The association between renal pelvis urine density and the risk of severe infectious complications in patient with symptom-free hydronephrosis after shock wave lithotripsy: a multi-center prospective study.

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Primary breast diffuse large B-cell lymphoma in the rituximab era: A retrospective study of the Chinese Southwest Oncology Group.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. METHODS: A total of 5089 newly diagnosed DLBCL patients treated with rituximab-containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group-affiliated institutes were identified, of whom 135 diagnosed with PB-DLBCL were eligible for this analysis. RESULTS: PB-DLBCL accounted for 2.7% of all DLBCLs. With a median follow-up of 4.2 years, the 5-year overall survival and progression-free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5-year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high-dose methotrexate (HD-MTX) than for patients who did not (5-year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB-DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD-MTX did not experience CNS relapse. CONCLUSION: Collectively, our results indicate combined modality therapy including rituximab-containing immunochemotherapy and consolidative breast RT is a promising approach for PB-DLBCL, while HD-MTX is useful for preventing CNS relapse.

The clinical and genomic distinctions of Class1/2/3 BRAF-mutant colorectal cancer and differential prognoses.

BRAF mutations are the oncogenic drivers in colorectal cancer and V600 mutations (Class1), which lead to RAS-independent active monomers, are the most common mutation types. BRAF non-V600 mutants can be further classified as RAS-independent active dimers (Class2) and RAS-dependent impaired kinase (Class3). We retrospectively reviewed the mutational profiles of 328 treatment-naïve colorectal tumors with BRAF mutations detected using capture-based hybrid next-generation sequencing targeting 400 + cancer-related genes. The clinical and genetic distinctions of patients harboring Class1/2/3 BRAF mutations were investigated, which revealed that tumors with Class1 BRAF mutations showed more unique genomic profiles than those with Class2/3 mutations. Also, by using an external dataset from cBioPortal, we demonstrated that patients with Class3 BRAF mutations had the best survival outcomes compared to the other two subgroups. These findings promoted the development of anti-BRAF strategies by distinguishing BRAF mutant subgroups.

Clinical features and treatment outcome of lymphoepithelioma-like carcinoma from multiple primary sites: a population-based, multicentre, real-world study.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear. MATERIALS AND METHODS: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis. RESULTS: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001). CONCLUSION: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).

A novel prognostic nomogram for patients with extragastric mucosa-associated lymphoid tissue lymphoma: A multicenter study.

BACKGROUND: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression-free survival (PFS)-related nomogram. We also performed external validation of the nomogram in an independent cohort. RESULTS: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C-index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5-year PFS was 98.9% for the low-risk group and 69.3% for the high-risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low-risk group and 94.6% for the high-risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5-year PFS rates were 94.8% and 66.7% for the low-risk and high-risk groups, respectively (p < 0.001). The 5-year OS rates were 97.9% and 88.4%, respectively (p = 0.016). CONCLUSION: The nomogram could well distinguish the prognosis of low- and high-risk patients with extragastric MALT lymphoma and is thus recommended for clinical use.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Long non-coding RNA small nucleolar RNA host gene 7 facilitates the proliferation, migration, and invasion of esophageal cancer cells by regulating microRNA-625.

BACKGROUND: Esophageal cancer (EC) is a highly aggressive malignant tumor, of which esophageal squamous cell carcinoma (ESCC) constitutes the main subtype. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been extensively studied in many tumors and has been confirmed to be an oncogene; however, it has yet to be investigated in an ESCC study. Therefore, this study intended to uncover the role of SNHG7 in ESCC. METHODS: Quantitative real-time polymerase chain reaction was applied to measure the expression levels of SNHG7 and miR-625 in ESCC tumor tissues and cell lines. Cell Counting Kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay, scratch assay, and Transwell assay were conducted to assess the proliferation, migration, and invasion ESCC cell. We verified the interaction between SNHG7 and miR-625 by performing the dual luciferase reporter gene experiment. RESULTS: Compared to that in adjacent normal tissues and HET1A cell lines, the expression level of SNHG7 in ESCC tumor tissues and ESCC cell lines was up-regulated, while the expression level of miR-625 was down-regulated. ESCC cell proliferation, migration, and invasion were significantly promoted by SNHG7 overexpression but inhibited by silencing of SNHG7. Further, luciferase reporter gene experiments confirmed that SNHG7 interacted with miR-625, and rescue experiments showed that SNHG7 promoted the malignant phenotype by inhibiting miR-625. CONCLUSIONS: SNHG7 is up-regulated in ESCC tumor tissues and cell lines, while miR-625 is expressed at a low level. SNHG7 is able to facilitate the proliferation, migration, and invasion of ESCC cells by targeting miR-625.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Effect of interface mechanical discontinuities on scaffold-cartilage integration.

A consistent lack of lateral integration between scaffolds and adjacent articular cartilage has been exhibited in vitro and in vivo. Given the mismatch in mechanical properties between scaffolds and articular cartilage, the mechanical discontinuity that occurs at the interface has been implicated as a key factor, but remains inadequately studied. Our objective was to investigate how the mechanical environment within a mechanically loaded scaffold-cartilage construct might affect integration. We hypothesized that the magnitude of the mechanical discontinuity at the scaffold-cartilage interface would be related to decreased integration. To test this hypothesis, chondrocyte seeded scaffolds were embedded into cartilage explants, pre-cultured for 14 days, and then mechanically loaded for 28 days at either 1N or 6N of applied load. Constructs were kept either peripherally confined or unconfined throughout the duration of the experiment. Stress, strain, fluid flow, and relative displacements at the cartilage-scaffold interface and within the scaffold were quantified using biphasic, inhomogeneous finite element models (bFEMs). The bFEMs indicated compressive and shear stress discontinuities occurred at the scaffold-cartilage interface for the confined and unconfined groups. The mechanical strength of the scaffold-cartilage interface and scaffold GAG content were higher in the radially confined 1N loaded groups. Multivariate regression analyses identified the strength of the interface prior to the commencement of loading and fluid flow within the scaffold as the main factors associated with scaffold-cartilage integration. Our study suggests a minimum level of scaffold-cartilage integration is needed prior to the commencement of loading, although the exact threshold has yet to be identified. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Receding horizon control strategy for an electric vehicle with dual-motor coupling system in consideration of stochastic vehicle mass.

Additional degrees of freedom existed in dual-motor coupling system bring considerable challenge to the optimal control of electric vehicles. Moreover, the stochastic characteristic of vehicle mass can further increase this challenge. A receding horizon control (RHC) strategy in consideration of stochastic vehicle mass is proposed in this study to respond to this challenge. Aiming at an electric vehicle with dual-motor coupling, a Markov chain is firstly deployed to predict future driving conditions by a formulated state transition probability matrix, based on historical driving cycles in real-world. Then, future required power is predicted by the predicted driving conditions, stochastic vehicle mass and road gradient, where the stochastic vehicle mass is formulated as stochastic variables in different bus stops. Finally, dynamic programming is employed to calculate the optimal vector of the vehicle within the defined prediction horizon, and only the first control values extracted from the optimal control vector are used to execute real-time power distribution control. The simulation results show that the proposed strategy is reasonable and can at least reduce electric consumption by 4.64%, compared with rule-based strategy.

The Scaffold-Articular Cartilage Interface: A Combined In Vitro and In Silico Analysis Under Controlled Loading Conditions.

The optimal method to integrate scaffolds with articular cartilage has not yet been identified, in part because of our lack of understanding about the mechanobiological conditions at the interface. Our objective was to quantify the effect of mechanical loading on integration between a scaffold and articular cartilage. We hypothesized that increased number of loading cycles would have a detrimental effect on interface integrity. The following models were developed: (i) an in vitro scaffold-cartilage explant system in which compressive sinusoidal loading cycles were applied for 14 days at 1 Hz, 5 days per week, for either 900, 1800, 3600, or 7200 cycles per day and (ii) an in silico inhomogeneous, biphasic finite element model (bFEM) of the scaffold-cartilage construct that was used to characterize interface micromotion, stress, and fluid flow under the prescribed loading conditions. In accordance with our hypothesis, mechanical loading significantly decreased scaffold-cartilage interface strength compared to unloaded controls regardless of the number of loading cycles. The decrease in interfacial strength can be attributed to abrupt changes in vertical displacement, fluid pressure, and compressive stresses along the interface, which reach steady-state after only 150 cycles of loading. The interfacial mechanical conditions are further complicated by the mismatch between the homogeneous properties of the scaffold and the depth-dependent properties of the articular cartilage. Finally, we suggest that mechanical conditions at the interface can be more readily modulated by increasing pre-incubation time before the load is applied, as opposed to varying the number of loading cycles.

Reducing uncertainty when using knee-specific finite element models by assessing the effect of input parameters.

Little is known about knee-specific factors that influence contact mechanics. Finite Element (FE) models offer a powerful tool to study contact mechanics, but there often exists ambiguity in the exact values of the inputs (e.g., tissue properties), which can result in a range of output values. Our objective was to quantify the reduction in the range of output values (defined herein as "uncertainty") from FE models of the human knee joint when known pre-defined values are used for clinically measurable inputs. To achieve this goal, we applied a statistically augmented FE approach to three human cadaveric knees for which full geometric and kinematic data were available. Two sets of conditions were simulated: All model inputs, clinically measurable or not, were varied to represent a "normal" patient population (Condition 1); subsets of clinically measurable variable inputs were fixed at specific values (called "patient derived inputs," or PDIs) while the other variables were varied over "normal" values (Condition 2). We found that by fixing body mass index and the anterior-posterior position of the meniscal-bony insertion points, model output uncertainty was reduced by one- to three-fifths. The magnitude of uncertainty reduction was strongly influenced by the individual knee. It was observed that knees with great anterior-posterior translation during gait had greater reductions in uncertainty when PDIs were used. This study represents the first step in developing FE models of the human knee joint based on inputs that can be derived from patients in a clinical setting. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2233-2242, 2017.

Cathepsin S inhibition changes regulatory T-cell activity in regulating bladder cancer and immune cell proliferation and apoptosis.

Regulatory T cells (Tregs) are immune suppressive cells, but their roles in tumor growth have been elusive, depending on tumor type or site. Our prior study demonstrated a role of cathepsin S (CatS) in reducing Treg immunosuppressive activity. Therefore, CatS inhibition in Tregs may exacerbate tumor growth. Using mouse bladder carcinoma MB49 cell subcutaneous implant tumor model, we detected no difference in tumor growth, whether mice were given saline- or CatS inhibitor-treated Tregs. However, mice that received inhibitor-treated Tregs had fewer splenic and tumor Tregs, and lower levels of tumor and splenic cell proliferation than mice that received saline-treated Tregs. In vitro, inhibitor-treated Tregs showed lower proliferation and higher apoptosis than saline-treated Tregs when cells were exposed to MB49. In contrast, both types of Tregs showed no difference in proliferation when they were co-cultured with normal splenocytes. Inhibitor-treated Tregs had less apoptosis in splenocytes, but more apoptosis in splenocytes with MB49 conditioned media than saline-treated Tregs. In turn, we detected less proliferation and more apoptosis of MB94 cells after co-culture with inhibitor-treated Tregs, compared with saline-treated Tregs. B220+ B-cell, CD4+ T-cell, and CD8+ T-cell proliferation and apoptosis were also lower in splenocytes co-cultured with inhibitor-treated Tregs than with saline-treated Tregs. Under the same conditions, the addition of cancer cell-conditioned media greatly increased CD8+ T-cell proliferation and reduced CD8+ T-cell apoptosis. These observations suggest that CatS inhibition of Tregs may reduce overall T-cell immunity under normal conditions, but enhance CD8+ T-cell immunity in the presence of cancer cells.

Shape of chondrocytes within articular cartilage affects the solid but not the fluid microenvironment under unconfined compression.

Metabolic activity of the chondrocytes in articular cartilage is strongly related to their zone-specific shape and the composition and mechanical properties of their surrounding extracellular matrix (ECM). However the mechanisms by which cell shape influences the response of the ECM microenvironment to mechanical loading is yet to be elucidated. This relationship was studied using a biphasic multiscale finite element model of different shaped chondrocytes in the superficial and deep zones of the ECM during unconfined stress relaxation. For chondrocytes in the superficial zone, increasing the cell's initial aspect ratio (length/height) increased the deformation and solid stresses of the chondrocyte and pericellular matrix (PCM) during the loading phase; for chondrocytes in the deep zone the effect of the cell shape on the solid microenvironment was time and variable dependent. However, for superficial and deep zone chondrocytes the cell shape did not affect the fluid pressure and fluid shear stress. These results suggest that mechanotransduction of chondrocytes in articular cartilage may be regulated through the solid phase rather than the fluid phase, and that high stresses and deformations in the solid microenvironment in the superficial zone may be essential for the zone-specific biosynthetic activity of the chondrocyte. The biphasic multiscale computational analysis suggests that maintaining the cell shape is critical for regulating the microenvironment and metabolic activity of the chondrocyte in tissue engineering constructs. STATEMENT OF SIGNIFICANCE: We investigated the effect of chondrocyte shape on the cellular microenvironment using a biphasic multiscale finite element analysis. Our study showed that cell shapes affects the solid but not the fluid microenvironment of the chondrocyte, and that maintaining the cell shape is critical for regulating the microenvironment and metabolic activity of the chondrocyte in native cartilage and tissue engineering constructs. As far as we know, this is the first study on the mechanotransduction mechanisms by which cell shape influences the response of the microenvironment to mechanical loading. This study is important for understanding cell mechanobiology, not only for regulation of cell phenotype in tissue engineered constructs but, as important, for understanding changes in normal chondrocyte function after post-traumatic injury and in the initiation and progression of osteoarthritis.

Hierarchical Control Strategy for the Cooperative Braking System of Electric Vehicle.

This paper provides a hierarchical control strategy for cooperative braking system of an electric vehicle with separated driven axles. Two layers are defined: the top layer is used to optimize the braking stability based on two sliding mode control strategies, namely, the interaxle control mode and signal-axle control strategies; the interaxle control strategy generates the ideal braking force distribution in general braking condition, and the single-axle control strategy can ensure braking safety in emergency braking condition; the bottom layer is used to maximize the regenerative braking energy recovery efficiency with a reallocated braking torque strategy; the reallocated braking torque strategy can recovery braking energy as much as possible in the premise of meeting battery charging power. The simulation results show that the proposed hierarchical control strategy is reasonable and can adapt to different typical road surfaces and load cases; the vehicle braking stability and safety can be guaranteed; furthermore, the regenerative braking energy recovery efficiency can be improved.

Expression of activating transcription factor 7 is correlated with prognosis of colorectal cancer.

BACKGROUND: It is important to identify some tumor-related factors for early detection, treatment, and evaluation of prognosis in colorectal cancer (CRC). In our study, we investigated the clinical and prognostic role of activating transcription factor 7 (ATF7) in CRC. MATERIALS AND METHODS: Expression of ATF7 was detected with immunohistochemistry in 72 cases with complete follow-up data and post-operation tissue specimens. Correlation between ATF7 and other clinicopathological factors was calculated with Chi-square test and the impact of ATF7 on survival were analyzed with Log-rank test and Cox regression models. RESULTS: Among 72 cases, ATF7 expression was detected in 43 cases (59.7%) and 29 cases (40.3%) without ATF7 expression. The correlation between ATF7 expression and pathological stage was investigated (P = 0.041). The 5-year overall survival (OS) of with or without ATF7 expression was 79% versus 51% respectively (P < 0.001) and the 5-year progression free survival (PFS) was 74% versus 41% (P < 0.001). The media OS was 69 months versus 52 months (P = 0.002) and the media PFS was 65 months versus 42 months (P = 0.002). ATF7 expression and numbers of lymph nodes involvement were prognostic factors for OS according to univariated and multivariated analysis and for PFS it was ATF7 expression and lymph nodes involvement. CONCLUSION: It is negatively related between ATF7 expression and pathological stage and positive correlation with OS and PFS in CRC. ATF7 expression is a favorable factor for survival of patients with CRC.

A statistically-augmented computational platform for evaluating meniscal function.

Meniscal implants have been developed in an attempt to provide pain relief and prevent pathological degeneration of articular cartilage. However, as yet there has been no systematic and comprehensive analysis of the effects of the meniscal design variables on meniscal function across a wide patient population, and there are no clear design criteria to ensure the functional performance of candidate meniscal implants. Our aim was to develop a statistically-augmented, experimentally-validated, computational platform to assess the effect of meniscal properties and patient variables on knee joint contact mechanics during the activity of walking. Our analysis used Finite Element Models (FEMs) that represented the geometry, kinematics as based on simulated gait and contact mechanics of three laboratory tested human cadaveric knees. The FEMs were subsequently programmed to represent prescribed meniscal variables (circumferential and radial/axial moduli-Ecm, Erm, stiffness of the meniscal attachments-Slpma, Slamp) and patient variables (varus/valgus alignment-VVA, and articular cartilage modulus-Ec). The contact mechanics data generated from the FEM runs were used as training data to a statistical interpolator which estimated joint contact data for untested configurations of input variables. Our data suggested that while Ecm and Erm of a meniscus are critical in determining knee joint mechanics in early and late stance (peak 1 and peak 3 of the gait cycle), for some knees that have greater laxity in the mid-stance phase of gait, the stiffness of the articular cartilage, Ec, can influence force distribution across the tibial plateau. We found that the medial meniscus plays a dominant load-carrying role in the early stance phase and less so in late stance, while the lateral meniscus distributes load throughout gait. Joint contact mechanics in the medial compartment are more sensitive to Ecm than those in the lateral compartment. Finally, throughout stance, varus-valgus alignment can overwhelm these relationships while the stiffness of meniscal attachments in the range studied have minimal effects on the knee joint mechanics. In summary, our statistically-augmented, computational platform allowed us to study how meniscal implant design variables (which can be controlled at the time of manufacture or implantation) interact with patient variables (which can be set in FEMs but cannot be controlled in patient studies) to affect joint contact mechanics during the activity of simulated walking.