The mitotic rate as a prognostic biomarker after preoperative radiotherapy for high-grade limb/trunk soft tissue sarcoma.

PURPOSE: Currently there is no generally accepted standardized approach for the pathological evaluation of soft tissue sarcoma (STS) histology appearance after preoperative radiotherapy (PORT). This study aimed to investigate the prognostic value of pathological appearance after PORT for patients with high-grade limb/trunk STS. METHODS: A cohort of 116 patients with high-grade STS of the limb/trunk treated with PORT followed by resection were evaluated. Patient characteristics, imaging tumor morphology (size, volume), and histopathology (mitotic and necrosis rate, viable cell, hyalinization/fibrosis cytopathic effect) were reviewed and reassessed. Disease free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the hazard ratio was derived from Cox proportional hazard models. Two predictive nomograms were calculated based on significant predictors identified. RESULTS: The 5-year DFS and OS were 52.9% and 70.3%, respectively. Tumor size before (HR:1.07, 95%CI: 1.01-1.14) and after PORT (HR:1.08, 95%CI: 1.01-1.14), tumor volume (HR:1.06, 95%CI: 1.01-1.12), mitotic rate after PORT (HR: 1.06, 95%CI: 1.02-1.11), mitotic rate change after PORT (HR:1.04, 95%CI:1.00-1.09) were independent risk factors for DFS. Tumor size before (HR:1.08, 95%CI: 1.03-1.14) and after PORT (HR:1.09, 95%CI: 1.04-1.15), tumor volume (HR:1.05, 95%CI: 1.01-1.09), mitotic rate after PORT (HR: 1.09, 95%CI: 1.04-1.13), mitotic rate change after PORT (HR:1.05, 95%CI:1.01-1.09) were independent risk factors for OS. The C-index of pathologic predictive nomogram based on mitotic rate for DFS and OS were 0.67 and 0.73, respectively. The C-index of morphology-pathology predictive nomogram for OS was 0.79. CONCLUSION: Tumor size before and after PORT, tumor volume, mitotic rate after PORT, mitotic rate change after PORT were independent risk factors for DFS and OS in high-grade STS patients treated with PORT. The mitotic rate, independent of tumor morphology, showed its potential as a prognostic biomarker for pathologic evaluation in patients treated with PORT.

Endoprosthetic replacement with preservation of the epiphysis for proximal tibial reconstruction after osteosarcoma resection in children: a case report.

BACKGROUND: Limb salvage surgery is an important method for treating malignant tumors of the bone involving the adjacent parts of the major joints in children. This technique allows for preservation of limb function, especially in the lower limb. However, the reconstruction of the proximal end of the tibia after removing the tumor mass with a rational scale to preserve the total knee joint and reduce limb length discrepancy presents a challenge. CASE PRESENTATION: We present a case of osteosarcoma of the proximal tibia. After being treated with an extended tumor resection, the proximal tibia of the child was restructured using endoprosthetic replacement with epiphyseal preservation. This procedure preserves the entire articular surface and growth plate of the knee joint of the affected limb and provides a feasible alternative protocol for retaining the function and growth potential of the affected limb. The patient remained disease-free and normal limb motor function was observed during the 3.5 year follow-up since the initial surgery. CONCLUSIONS: Preservation of the epiphysis enabled our patient to perform better limb function after limb-saving surgery as a result of his undamaged knee joint and minimized limb-length discrepancy. We believe that endoprosthetic replacement with preservation of the epiphysis can provide the best strategy for reconstruction after resection of focal malignant tumors in long bones without epiphytic involvement.

Bizarre parosteal osteochondromatous proliferation in the distal ulna where the lesion is continuous with the medullary cavity: a case report.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Associations of residential greenness with bone mineral density and osteoporosis: the modifying effect of genetic susceptibility.

OBJECTIVES: To investigate the associations of residential greenness with bone mineral density and incident osteoporosis, and further evaluate the potential modifying effect of genetic susceptibility. METHODS: We used the Normalised Difference Vegetation Index (NDVI) at various buffer distances, including 300 m (NDVI300m), 500 m (NDVI500m), 1000 m (NDVI1000m) and 1500 m (NDVI1500m), to serve as indicators of greenness. We fitted linear regression, logistic regression and Cox proportional hazard models to assess the associations of residential greenness with estimated bone mineral density (eBMD), prevalent osteoporosis and incident osteoporosis, respectively. With the Polygenic Risk Score (PRS) for osteoporosis, we further assessed the joint effects of genetic risk and greenness on the risk of osteoporosis. We conducted causal mediation analyses to explore potential mediators. RESULTS: Each IQR increase in NDVI300m was associated with 0.0007 (95% CI 0.0002 to 0.0013) increase in eBMD, 6% lower risk of prevalent osteoporosis (OR 0.94; 95% CI 0.92 to 0.97) and 5% lower risk of incident osteoporosis (HR 0.95; 95% CI 0.93 to 0.98). The joint effects of greenness and PRS on the risk of osteoporosis displayed a clear dose-response pattern. Compared with individuals exposed to low NDVI levels and high genetic risk, those exposed to high NDVI levels and low genetic risk had a 56% (95% CI 51% to 61%) lower risk of osteoporosis. The primary mediators in the association between greenness and incident osteoporosis were identified as PM2.5 and NO2. CONCLUSIONS: Residential greenness was associated with higher bone mineral density and decreased risk of incident osteoporosis.

Unraveling the potential mechanisms of the anti-osteoporotic effects of the Achyranthes bidentata-Dipsacus asper herb pair: a network pharmacology and experimental study.

Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients' quality of life. The Achyranthes bidentata-Dipsacus asper (AB-DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB-DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB-DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of "OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18." Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug-compound-target-pathway-disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB-DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D-C-T-P-T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and ß-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB-DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB-DA for treating osteoporosis in clinical practice.

The incidence, risk factors and outcomes of wound complications after preoperative radiotherapy and surgery for high grade extremity soft tissue sarcomas: A 14-year retrospective study.

OBJECTIVE: The aim of this study was to analyze the wound complication (WC) rate and to determine the risk factors for WC in patients with soft tissue sarcoma treated with preoperative radiotherapy followed by surgical resection. METHODS: Using the database of Oxford University Hospital (OUH) we retrospectively studied 126 cases of soft tissue sarcomas treated with preoperative radiotherapy and surgery between 2007 and 2021. WC were defined as minor wound complication (MiWC) not requiring surgical intervention or major wound complication (MaWC) if they received a secondary surgical intervention. Univariate and multiple regression analyses were performed using frequency of WC and MaWC as a dependent variable. RESULTS: The incidence of WC and MaWC was 43.7% (55/126) and 19% (24/126). Age (OR:1.03, 95%CI: 1.00-1.06, p = 0.016), tumor size (OR:1.11, 95%CI:1.01-1.21, p = 0.027) and tumor site namely proximal lower limb vs upper limb (OR:10.87, 95%CI 1.15-103.03, p = 0.038) were risk factors on multivariate analysis. In nested case control analysis, the incidence of MaWC was 43.6% (24/55), the mean recovery time is 143 days in patients with MaWC. Smoking increases the risk for MaWC (OR:8.32, 95%CI:1.36-49.99, p = 0.022). The time interval between surgery and wound complication reduces the risk for MaWC (OR:0.91, 95%CI:0.84-0.99, p = 0.028) in multivariate analysis. CONCLUSIONS: Age, tumor site and size are risk factors for WC requiring preoperative radiotherapy. Smoking and the time interval between surgery and wound complication are risk factors for MaWC as compared with MiWC. MaWC rate (19%) are comparable to those in postoperative radiotherapy and surgery alone.

Multi Stimuli-Responsive Aggregation-Induced Emission Active Polymer Platform Based on Tetraphenylethylene-Appended Maleic Anhydride Terpolymers.

Multi stimuli-responsive aggregation-induced emission (AIE) active polymers have great application prospects in high-tech innovations. Herein, three types of tetraphenylethylene (TPE)-containing monomers were synthesized and utilized in preparing TPE-appended maleic anhydride terpolymers. After hydrolysis, the produced TPE-appended maleic acid terpolymers have identical linear charge densities but different "primary" structures, which created widely varied microenvironments around the carboxylate and TPE groups. Benefiting from the synergistic interaction of the TPE moiety and the terpolymer conformation change, the TPE-appended maleic acid terpolymers exhibited fluorescence changes in response to multi stimuli, including pH, ionic strength, Ca2+, and bovine serum albumin. On both the "signaling" and the "stimuli acceptor" sides, the multi stimuli-responsive fluorescence behavior was influenced markedly by the terpolymer primary structure. The fundamental insights gained in the present work are important for developing an efficient and versatile stimuli-responsive AIE-active polymer platform for chemo-sensing, bioimaging, and so on.

The Role of a Multidisciplinary Team in the Diagnosis and Treatment of Bone and Soft Tissue Sarcomas: A Single-Center Experience.

Bone and soft tissue sarcomas with complex and varied clinical, imaging, and pathological characteristics cannot be diagnosed and treated by a single discipline, as each discipline has some limitations. This study aimed to explore the role of a multidisciplinary team (MDT) in the diagnosis and treatment of bone and soft tissue sarcomas over the past four consecutive years. The subjects were 269 patients discussed during MDT meetings at a Bone and Soft Tissue Sarcomas Center in South China. The diagnosis, relapse diagnosis, unplanned resection, management of pulmonary nodules, and treatment of refractory and advanced tumors were compared to similar data provided in the literature to (i) determine whether the MDT significantly affected the diagnosis and treatment of bone and soft tissue sarcomas, and (ii) explore trends in the types of patients with bone and soft tissue sarcomas and treatment decision-making since the establishment of the MDT. Results revealed that the MDT significantly improved preoperative diagnostic accuracy for patients with bone and soft tissue sarcomas; the accuracy of diagnosis and relapse diagnosis by the MDT reached 95.42% and 100%, respectively. After an MDT discussion, the positive pathology rate for extended resection after unplanned resection was 81.2%. The overall accuracy of the MDT in determining the nature of pulmonary nodules was 87.1-91.9%. For patients presenting with pulmonary nodules in osteosarcoma, no statistically significant difference in survival was shown between cases discussed by the MDT and those without an MDT discussion (p = 0.5751). Collectively, the MDT can play a positive role in accurate preoperative diagnosis, relapse diagnosis, the decision to extend resection after an unplanned resection, and the diagnostic accuracy of pulmonary nodules.

Subset analysis of safety and efficacy in asian patients treated with RRx-001 across three clinical trials.

RRx-001, a CD47 antagonist via its inhibition of MYC and the γ-subtype of the peroxisome proliferator-activated receptor (PPAR) has been associated to date with minimal toxicity. The aim of this post-hoc analysis was to evaluate the toxicity and efficacy of RRx-001 in Asian patients since RRx-001, in the context of multiple Phase 3 studies, will be administered in China and Chinese territories as well as potentially throughout the rest of Asia. Patients received 4 mg of RRx-001 in three different antitumor clinical trials with chemotherapy and/or radiation and a retrospective subset efficacy and toxicity analysis was conducted for patients with Asian ancestry in comparison to patients with other ethnic backgrounds. The toxicity and efficacy data from these studies were similar between Asians and the rest of the treated patients. While the sample sizes are too small to draw definitive conclusions, at a dose of 4 mg, when RRx-001 is combined with chemotherapy, no apparent differences in terms of safety and efficacy are observed in cancer patients with Asian ancestry.

Activation Mechanism of Coal Gangue and Its Impact on the Properties of Geopolymers: A Review.

Coal gangue is one of the industrial solid wastes that may harm the human body through the ecosystem for a long time. Using coal gangue in geopolymer preparation can effectively reduce cement output and meet the sustainability requirements. In this paper, the physical and chemical characteristics, including the heavy metal content, of coal gangue from different producing areas are described. Then, the mechanism of physical activation (mechanical and thermal activation), chemical activation, and compound activation of coal gangue are illustrated. The machinability, as well as the mechanical, microscopic, and toxicity consolidation properties of geopolymers prepared from coal gangue, are summarized and analyzed. The results indicate that the coal gangue geopolymers can have higher mobility and mechanical strength than cement-based composites by adjusting high calcium element material, alkali activator content, Na2SiO3 modulus, and curing condition. After physical activation, coal gangue is used in geopolymer preparation with a chemical activator (alkali excitation agent), which effectively forms a three-dimensional silicon aluminate polymer network. The pore structure is dense, the physical fixation and chemical bonding are strengthened, and the solidification and adsorption of heavy metal ions are improved. Further, it can also be applied to solidifying radioactive waste, which is following the future development direction.

Transition-Metal-Free, Site-Selective C-F Arylation of Polyfluoroarenes via Electrophotocatalysis.

Direct CAr-F arylation is effective and sustainable for synthesis of polyfluorobiaryls with different degrees of fluorination, which are important motifs in medical and material chemistry. However, with no aid of transition metals, the engagement of CAr-F bond activation has proved difficult. Herein, an unprecedented transition-metal-free strategy is reported for site-selective CAr-F arylation of polyfluoroarenes with simple (het)arenes. By merging N,N-bis(2,6-diisopropylphenyl)perylene-3,4,9,10-bis(dicarboximide)-catalyzed electrophotocatalytic reduction and anodic nitroxyl radical oxidation in an electrophotocatalytic cell, various polyfluoroaromatics (2F-6F and 8F), especially inactive partially fluorinated aromatics, undergo sacrificial-reagents-free C-F bond arylation with high regioselectivity, and the yields are comparable to those for reported transition-metal catalysis. This atom- and step-economic protocol features a paired electrocatalysis with organic mediators in both cathodic and anodic processes. The broad substrate scope and good functional-group compatibility highlight the merits of this operationally simple strategy. Moreover, the easy gram-scale synthesis and late-stage functionalization collectively advocate for the practical value, which would promote the vigorous development of fluorine chemistry.

A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC).

For close to 40 years small-cell lung cancer (SCLC) was adrift, as listless, and as idle as a painted ship on a painted ocean, with nary a breeze to blow in the direction of clinical progress or change. The preferred decades-old first line regimen was etoposide-platinum, to which ≥50% of patients respond, followed by decades-old, tired topotecan in second line for platinum sensitive patients, full stop, because there were no approved therapeutic options (nor generally any compelling experimental ones) in third line or beyond. In 2012 SCLC was designated by the U.S. Congress as a "recalcitrant" tumor type and for good reason: because most patients relapse, after the generally favorable response in first line, respond poorly, if at all to subsequent therapies, and rarely survive beyond 1 year. A significant sea change occurred in 2018 with the approval of nivolumab followed by pembrolizumab and atezolizumab in 2019, durvalumab in 2020, accelerated approval for lurbinectedin in 2020 and trilaciclib in 2021 for myelosuppression. In 2021, the US indications for nivolumab and pembrolizumab were withdrawn. Suddenly, a tumor type, whose name was virtually synonymous with stalled progress and movement, and which was much less well studied and funded than its more prevalent cousin, non-small cell lung cancer (NSCLC), finds itself in the eye of the storm, that is, at the epicenter of an intense flurry and ferment of activity, not all of it positive. This review surveys approved drugs and select up-and-coming ones in development for extensive stage SCLC.

Using Chinese Coal Gangue as an Ecological Aggregate and Its Modification: A Review.

Coal gangue is a kind of industrial solid waste with serious ecological and environmental implications. Producing concrete with coal gangue aggregate is one of the green sustainable development requirements. This paper reviews the properties and preparation methods of Chinese gangue aggregate, studies the influence of gangue aggregate on concrete properties and the prediction model of gangue concrete, and summarizes the influence of modified materials on gangue concrete. The studies analyzed in this review show that different treatments influence the performance of coal gangue aggregate concrete. With the increase in the replacement ratio of coal gangue aggregate in concrete, the concrete workability and mechanical performance are reduced. Furthermore, the pore structure changes lead to decreased porosity, greatly affecting the durability. Coal gangue is not recommended for producing high-grade concretes. Nevertheless, pore structure can be improved by adding mineral admixtures, fibers, and admixtures to the coal gangue concrete. Hence, the working properties, mechanical properties, and durability of the concrete can be improved effectively, ensuring that coal gangue concrete meets engineering design requirements. Adding modified materials to coal gangue concrete is a viable future development direction.

Ancient Mitogenomes Reveal the Origins and Genetic Structure of the Neolithic Shimao Population in Northern China.

Shimao City is considered an important political and religious center during the Late Neolithic Longshan period of the Middle Yellow River basin. The genetic history and population dynamics among the Shimao and other ancient populations, especially the Taosi-related populations, remain unknown. Here, we sequenced 172 complete mitochondrial genomes, ranging from the Yangshao to Longshan period, from individuals related to the Shimao culture in northern Shaanxi Province and Taosi culture in southern Shanxi Province, Middle Yellow River basin. Our results show that the populations inhabiting Shimao City had close genetic connections with an earlier population in the Middle Neolithic Yangshao period of northern Shaanxi Province, revealing a mostly local origin for the Shimao Society. In addition, among the populations in other regions of the Yellow River basin, the Shimao-related populations had the closest maternal affinity with the contemporaneous Taosi populations from the Longshan period. The Shimao-related populations also shared more affinity with present-day northern Han populations than with the minorities and southern Han in China. Our study provides a new perspective on the genetic origins and structure of the Shimao people and the population dynamics in the Middle Yellow River basin during the Neolithic period.

Case Report: Primary Intraosseous Poorly Differentiated Synovial Sarcoma of the Femur.

Primary intraosseous poorly differentiated synovial sarcoma is exceedingly rare. Here, we present a case of primary intraosseous poorly differentiated synovial sarcoma from the proximal femur in a 16-year-old girl. The case was initially misdiagnosed, but the correct diagnosis of synovial sarcoma was eventually confirmed by fluorescence in situ hybridization and next-generation sequencing. We review the literature pertaining to synovial sarcoma and show that this case is the second molecularly proven intraosseous poorly differentiated synovial sarcoma in the literature. Recognition of intraosseous synovial sarcoma composed of small round cells is imperative in order to avoid misdiagnosis of the tumor as Ewing sarcoma and other small round-cell tumors, all of which have markedly different clinical management.

Efficacy and safety of SGLT2 inhibitors in patients with heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) prognosis without therapy is poor, however introduction of a range of drugs has improved it. We aimed to perform a protocol for systematic review and meta-analysis on the effects and safety of Sodium-Glucose Transporter 2 inhibitors in HF patients. METHODS: This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. This study will use the PubMed, Cochrane Library, Embase, Web of Science, and Medline databases. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. The risk of bias of included studies is estimated by taking into consideration the characteristics including random sequence generation, allocation concealment, blinding of patients, blinding of outcome assessment, completeness of outcome data, selective reporting and other bias by Cochrane Collaboration's tool. All analyses were performed with Review Manager (RevMan) software, version 5.3 (Update Software Ltd, Oxford, Oxon, UK). RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: Sodium-glucose transporter 2 inhibitors may improve critical outcomes in HF patients, and it is apparently safe. OPEN SCIENCE FRAMEWORK REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/ZKE3Y 10.17605/OSF.IO/MP5SD.