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Objective Multitargeted tyrosine kinase inhibitors (TKIs) have been approved as second‐line therapy in refractory sarcoma, prolonging progression‐free survival (PFS) but with short‐lived duration of disease control. Fruquintinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐1,2,3 with no metabolism by liver enzymes. In this retrospective study, we assessed the efficacy and safety of fruquintinib‐based treatment in patients with refractory sarcoma after developing several lines of TKI resistance. Methods We retrospectively analyzed the clinical data of patients with refractory sarcoma after they had developed several lines of resistance to TKIs and who received fruquintinib‐based treatment from November 2021 to August 2023. The primary endpoint was the progression‐free survival rate at 4 months (4m‐PFSR). Secondary endpoints were the median PFS, overall survival (OS), objective response rate, disease control rate, and adverse effects (AEs). PFS and OS were estimated using the Kaplan–Meier method. A log‐rank test was used to compare survival curves between different clinical and pathological factors. Cox proportional hazards analysis was performed to identify PFS‐related prognostic factors. Results We included 124 patients: 56 (45.2%) with osteosarcoma, 28 (22.6%) with Ewing sarcoma, seven (5.6%) with chondrosarcoma, and 33 (26.6%) with soft tissue sarcomas (STS). Only 18 (14.5%) patients received monotherapy with fruquintinib. With a median follow‐up time of 6.8 (interquartile range [IQR], 4.6–9.4) months, 22 (17.7%) patients had partial response and 78 (62.9%) had stable disease. The 4m‐PFSR was 58.4% (95% confidence interval [CI], 49.6%–67.1%). The median PFS and OS were 4.4 (95% CI, 3.9–5.0) months and 11.4 (95% CI, 10.3–12.5) months. In multivariate analysis, a high hazard ratio for progression was associated with target lesions located outside the lung and bone with 1.79 (95% CI, 1.10–2.93; p = 0.020). Eighty‐eight AEs were recorded in 47 (37.9%) patients; the most common were pneumothorax (18/124, 14.5%), diarrhea (8/124, 6.5%), oral mucositis (7/124, 5.6%), and thrombocytopenia (7/124, 5.6%). Conclusions Fruquintinib may be a potential option for patients with refractory sarcoma after developing several lines of TKI resistance, with a satisfactory efficacy and safety profile in combination therapy. However, the degree of contribution of fruquintinib to results is unclear when combined with other effective substances. Additional prospective trials of fruquintinib should be conducted, especially involving different pathological types and combination regimens.

Objective It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. Methods We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. Results All six patients were followed up for 24 to 46 months (mean follow‐up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection‐related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. Conclusion Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long‐term disease‐free survival with acceptable complications and satisfying neurological function.

Abstract Antimicrobial resistance (AMR) remains an urgent and formidable challenge to global public health. Developing new medicines or alternative therapies to address AMR is imperative. Herein, we rationally designed and synthesized a series of Au(I)‐based aggregation‐induced emission luminogens (AIEgens) to combat drug‐resistant bacterial infections. Through systematic screening, we identified an optimal AIEgen, called complex 5, which can rapidly discriminate between gram‐positive (G+) and gram‐negative bacteria (G−) bacteria, and exert robust and broad‐spectrum antimicrobial potency against diverse drug‐resistant bacterial strains, including those intractable to treat in clinic. Furthermore, extensive testing against a variety of clinical drug‐resistant isolates, coupled with the successful treatment of methicillin‐resistant Staphylococcus aureus‐infected skin wounds unequivocally validates the high efficiency and broad‐spectrum activity of complex 5. Therefore, complex 5 emerges as a promising candidate for combating drug‐resistant bacterial infections in clinic, and this work provides inspiration for developing new solutions to address the escalating global challenge of AMR.

Abstract Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen‐section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3‐IRDye800CW is synthesized by conjugating anti‐B7H3 antibody and IRDye800CW. B7H3‐IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (

Abstract Background REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. Methods A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. Results Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). Conclusion This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. Level of evidence Therapeutic study, Level III.

Abstract Background Inadequate surface matching, variation in the guide design, and soft tissue on the skeletal surface may make it difficult to accurately place the 3D-printed patient-specific instrument (PSI) exactly to the designated site, leading to decreased accuracy, or even errors. Consequently, we developed a novel 3D-printed PSI with fluoroscopy-guided positioning markers to enhance the accuracy of osteotomies in joint-preserving surgery. The current study was to compare whether the fluoroscopically calibrated PSI (FCPSI) can achieve better accuracy compared with freehand resection and conventional PSI (CPSI) resection. Methods Simulated joint-preserving surgery was conducted using nine synthetic left knee bone models. Osteotomies adjacent to the knee joint were designed to evaluate the accuracy at the epiphysis side. The experiment was divided into three groups: free-hand, conventional PSI (CPSI), and fluoroscopically Calibrated PSI (FCPSI). Post-resection CT scans were quantitatively analyzed. Analysis of variance (ANOVA) was used. Result FCPSI improved the resection accuracy significantly. The mean location accuracy is 2.66 mm for FCPSI compared to 6.36 mm (P

Abstract Background Clinical scenarios frequently present challenges when patients exhibit asymmetrical mandibular atrophy. The dilemma arises: should we adhere to the conventional All-on-4 technique, or should we contemplate placing vertically oriented implants on the side with sufficient bone mass? This study aims to employ three-dimensional finite element analysis to simulate and explore the biomechanical advantages of each approach. Methods A finite element model, derived from computed tomography (CT) data, was utilized to simulate the nonhomogeneous features of the mandible. Three configurations—All-on-4, All-on-5-v and All-on-5-o were studied. Vertical and oblique forces of 200 N were applied unilaterally, and vertical force of 100 N was applied anteriorly to simulate different masticatory mechanisms. The maximum von Mises stresses on the implant and framework were recorded, as well as the maximum equivalent strain in the peri-implant bone. Results The maximum stress values for all designs were located at the neck of the distal implant, and the maximum strains in the bone tissue were located around the distal implant. The All-on-5-o and All-on-5-v models exhibited reduced stresses and strains compared to All-on-4, highlighting the potential benefits of the additional implant. There were no considerable differences in stresses and strains between the All-on-5-o and All-on-5-v groups. Conclusions With the presence of adequate bone volume on one side and severe atrophy of the contralateral bone, while the “All-on-4 concept” is a viable approach, vertical implant placement optimizes the transfer of forces between components and tissues.

Extracellular vesicles (EVs) have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins (RNPs), owing to their ability to minimize off-target effects and immune responses. However, enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within EVs. In response, we employed the Fc/Spa interaction system, in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV membrane. Simultaneously, the B domain of the Spa protein was fused to the C domain of cargos such as Cre or spCas9. Due to the robust interaction between Fc and Spa, this method enriched nearly twice the amount of cargo within the EVs. EVs loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in vivo. Moreover, following neuron-targeting peptide RVG modification, the in vivo dosage in neural tissues substantially increased, contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target efficiency. These findings establish a robust platform for efficient EV-based SpCas9 delivery, offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

IntroductionLimited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma.MethodsA total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations.ResultsThe prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p

BackgroundThe percutaneous screw reconstruction technique, known as the “Tripod Technique,” has demonstrated favorable clinical outcomes in the management of metastatic periacetabular lesions, as evidenced by our prior investigations and corroborated by independent studies. Nevertheless, there is a steep learning curve in handling this technique, with possible complications such as intraarticular screw placement.MethodsPreoperative pelvic CT scans were acquired before surgery and utilized for the guiding frame design. A convolutional neural network model was trained with annotated data to identify the starting point and trajectory of each potential screw. A model boundary intersection detection technology was used to determine the optimal diameter and length of each screw. A non-rigid registration technology was matched with a prefabricated model of the body surface to design personalized anchoring skin pads. Finally, a polylactic acid-based guiding frame for intraoperative was custom-made with a 3D printer.Results12 patients underwent a guiding frame-assisted Tripod procedure for treatment of periacetabular metastatic lesions. An intraoperative CT scan was performed in all cases to confirm screw trajectories. Among 36 screws that were implanted, 26 screws were implanted as designed. The remaining ten screws drifted, but all remained within the intra-osseous conduit without any complications. The mean surgical time was 1.22 h with the guiding frame compared with 2.3 h without the guiding frame. Following the surgical procedure, a noteworthy enhancement in pain management, as evidenced by a reduction in scores on the visual analog scale (p < 0.01), and an improvement in functional status, as assessed through the Eastern Cooperative Oncology Group score (p < 0.01), were observed when compared to the patient’s pre-operative condition.ConclusionThis proof-of-concept investigation demonstrates that the amalgamation of AI-assisted surgical planning and additive manufacturing can improve surgical accuracy and shorten surgical duration. While access to this technology is currently constrained during its early stages of development, it is anticipated that these limitations will diminish as the potential of AI and additive manufacturing in facilitating complex orthopedic procedures becomes more evident, leading to a surge in interest and adoption of this approach.

Introduction: Femur and tibia are the most commonly affected sites for primary malignant bone tumors in children. The wide resection of the tumor frequently requires the physis to be resected. The normal growth of the unaffected limb will result in a significant limb length discrepancy at skeletal maturity. To compensate for this resulting LLD, different generations of extendible endoprostheses have been developed. Non-invasive extendable prostheses eliminate the need for surgical procedures and general anesthesia, enabling gradual and painless lengthening. Currently available non-invasive extendable prostheses focus on joint reconstruction, and no case series analysis of intercalary non-invasive extendable prosthesis has been reported. Therefore, we have designed a novel non-invasive electromagnetic extendable intercalary endoprosthesis.Methods:In vitro mechanical experiments and in vivo animal experiments were conducted.Results:In vitro experiments have confirmed that the prosthetics can extend at a constant rate, increasing by 4.4 mm every 10 min. The average maximum extension force during prosthetic elongation can reach 1306N. In animal in vivo experiments, the extension process is smooth and non-invasive, and the sheep is in a comfortable state.Discussion: The in vitro and in vivo animal studies provide evidence to support the extension reliability, laying the foundation for future large-scale validation experiments.

Abstract Aims We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. Patients and Methods A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. Results The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone‐derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p

Abstract Mix‐dimensional heterojunctions (MDHJs) photodetectors (PDs) built from bulk and 2D materials are the research focus to develop hetero‐integrated and multifunctional optoelectronic sensor systems. However, it is still an open issue for achieving multiple effects synergistic characteristics to boost sensitivity and enrich the prospect in artificial bionic systems. Herein, electrically tunable Te/WSe2 MDHJs phototransistors are constructed, and an ultralow dark current below 0.1 pA and a large on/off rectification ratio of 106 is achieved. Photoconductive, photovoltaic, and photo‐thermoelectric conversions are simultaneously demonstrated by tuning the gate and bias. By these synergistic effects, responsivity and detectivity respectively reach 13.9 A W−1 and 1.37 × 1012 Jones with 400 times increment. The Te/WSe2 MDHJs PDs can function as artificial bionic visual systems due to the comparable response time to those of the human visual system and the presence of transient positive and negative response signals. This work offers an available strategy for intelligent optoelectronic devices with hetero‐integration and multifunctions.

Abstract Background Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. Methods We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People’s Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. Results A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. Conclusions The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. Trial registration This study was approved in the Medical Ethics Committee of Peking University People’s Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Abstract Among today’s nonvolatile memories, ferroelectric-based capacitors, tunnel junctions and field-effect transistors (FET) are already industrially integrated and/or intensively investigated to improve their performances. Concurrently, because of the tremendous development of artificial intelligence and big-data issues, there is an urgent need to realize high-density crossbar arrays, a prerequisite for the future of memories and emerging computing algorithms. Here, a two-terminal ferroelectric fin diode (FFD) in which a ferroelectric capacitor and a fin-like semiconductor channel are combined to share both top and bottom electrodes is designed. Such a device not only shows both digital and analog memory functionalities but is also robust and universal as it works using two very different ferroelectric materials. When compared to all current nonvolatile memories, it cumulatively demonstrates an endurance up to 1010 cycles, an ON/OFF ratio of ~102, a feature size of 30 nm, an operating energy of ~20 fJ and an operation speed of 100 ns. Beyond these superior performances, the simple two-terminal structure and their self-rectifying ratio of ~ 104 permit to consider them as new electronic building blocks for designing passive crossbar arrays which are crucial for the future in-memory computing.

Background:After femoral oncological knee arthroplasty, some patients suffer from rotating axis fracture, which significantly impacts the life span of the rotating hinge knee (RHK) prosthesis. This research aimed to analyze the biomechanical response of anatomical gastrocnemius reconstruction and assess whether it could reduce the risk of rotating axis breakage by finite element (FE) analysis.Methods:A femur-prosthesis-tibia FE model was established using the data from CT scans. The mechanical properties of the RHK implant were quantitatively compared before and after gastrocnemius reconstruction at 6 angles: 10°, 20°, 30°, 40°, 50°, and 60°.Results:Our results showed that gastrocnemius reconstruction effectively altered the stress distribution around the rotating axis, considerably relieving the stress in the fracture-prone region. In addition, the peak stress in the rotating axis, bending axis, prosthesis stem, and femoral condyles decreased variably.Conclusion:In distal femoral resection knee arthroplasty, the rebuilding of gastrocnemius substantially improved the stress distribution within the prosthesis, thereby having the potential to reduce the risk of prosthetic fracture and prolong the overall durability of the prosthesis.

BackgroundSurgical treatment of musculoskeletal tumors in the periacetabular region present extremely difficult due to the complex anatomy and need for reconstruction. Orthopedic surgeons face more difficulties in patients with neurological conditions, which can cause increased muscle tone, an elevated risk of fractures, and compromised bone quality. There is limited evidence regarding endoprosthetic reconstruction for periacetabular tumors in individuals with neurological disorders.MethodsWe conducted a single-center retrospective study to examine the outcomes of patients with preexisting neurological conditions who underwent surgery to remove periacetabular tumors and who underwent endoprosthesis reconstruction. Clinical presentation, detailed neurological conditions, complications, and functional outcomes were studied.ResultsSixteen out of the 838 patients were identified (1.91%), with a mean follow-up time of 33 months. The primary neurological conditions encompassed Parkinson's disease, Alzheimer's disease, dementia, and cerebral ischemic stroke. Every patient was diagnosed with periacetabular lesions that were either primary or oligometastatic. They underwent tumor resection and subsequently received endoprosthetic reconstruction of the hemipelvis. Three patients developed metastasis lesions later, and two patients experienced tumor recurrence. Five cases experienced hip dislocation—one with periprosthetic fracture and one with surgical site infection. The position of the prosthetic rotating center was not correlated with dislocation. The reoperation rate was 31.25%. The cohort of patients all presented with more extended hospital stays and rehabilitation. In 3 patients, the general functional score was good, while in 6 patients, it was fair; in 7 patients, it was regarded as poor. The average MSTS93 score was 49.71%.ConclusionEndoprosthetic reconstruction after periacetabular tumor resection is an effective way to eliminate tumors and salvage limbs. However, this group of patients has an increased likelihood of secondary surgery, complications, extended hospital stay, and no significant improvement in functional outcomes. Despite the diverse nature of the cohort, it is recommended to consider enhanced soft tissue reconstruction, supervised functional recovery and rehabilitation training.

Abstract Background Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-β antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS). Methods This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-β) were performed on pre-treatment tumor samples. Results Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-β pathway or PD-L1 was not associated with treatment outcomes. Conclusions The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes. Trial registration Prospectively registered in the Ethical Review Committee of Peking University People’s Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022. ClinicalTrials.gov Identifier CTR20213001 and CTR20220390

Abstract The Multi-purpose Time Projection Chamber (TPC) for nuclear AsTrophysical and Exotic beam experiments (MATE) is being upgraded for the decay and active target experiments at the Heavy Ion Research Facility in Lanzhou (HIRFL). We have developed a gating grid driver to control the transitions between the closed and open states of the gating grid of the MATE-TPC to detect interesting rare decay events from a large amount of implanted ions. The gating grid driver is mainly composed of a digital control unit and a high-voltage switch unit. The digital control unit responds to the external trigger and generates control signals for the operation of the high-voltage control part based on the presetting instruction. The high-voltage switch unit is connected to two negative high voltages with different values and changes the voltages of neighboring wires of the gating grid based on the request for closing or opening the gate. A 500 ns switching time of the gating grid driver has been achieved from the closed to open state. The duration of the open state can be adjusted from 1 µs to 99 ms based on the experimental requirements. This gating grid driver can be used in a particle detector with a high voltage bias of up to ± 3000 V.

Extended reality (XR) technology refers to any situation where real-world objects are enhanced with computer technology, including virtual reality, augmented reality, and mixed reality. Augmented reality and mixed reality technologies have been widely applied in orthopedic clinical practice, including in teaching, preoperative planning, intraoperative navigation, and surgical outcome evaluation. The primary goal of this narrative review is to summarize the effectiveness and superiority of XR-technology-assisted intraoperative navigation in the fields of trauma, joint, spine, and bone tumor surgery, as well as to discuss the current shortcomings in intraoperative navigation applications. We reviewed titles of more than 200 studies obtained from PubMed with the following search terms: extended reality, mixed reality, augmented reality, virtual reality, intraoperative navigation, and orthopedic surgery; of those 200 studies, 69 related papers were selected for abstract review. Finally, the full text of 55 studies was analyzed and reviewed. They were classified into four groups—trauma, joint, spine, and bone tumor surgery—according to their content. Most of studies that we reviewed showed that XR-technology-assisted intraoperative navigation can effectively improve the accuracy of implant placement, such as that of screws and prostheses, reduce postoperative complications caused by inaccurate implantation, facilitate the achievement of tumor-free surgical margins, shorten the surgical duration, reduce radiation exposure for patients and surgeons, minimize further damage caused by the need for visual exposure during surgery, and provide richer and more efficient intraoperative communication, thereby facilitating academic exchange, medical assistance, and the implementation of remote healthcare.

Abstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

Abstract Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-β signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma.

Objectives The fact that studies on anti‐programmed cell death 1 (PD‐1) or its relevant ligand 1 (PD‐L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. Methods This study was a retrospective non‐intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7‐H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD‐L1 (programmed cell death ligand 1), TIM3 (mucin‐domain containing‐3), TGF‐β (TransformingGrowth Factor β), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3‐dioxygenase 1), KIRs (Killer cell Immunoglobulin‐like Receptors), and SDF‐1 (Stromal cell‐Derived Factor‐1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first‐line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ2 displayed by cross‐table, Cox proportional hazards regression model, and Kaplan–Meier plots. Results The positive rates of B7‐H3, CD47, PD‐L1, TIM3, and TGF‐β expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co‐expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. Conclusions The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily‐treated, expressed tumor immune‐associated checkpoint molecules, of which B7‐H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.

BackgroundPatients with neurological disorders often experience a high incidence of postoperative complications following proximal femur replacement (PFR) surgery. The orthopaedist faces a significant difficulty in treating Parkinson's disease (PD) because of the weakened bone condition, excessive muscle tension, and increased risk of fractures. The objective of this research is to assess the impact of PD on PFR following tumor removal.MethodsA retrospective study was conducted from 2010 to 2020, focusing on a solitary institution, analyzing 9 patients diagnosed with PD who underwent PFR with hemiarthroplasty as a result of tumor removal. The study consists of 2 men and 7 women, with an average age of 71 (SD, 12) years. We assessed the outcomes after surgery in terms of pain management, quality of life, functional ability, occurrence of complications, and survival durations.ResultsAll nine patients underwent planned surgeries. Intraoperative complications was not observed. The average length of the follow-up period was 24 (SD, 20) months, ranging from 8 to 72 months. Despite the fact that 8 patients passed away due to tumor progression, the endoprostheses were still well at that point. The preoperative VAS score of 7 (SD, 1.87) decreased to a postoperative score of 2 (SD, 1.32). The KPS was improved to73 (SD, 7) from 52 (SD, 14), postoperatively. Post-surgery, there were notable enhancements in both pain levels and the overall quality of life scores. Following the surgical procedure, individuals are able to ambulate steadily, resuming their regular daily routines. Living patients had an average MSTS score of 21 (SD, 2.5), ranging from 17 to 25. In total, there were four (44.4%) patients suffered complications after surgery, comprising of one wound dehiscence, one prosthetic fracture, one hip dislocation, and one local recurrence.ConclusionsSignificant improvements in function and pain relief can be achieved through PFR with hemiarthroplasty following tumor removal in patients with PD. The implementation of thorough preparation and carefull nursing results in reduced complications and improved outcomes in PD patients.

Chordoma is a rare malignant bone tumor with limited therapeutic options, which is resistant to conventional chemotherapy and radiotherapy, and targeted therapy is also shown with little efficacy. The long-standing delay in researching its mechanisms of occurrence and development has resulted in the dilemma of no effective treatment targets and no available drugs in clinical practice. In recent years, the role of the tumor immune microenvironment in driving tumor growth has become a hot and challenging topic in the field of cancer research. Immunotherapy has shown promising results in the treatment of various tumors. However, the study of the immune microenvironment of chordoma is still in its infancy. In this review, we aim to present a comprehensive reveal of previous exploration on the chordoma immune microenvironment and propose promising immunotherapy strategies for chordoma based on these characteristics.

Abstract CircRNAs play crucial roles in various malignancies via an increasing number of reported regulatory mechanisms, including the classic sponging mechanism between circRNAs and micro RNAs (miRNAs). We performed bioinformatic analyses and identified circTLK1 as a regulator of malignant chordoma progression. Moreover, we observed that circTLK1 showed high expression in chordoma cells and tissues, while circTLK1 interference suppressed chordoma cell proliferation and invasion. In addition, circTLK1 directly interacted with miR-16-5p, which has previously been shown to repress chordoma, and circTLK1 knockdown suppressed Smad3 expression. Chromatin immunoprecipitation sequencing further demonstrated that Smad3 acts as a positive regulator by interacting with TLK1, thereby mediating the circTLK1/miR-16-5p/Smad3 positive feedback axis. Taken together, our findings suggested that the disruption of the circTLK1/miR-16-5p/Smad3 positive feedback pathway, particularly via the Smad3 inhibitor SIS3, could be a promising therapeutic strategy.

The frequent occurrence of natural disasters caused by human activities and environmental pollution has forced people to pay attention to environmental protection. Of course, emergency rescue after natural disasters is also a great component of research. Emergency rescue often generates a large number of emergency evacuation and rescue traffic needs. In the face of scarce road resources, how to allocate limited road resources for emergency traffic needs reasonably to improve the efficiency of emergency rescue has important practical significance. This paper studies the emergency traffic distribution method and the traffic organization method of the emergency traffic network. First, on the basis of the existing traffic distribution method based on Logit model, combined with the characteristics of emergency traffic flow, an emergency multi-path traffic distributed method based on the second modified Logit model is proposed. As well as the emergency lane reversal implementation strategy is proposed according to the actual situation. Finally, an example is proposed to comprehensively verify the emergency traffic distribution method and emergency lane reversal strategy proposed in this paper. The experimental results show that the proposed method can cope with the complex scenarios of multiple emergency traffic flows and is helpful to improve the overall efficiency of emergency traffic flow.

Abstract Analog storage through synaptic weights using conductance in resistive neuromorphic systems and devices inevitably generates harmful heat dissipation. This thermal issue not only limits the energy efficiency but also hampers the very‐large‐scale and highly complicated hardware integration as in the human brain. Here we demonstrate that the synaptic weights can be simulated by reconfigurable non‐volatile capacitances of a ferroelectric‐based memcapacitor with ultralow‐power consumption. The as‐designed metal/ferroelectric/metal/insulator/semiconductor memcapacitor shows distinct 3‐bit capacitance states controlled by the ferroelectric domain dynamics. These robust memcapacitive states exhibit uniform maintenance of more than 104 s and well endurance of 109 cycles. In a wired memcapacitor crossbar network hardware, analog vector‐matrix multiplication is successfully implemented to classify 9‐pixel images by collecting the sum of displacement currents (I = C × dV/dt) in each column, which intrinsically consumes zero energy in memcapacitors themselves. Our work sheds light on an ultralow‐power neural hardware based on ferroelectric memcapacitors.

PurposeAnlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS.Materials and MethodsIn this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC.ResultsWe found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis.ConclusionTocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS.

The dielectric properties of non-stoichiometric SrMnO3 (SMO) thin films grown by molecular beam epitaxy were systematically investigated. Especially, the effects of cation stoichiometry-induced diverse types and densities of defects on the dielectric properties of SMO films were revealed. Two anomalous dielectric relaxation behaviors were observed at different temperatures in both Sr-rich and Mn-rich samples. High-temperature dielectric relaxation, resulting from a short-range Mn-related Jahn–Teller (JT) polaron hopping motion, was reinforced by an enhancement of JT polaron density in the Sr-rich film, which contained abundant SrO Ruddlesden–Popper (R-P) stacking faults. However, an excessive number of disordered Sr vacancy clusters in Mn-rich thin film suppressed the hopping path of JT polarons and enormously weakened this dielectric relaxation. Thus, The Sr-rich film demonstrated a higher dielectric constant and dielectric loss than the Mn-rich film. In addition, low-temperature dielectric relaxation may be attributed to the polarization/charge glass state.

Abstract Background The purpose of this study was to investigate the feasibility of using a three-dimensional (3D)-printed arthrodesis prosthesis for reconstruction of the proximal humeral defect after tumor resection. Methods A novel proximal humeral prosthesis was designed to restore bone continuity and shoulder arthrodesis and was fabricated via 3D printing technology. Ten patients with primary malignancies in the proximal humerus underwent intra-articular resection and replacement with this prosthesis from 2017 to 2019. Baseline and operative data, oncological and prosthetic survival, and functional status were summarized. Results This cohort consisted of 9 males and 1 female with a mean age of 32.1 ± 16.1 years. Diagnoses included 5 cases of osteosarcoma, 3 cases of chondrosarcoma and 1 each case of undifferentiated pleomorphic sarcoma and malignant myoepithelioma. The mean operative duration, intraoperative hemorrhage and postoperative length of hospitalization were 151.5 ± 61.0 min, 410.0 ± 353.4 ml and 5.3 ± 1.9 d, respectively. The mean follow-up duration was 29.3 ± 6.4 months, with a minimum of 24 months for the surviving patients. Two patients experienced local recurrence, and four patients developed distant metastases. Detachment of the taper occurred in two patients. One was managed conservatively, and the other received amputation due to concurrent tumor recurrence. The mean MSTS-93 and ASES scores and ranges of forwards flexion and abduction were 24.9 ± 3.1, 79.4 ± 8.3, 71.3 ± 19.4°, and 61.3 ± 16.4°, respectively. The functional outcomes were independent of the preservation of the axillary nerve. Histological study of the glenoid component showed evidence of bone ingrowth at the bone-prosthesis porous interface. Conclusion Application of the 3D-printed arthrodesis prosthesis might be a safe and efficacious method for functional reconstruction in patients who underwent resection of the proximal humerus, especially for those without preservation of the axillary nerve.

Abstract Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a key procedure in sacral and pelvic tumor resection that provides hemorrhage control. However, few studies have been performed to capture the effects of REBOA in a nonshock condition and provide a detailed description of the changes occurring with prolonged occlusion time. This study aimed to examine the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections following different periods of REBOA. Methods In total, 121 patients who underwent surgical tumor resections of the pelvis and/or the sacrum with the use of aortic balloon occlusion were prospectively enrolled from October 2020 to December 2021. All cases were divided into Group A (occlusion time ≤ 60 min, n = 57) and Group B (occlusion time ≥ 90 min, n = 64). Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Results Balloon inflation resulted in a significant increase in SBP from 106 to 120 mmHg and decreased to 96 mmHg immediately following balloon deflation. With the application of REBOA, the median blood loss was only 1200 ml (range, 400–7900). When deflating the REBOA, the arterial pH was lower than baseline (7.36 vs. 7.41, p

Abstract Background Gut microbiota plays an important role in the development of atopic dermatitis (AD). We aimed to elucidate research trends in gut microbiota and AD in children, to provide evidence and insights to the clinical prevention and treatment of AD in children. Methods A scoping literature review on the studies of gut microbiota and AD were conducted. Two authors independently searched Pubmed et al. databases for studies focused on gut microbiota and AD in children up to January 15, 2022. The literatures were screened and analyzed by two reviewers. Results A total of 44 reports were finally included and analyzed. Current researches have indicated that abnormal human microecology is closely associated with AD, and the disturbance of intestinal microbiota plays an important role in the occurrence and development of AD. Probiotics can correct the microbiota disorder, have the functions of regulating immunity, antioxidant, and help to restore the microecological homeostasis. However, there is still a lack of high-quality research reports on the efficacy and safety of probiotics in the prevention and treatment of AD in children. Conclusions The changes of gut microbiota are essential to the development of AD in children, which may be an effective target for the prevention and treatment of AD. Future studies with larger sample size and rigorous design are needed to elucidate the effects and safety of probiotics in AD.

Background: Osteosarcoma initially metastasing to bone only shows distinct biological features compared to osteosarcoma that firstly metastasizes to the lung, which suggests us underlying different genomic pathogenetic mechanism. Methods: We analyzed whole-exome sequencing (WES) data for 38 osteosarcoma with paired samples in different relapse patterns. We also sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms. Results: We investigated WES of 12/38 patients with high-grade osteosarcoma (31.6%) with initial bone metastasis (group A) and 26/38 (68.4%) with initial pulmonary metastasis (group B), of whom 15/38 (39.5%) had paired samples of primary lesions and metastatic lesions. We found that osteosarcoma in group A mainly carries single-nucleotide variations displaying higher tumor mutation burden and neoantigen load and more tertiary lymphoid structures, while those in group B mainly exhibits structural variants. High conservation of reported genetic sequencing over time in their evolving cladograms. Conclusions: Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases as well as better immunogenicity in tumor microenvironment.

Background Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets.Methods Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC).Results The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo.Conclusions Our study implicates that the CCL5–CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5–CCR5 axis is a potential therapeutic target in chordoma.

Despite recent developments worldwide in the therapeutic care of osteosarcoma (OS), the ongoing challenges in overcoming limitations and side effects of chemotherapy drugs warrant new strategies to improve overall patient survival. Spurred by rapid progress in biomedicine, nanobiotechnology, and materials chemistry, chemotherapeutic drug delivery in treatment of OS has become possible in recent years. Here, we review recent advances in the design of drug delivery system, especially for chemotherapeutic drugs in OS, and discuss the relative merits in trials along with future therapeutic options. These advances may pave the way for novel therapies requisite for patients with OS.

Abstract Background Perioperative neurocognitive disorders (PNDs) are common complications observed among surgical patients. Accumulating evidence suggests that neuroinflammation is one of the major contributors to the development of PNDs, but the underlying mechanisms remain unclear. Methods qPCR and ELISA analysis were used for detecting LCN2 and cytokine levels. cx3cr1 CreER/−:: R26 iDTR/− crossed mouse line was used for microglia depletion; intracranial injection of recombinant LCN2 (rLCN2) and adeno-associated viruses (AAV)-mediated shRNA silencing approaches were used for gain and loss of function, respectively. Combing with in vitro microglia cell culture, we have studied the role of LCN2 in surgery-induced cognitive decline in mice. Results We revealed that Lcn2 mRNA and protein levels were greatly increased in mouse hippocampal neurons after surgery. This surgery-induced elevation of LCN2 was independent of the presence of microglia. Gain of function by intracranial injection of rLCN2 protein into hippocampus disrupted fear memory in naive mice without surgery. Conversely, silencing LCN2 in hippocampus by AAV-shRNA protected mice from surgery-induced microglia morphological changes, neuroinflammation and cognitive decline. In vitro, application of rLCN2 protein induced the expression of several pro-inflammatory cytokines in both BV-2 and primary microglia culture. Conclusions These data suggest LCN2 acts as a signal from neuron to induce proinflammatory microglia, which contributes to surgery-induced neuroinflammation and cognitive decline in mice.

Abstract Background No available meta-analysis has been published that systematically assessed spinal fixation mechanical failure after tumor resection based on largely pooled data. This systematic review and meta-analysis aimed to investigate the spinal fixation failure rate and potential risk factors for hardware failure. Methods Electronic articles published between January 1, 1979, and January 30, 2021, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the spinal fixation failure rate and potential risk factors. Results Thirty-eight studies were finally included in the meta-analysis. The pooled spinal fixation mechanical failure rate was 10%. The significant risk factors for hardware failure included tumor level and cage subsidence. Radiotherapy was a potential risk factor. Conclusion The spinal fixation mechanical failure rate was 10%. Spinal fixation failure is mainly associated with tumor level, cage subsidence and radiotherapy. Durable reconstruction is needed for patients with these risk factors.

Ischemic stroke is a major cause of death and disability around the world. However, ischemic stroke treatment is currently limited, with a narrow therapeutic window and unsatisfactory post-treatment outcomes. Therefore, it is critical to investigate the pathophysiological mechanisms following ischemic stroke brain injury. Changes in the immunometabolism and endocrine system after ischemic stroke are important in understanding the pathophysiological mechanisms of cerebral ischemic injury. Hormones are biologically active substances produced by endocrine glands or endocrine cells that play an important role in the organism’s growth, development, metabolism, reproduction, and aging. Hormone research in ischemic stroke has made very promising progress. Hormone levels fluctuate during an ischemic stroke. Hormones regulate neuronal plasticity, promote neurotrophic factor formation, reduce cell death, apoptosis, inflammation, excitotoxicity, oxidative and nitrative stress, and brain edema in ischemic stroke. In recent years, many studies have been done on the role of thyroid hormone, growth hormone, testosterone, prolactin, oxytocin, glucocorticoid, parathyroid hormone, and dopamine in ischemic stroke, but comprehensive reviews are scarce. This review focuses on the role of hormones in the pathophysiology of ischemic stroke and discusses the mechanisms involved, intending to provide a reference value for ischemic stroke treatment and prevention.

Background: Metaphyseal fixation for endoprosthetic reconstruction after bone tumor resection is difficult due to the short residual bone length and reverse funnel shape of the metaphysis. In the current study, 3D-printed axial compressive endoprosthesis (ACE) with a short stem and intramedullary axial compressive mechanism is proposed to improve metaphyseal fixation. The rationales of ACE are that 1) intramedullary axial compress enhances the stability of endoprosthesis and facilitates bone ingrowth at the osteotomy site; 2) 3D printed porous metallic surface at osteotomy surface and stem allows bone ingrowth to achieve osseointegration.Methods: A biomechanical study was performed to explore the initial stability using Sawbones. A diaphysis and metaphyseal segmental defect were created and four fixation structures were simulated: 1) ACE; 2) ACE + lateral plate; 3) stem prosthesis + unilateral plate; 4) stem prosthesis + bilateral plates. Bending and torsional stiffness were determined with a material testing machine. The relationship between the torque of the compression nut and the axial compression force of the bone-implant surface was measured using a round gasket load sensor.Results: ACE + lateral plate was the stiffest in the bending test (sagittal 324.3 ± 110.8 N/mm, coronal 307.7 ± 8.7 N/mm). ACE + lateral plate and stem prosthesis + bilateral plates had the highest torsional stiffness (10.9 ± 1.3 Nm/° and 10.7 ± 0.2 Nm/° respectively). The bending stiffness of ACE was equivalent to stem prosthesis + bilateral plates (sagittal 196 ± 10 N/mm vs. 200 ± 7 N/mm, coronal 197 ± 14 N/mm vs. 209 ± 3 N/mm), but the torsional stiffness of ACE was inferior to stem prosthesis + bilateral plates (6.1 ± 1.3 Nm/° vs. 10.7 ± 0.2 Nm/°). Stem prosthesis + unilateral plate was the least stiff both in bending and torsion. The relationship between torque (T/Nm) and axial pressure (F/N) was F = 233.5T.Conclusion: The axial compressive design of ACE enhances primary stability and facilitates osseointegration, which provides an alternative option of metaphyseal fixation for endoprosthetic reconstruction.

Abstract Background Adequate margins are technically difficult to achieve for malignant tumors involving the sacroiliac joint due to limited accessibility and viewing window. In order to address the technical difficulties faced in iliosacral tumor resection, we proposed a technique for precise osteotomy, which involved the use of canulated screws and Gigli saw (CSGS) that facilitated directional control, anteroposterior linkage of resection points and adequate surgical margins. The purpose of the current study was to evaluate whether CSGS technique facilitated sagittal osteotomy at sacral side, and were adequate surgical margins achieved? Also functional and oncological outcomes was determined along with the noteworthy complications. Methods From April 2018 to November 2019, we retrospectively reviewed 15 patients who underwent resections for primary tumors of pelvis or sacrum necessitating iliosacral joint removal using the proposed CSGS technique. Chondrosarcoma was the most common diagnosis. The osteotomy site within sacrum was at ipsilateral ventral sacral foramina in 8 cases, midline of sacrum in 5 cases, and contralateral ventral sacral foramina and sacral ala with 1 case each. The average intraoperative blood loss was 3640 mL (range, 1200 and 6000 mL) with a mean operation duration of 7.4 hours (range, 5 to 12 hours). The mean follow-up was 23.0 months (range, 18 and 39 months) for alive patients. Results Surgical margins were wide in 12 patients (80%), wide-contaminated in 1 patient (6.7%), and marginal in 2 patients (13.3%). R0 resection was achieved in 12 (80%) patients and R1 resection in 3 patients. There were three local recurrences (20%) occurred at a mean time of 11 months postoperatively. No local recurrence was observed at sacral osteotomy. The overall one-year and three-year survival rate was 86.7% and 72.7% respectively.Complications occurred in three patients. Conclusions The current study demonstrated that CSGS technique for tumor resection within the sacrum and pelvis was feasible and can achieve ideal resection accuracies. The use of CSGS was associated with high likelihood of negative margin resections in the current series. Intraoperative use of CSGS appeared to be technically straightforward and allowed achievement of planned surgical margins. It is worthwhile to consider the use of CSGS technique in resection of pelvic tumors with sacral invasion and iliosacral tumors, however further follow-up at mid to long-term is warranted to observe local recurrence rate.

Abstract Nuclear astrophysics is an interdisciplinary research field of nuclear physics and astrophysics, seeking for the answer to a question, how to understand the evolution of the universe with the nuclear processes which we learn. We review the research activities of nuclear astrophysics in east and southeast Asia which includes astronomy, experimental and theoretical nuclear physics, and astrophysics. Several hot topics such as the Li problems, critical nuclear reactions and properties in stars, properties of dense matter, r-process nucleosynthesis, and ν-process nucleosynthesis are chosen and discussed in further details. Some future Asian facilities, together with physics perspectives, are introduced.

Abstract Background and objectives Treatment of benign osteolytic lesions in the femoral head and neck can be extremely challenging, particularly in children with open physis or for aggressive tumors with pathological fracture. There remains the difficult management decision as to whether to perform complete excision of the involved area or only curettage. Moreover, there is no agreed consensus on the optimal approach to lesion access when performing curettage, which included the transcervical, open and direct approach. The current systematic review aims to provide guidance for selection of surgical methods in clinical practice by comparing the advantages and drawbacks of different procedures. Methods A comprehensive literature search of PubMed, Embase and Web of Science databases were executed for human studies restricted to the English language. The search was filtered to include studies published from January 1980 to January 2020. Results A total of 33 articles including 274 patients were enrolled in the final analysis. The most common diagnosis was chondroblastoma (CBT) (104, 38.0%), followed by giant cell tumor (GCT) (56, 20.4%). There were 57 (20.8%) patients with pathological fracture. Intralesional curettage was performed in 257 (93.8%) patients with the local recurrence of 12.5% at the mean follow-up of 51.5 months. The patients who were presented with open physis or curetted via transcervical approach developed higher local recurrence in patients with CBT (P

Cytokinin is an important endogenous hormone in plants performing a wide spectrum of biological roles. The type-A response regulators (RRAs) are primary cytokinin response genes, which are important components of the cytokinin signaling pathway and are involved in the regulation of plant growth and development. By analysis of the whole genome sequence of wheat, we identified 20 genes encoding RRAs which were clustered into eight homologous groups. The gene structure, conserved motifs, chromosomal location, and cis-acting regulatory elements of the TaRRAs were analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of most of the TaRRAs increased rapidly on exogenous cytokinin application. Moreover, the TaRRA family members displayed different expression profiles under the stress treatments of drought, salt, cold, and heat. This study provides valuable insights into the RRA gene family in wheat and promotes the potential application of these genes in wheat genetic improvement.

Abstract Background Treatments for metastatic fracture of the humeral shaft continue to evolve as advances are made in both oncological and operative management. The purposes of this study were to critically evaluate the effectiveness of intercalary endoprostheses in treating metastatic humeral shaft fractures and to clarify the surgical indications for this technique. Methods Sixty-three patients treated surgically for 66 metastatic fractures of the humerus shaft were retrospectively reviewed. Intramedullary nailing (IMN) was performed in 16 lesions, plate fixation (PF) in 33 lesions, and prosthetic replacement in 17 lesions. The operative time, intraoperative blood loss, and postoperative complications were noted. The function of the upper extremities was assessed by the Musculoskeletal Tumor Society (MSTS) score and American Shoulder and Elbow Surgeons (ASES) score. All included patients were followed until reconstructive failure or death. Results The operative time was relatively shorter in the prosthesis group than in either the IMN group (p = 0.169) or PF group (p = 0.002). Notably, intraoperative blood loss was significantly less in the prosthesis group than in either the IMN group (p = 0.03) or PF group (p = 0.012). The average follow-up time was 20.3 (range, 3–75) months, and the overall survival rate was 59.7% at 12 months and 46.7% at 24 months. One rotator cuff injury, 3 cases of iatrogenic radial nerve palsy, 5 cases of local tumor progression, and 1 mechanical failure occurred in the osteosynthesis group, whereas one case of aseptic loosening of the distal stem and one case of local relapse were observed in the prosthesis group. There were no significant differences in functional scores among the three groups. Conclusions Intercalary prosthetic replacement of the humeral shaft may be a reliable solution for pathologic fractures patients; it is indicated for lesions with substantial bone loss, or accompanied soft tissue mass, or for those patients with better prognosis.

Objective To evaluate preliminary results of a 3D‐printed modular prosthesis for spinal reconstruction after multilevel thoracolumbar total en bloc spondylectomy (TES). Methods Patients with thoracolumbar spinal tumors treated surgically between January 2016 and April 2019 were included in this retrospective study. A total of 17 male and 10 female patients with a mean age of 42 (range, 15–72) years comprised the sample. The pathological diagnoses included six chondrosarcomas (one of them was mesenchymal chondrosarcoma), six giant cell tumors, three malignant peripheral nerve sheath tumors, two osteosarcomas, two undifferentiated high‐grade pleomorphic sarcomas (UPS), two solitary fibrous tumors, one Ewing's sarcoma, one liposarcoma, and four metastatic tumors. Tumors involved 2 levels in 14 patients, 3 levels in seven patients, 4 levels in four patients, 5 levels in one patient, and 6 levels in one patient. A 3D‐printed modular prosthesis was used for anterior column reconstruction after TES. All analyses were performed using SPSS version 18.0 (SPSS, Inc., Chicago, IL). Descriptive statistics were used to analyze the demographic data and clinical outcomes. Data forms included mean, standard deviation and range. Results Under general anesthesia, all patients received TES with an average operative time of 639 (range, 210–1650) min, and the mean blood loss during operation was 4.1 (range, 0.8–13.3) L. Twenty‐two patients have been transferred to ICU for a mean time of 3.2 (range, 0–6) d. All patients had follow‐up procedures except for one, who died of perioperative complications. Mean time of follow‐up was 22 (range, 12–41) months. Local recurrence (19.2%) occurred in two patients with intralesional margin and three patients with marginal margin, respectively. At the end of follow‐up, three patients died of disease, eight patients were alive with disease, and 15 patients had no evidence of disease. Average lengths of resected vertebrae and modular prostheses were 71.4 ± 26.5 mm (range, 40–142 mm) and 68.4 ± 23.9 mm (range, 40–132 mm), respectively. In 26 patients with minimum follow‐up of more than 1 year, no evidence of internal fixation failure or dislocation of vertebral prosthesis was found. Asymptomatic prosthetic subsidence into adjacent vertebral bodies occurred in 10 patients with a mean length of 1.8 ± 1.0 mm (range, 1–4 mm). The subsidence was seen at proximal end in two patients, distal end in four patients, and both ends in four patients. Eighteen major complications and 14 minor complications were found in 15 patients. All patients fully recovered at 3 or 6 months after operation. At the latest follow‐up, in 23 alive patients, 19 can walk independently and two can achieve outdoor activities by walking aid. Conclusion For spinal reconstruction after multilevel thoracolumbar TES, 3D‐printed modular vertebral prosthesis is suitable for different length of anterior column reconstruction with less mechanical complications, and can provide a stable environment to maintain or rehabilitate patients' neurological function in short‐term follow‐up.

Abstract Background En bloc resection of malignant tumors involving upper thoracic spine is technically difficult. We surgically treated a patient with grade 2 chondrosarcoma involving T1–5, left upper thoracic cavity, and chest wall. Case presentation A 37 years old, male patient was referred to our hospital for a huge lump involved left shoulder and chest wall. In order to achieve satisfied surgical margins, anterior approach, posterior approach, and lateral approach were carried out sequentially. After en bloc tumor resection, the upper thoracic spine was reconstructed with a 3D-printed modular vertebral prosthesis, and the huge chest wall defect was repaired by a methyl methacrylate layer between 2 pieces of polypropylene mesh. Postoperatively, the patient suffered from pneumonia and neurological deterioration which fully recovered eventfully. At 24 months after operation, the vertebral prosthesis and internal fixation were intact; there was no tumor local recurrence, and the patient was alive with stable pulmonary metastases. Conclusion This case report describes resection of a huge chondrosarcoma involving not only multilevel upper thoracic spine, but also entire left upper thoracic cavity and chest wall. Although with complications, en bloc tumor resection with combined surgical approach and effective reconstructions could improve oncologic and functional prognosis in carefully selected spinal tumor patients.