions Surgical treatment for spinal metastases was mainly to relieve pain, rebuild spinal stability, improve nerve function, control local tumors, and improve the quality of life of patients. For middle-aged and elderly patients with good general conditions, severe pain, spinal pathological fracture, spine instability and without urinary and fecal incontinence, early surgical treatment should be actively carried out.

Background Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model which can provide a reference for clinicians and patients to reduce the occurrence of periprosthetic infection; (2) explore the risk factors for deep infection of megaprosthesis. Hypothesis A prediction model can be established and has favorable predictive accuracy. Patients and methods One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model. Results Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy. Discussion This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients. Level of evidence IV, retrospective, cohort study.

We determined the possible associated determinants and analyzed whether gp96-associated antigenic peptides can be found in renal cell carcinoma (RCC). The gp96-peptide complexes were chromatographically purified from resected tumor tissue of RCC patients. SDS-PAGE and Western blot analysis confirmed gp96 using the gp96 monoclonal antibody, and its concentration was measured using BCA. Approximately 20 to 50 μg gp96-peptide complexes was obtained from 1 g RCC tissue. The mass spectrometry (MS) analysis of the eluted peptides included the initial profiling using matrix-assisted laser desorption/ionization time-of-flight MS. Quadrupole time-of-flight MS combined with the Mascot search engine was used to identify the peptides and find proteins from primary sequence databases. MS analysis results demonstrated that the mass range of peptide associated with gp96 was from 1046.48 to 3501.56 Da. Further research confirmed the sequences of two gp96-associated peptides, namely, LVPLEGWGGNVM and PPVYYVPYVVL. However, the original protein of the two peptides could not be found. The results demonstrated that the gp96-associated peptides are small molecular peptides, and the two peptides are deduced to be RCC-associated peptides. The identified peptides were confirmed to be associated with gp96 using the protocols described above. However, the specificity and relevance of the association to the immunogenicity of gp96 remains to be examined. Further analysis must be accomplished before the findings can be applied in peptide vaccine.

Sedoheptulose-1,7-bisphosphatase (SBPase) is a Calvin cycle enzyme and functions in photosynthetic carbon fixation. We found that SBPase was rapidly carbonylated in response to methyl viologen (MV) treatments in detached leaves of Arabidopsis plants. In vitro activity analysis of the purified recombinant SBPase showed that SBPase was carbonylated by hydroxyl radicals, which led to enzyme inactivation in an H 2 O 2 dose-dependent manner. To determine the conformity with carbonylation-caused loss in enzymatic activity in response to stresses, we isolated a loss-of-function mutant sbp , which is deficient in SBPase-dependent carbon assimilation and starch biosynthesis. sbp mutant exhibited a severe growth retardation phenotype, especially for the developmental defects in leaves and flowers where SBPASE is highly expressed. The mutation of SBPASE caused growth retardation mainly through inhibition of cell division and expansion, which can be partially rescued by exogenous application of sucrose. Our findings demonstrate that ROS-induced oxidative damage to SBPase affects growth, development, and chloroplast biogenesis in Arabidopsis through inhibiting carbon assimilation efficiency. The data presented here provide a case study that such inactivation of SBPase caused by carbonyl modification may be a kind of adaptation for plants to restrict the operation of the reductive pentose phosphate pathway under stress conditions.

The biogenesis of photosystem I (PSI), cytochrome b6f (Cytb6f) and NADH dehydrogenase (NDH) complexes relies on the spatially and temporally coordinated expression and translation of both nuclear and chloroplast genes. Here we report the identification of photosystem biogenesis regulator 1 (PBR1), a nuclear-encoded chloroplast RNA-binding protein that regulates the concerted biogenesis of NDH, PSI and Cytb6f complexes. We identified Ycf1, one of the two largest chloroplast genome-encoded open reading frames as the direct downstream target protein of PBR1. Biochemical and molecular analyses reveal that PBR1 regulates Ycf1 translation by directly binding to its mRNA. Surprisingly, we further demonstrate that relocation of the chloroplast gene Ycf1 fused with a plastid-transit sequence to the nucleus bypasses the requirement of PBR1 for Ycf1 translation, which sufficiently complements the defects in biogenesis of NDH, PSI and Cytb6f complexes in PBR1-deficient plants. Remarkably, the nuclear-encoded PBR1 tightly controls the expression of the chloroplast gene Ycf1 at the translational level, which is sufficient to sustain the coordinated biogenesis of NDH, PSI and Cytb6f complexes as a whole. Our findings provide deep insights into better understanding of how a predominant nuclear-encoded factor can act as a migratory mediator and undergoes selective translational regulation of the target plastid gene in controlling biogenesis of photosynthetic complexes.

Heat stress commonly leads to inhibition of photosynthesis in higher plants. The transcriptional induction of heat stress-responsive genes represents the first line of inducible defense against imbalances in cellular homeostasis. Although heat stress transcription factor HsfA2 and its downstream target genes are well studied, the regulatory mechanisms by which HsfA2 is activated in response to heat stress remain elusive. Here, we show that chloroplast ribosomal protein S1 (RPS1) is a heat-responsive protein and functions in protein biosynthesis in chloroplast. Knockdown of RPS1 expression in the rps1 mutant nearly eliminates the heat stress-activated expression of HsfA2 and its target genes, leading to a considerable loss of heat tolerance. We further confirm the relationship existed between the downregulation of RPS1 expression and the loss of heat tolerance by generating RNA interference-transgenic lines of RPS1. Consistent with the notion that the inhibited activation of HsfA2 in response to heat stress in the rps1 mutant causes heat-susceptibility, we further demonstrate that overexpression of HsfA2 with a viral promoter leads to constitutive expressions of its target genes in the rps1 mutant, which is sufficient to reestablish lost heat tolerance and recovers heat-susceptible thylakoid stability to wild-type levels. Our findings reveal a heat-responsive retrograde pathway in which chloroplast translation capacity is a critical factor in heat-responsive activation of HsfA2 and its target genes required for cellular homeostasis under heat stress. Thus, RPS1 is an essential yet previously unknown determinant involved in retrograde activation of heat stress responses in higher plants., Author Summary As a consequence of global warming, increasing temperature is a serious threat to crop production worldwide and may influence the objectives of breeding programs. As a universal cellular response to a shift up in temperature, the heat stress response represents the first line of inducible defense against imbalances in cellular homeostasis in the prokaryotic and eukaryotic kingdoms. Given that components of the photosynthetic apparatus housed in the chloroplast are the primary susceptible targets of thermal damage in plants, the chloroplasts were proposed as sensors to a shift up in temperature. However, the mechanism by which chloroplasts regulate the expression of nuclear heat stress–responsive gene expression according to the functional state of chloroplasts under heat stress remains unknown. In this study, we have identified chloroplast ribosomal protein S1 (RPS1) as a heat-responsive protein through proteomic screening of heat-responsive proteins. We have established a previously unrecognized molecular connection between the downregulation of RPS1 expression in chloroplast and the activation of HsfA2-dependent heat-responsive genes in nucleus, which is required for heat tolerance in higher plants. Our data provide new insights into the mechanisms whereby plant cells modulate nuclear gene expression to keep accordance with the current status of chloroplasts in response to heat stress.