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ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

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Antivirais , Medicamentos de Ervas Chinesas , Óleos Voláteis , Infecções por Orthomyxoviridae , Animais , Óleos Voláteis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Antivirais/farmacologia , Camundongos Endogâmicos BALB C , Pneumonia Viral/tratamento farmacológico , Masculino , Células Madin Darby de Rim Canino , Cães , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pulmão/metabolismo , Humanos , Feminino , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia/metabolismo

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Background: Soft tissue sarcoma (STS) are heterogeneous and rare tumors, and few studies have explored predicting the prognosis of patients with STS. The Lung Immune Prognostic Index (LIPI), calculated based on baseline serum lactate dehydrogenase (LDH) and the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), was considered effective in predicting the prognosis of patients with pulmonary cancer and other malignancies. However, the efficacy of the LIPI in predicting the prognosis of patients with STS remains unclear. Methods: This study retrospectively reviewed patients with STS admitted to our center from January 2016 to January 2021. Their hematological and clinical characteristics were collected and analyzed to construct the LIPI specific to STS. The correlations between various predictive factors and overall survival (OS) were examined using Kaplan-Meier and Cox regression analyses. Independent risk factors for OS were identified using univariate and multivariate analyses. Finally, a LIPI nomogram model for STS was established. Results: This study enrolled 302 patients with STS, of which 87 (28.9%), 162 (53.6%), and 53 (17.5%) were classified into three LIPI-based categories: good, moderate, and poor, respectively (P < 0.0001). The time-dependent operator curve showed that the LIPI had better prognostic predictive ability than other hematological and clinical characteristics. Univariate and multivariate analyses identified the Fédération Nationale des Centres de Lutte Contre le Cancer grade (FNCLCC/G), tumor size, and LIPI as independent risk factors. Finally, a nomogram was constructed by integrating the significant prognostic factors. Its C-index was 0.72, and the calibration curve indicated that it could accurately predict the three- and five-year OS of patients with STS. The decision and clinical impact curves also indicated that implementing this LIPI-nomogram could significantly benefit patients with STS. Conclusion: This study explored the efficacy of the LIPI in predicting the prognosis of 302 patients with STS, classifying them into three categories to evaluate the prognosis. It also reconstructed a LIPI-based nomogram to assist clinicians in predicting the three- and five-year OS of patients with STS, potentially enabling timely intervention and customized management.

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OBJECTIVE: Periacetabular tumors, especially in young to middle-aged patients with invasive benign tumors or low-grade malignant tumors involving type II or II + III, present significant challenges due to their rarity and the complexity of the anatomical and biomechanical structures involved. The primary difficulty lies in balancing the need to avoid unfavorable oncological outcomes while maintaining postoperative hip joint function during surgical resection. This study aimed to evaluate the effectiveness and reliability of a surgical method involving partial weight-bearing acetabular preservation combined with the use of an uncontaminated femoral head autograft to reconstruct the segmental bone defect after intra-articular resection of the tumorous joint, providing a solution that ensures both oncological safety and functional preservation of the hip joint in these patients. METHODS: We conducted a retrospective study with a follow-up period of at least 36 months. From January 2010 to October 2020, we reviewed 20 cases of patients under 60 year of age with periacetabular invasive benign tumors or primary low-grade malignant tumors. All patients underwent reconstruction of the tumorous joint using autologous femoral head grafts. Data collected included patient age, gender, tumor type, preoperative and postoperative visual analog scale (VAS) scores, Musculoskeletal Tumor Society (MSTS) scores, Harris Hip Scores (HHS), patient survival rates, postoperative tumor recurrence, and surgical complications. To analyze the data, we utilized various statistical methods, including descriptive statistics to summarize patient demographics and clinical characteristics, and paired sample t-tests to compare preoperative and postoperative scores. RESULTS: The study included 20 patients, and a total median follow-up was 83 months. Their pathologic diagnoses comprised 13 giant cell tumors (GCTs), 5 chondrosarcomas, one chondroblastoma, and 1 leiomyosarcoma. Postoperatively, the median differences in vertical and horizontal center of rotation (COR) were 3.8 and 4.0 mm. Median limb length discrepancy (LLD) postoperatively was 5.7 mm (range, 2.3-17.8 mm). Two patients (10%) experienced delayed wound healing, resolved with antibiotics and early surgical debridement. One patient experienced dislocation 3 months postoperatively, which was promptly addressed under general anesthesia without further dislocation. CONCLUSION: Through multiplanar osteotomy with limited margins, femoral head autograft, and uncemented total hip replacement for pelvic segmental bone defects in selected patients in type II or II + III appears to be an encouraging limb-sparing surgery worthy of consideration for carefully selected patients.

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Background: Involvement of the distal fibula by alveolar soft-part sarcoma is rare. Extensive resection or amputation may be needed; however, distal fibula resection can disrupt foot and ankle biomechanics, leading to ankle joint instability. Reports on joint preservation for maintaining optimal ankle joint function are scarce. Computer-aided design and individualized three-dimensional (3D)-printed uncemented implants represent an evolving solution for reconstructing the distal fibula. Case presentation: A 34-year-old woman was diagnosed with alveolar soft-part sarcoma in the right lower leg involving the cortical bone of the fibula. After anlotinib treatment, the tumor size decreased, and the tumor response rate was a partial response (PR); however, the patient continued to experience adverse reactions. With multiple disciplinary team discussions, surgical resection was deemed appropriate. Due to the extensive defect and ankle joint instability after resection, a custom-made 3D-printed prosthesis was designed and fabricated to reconstruct the defect, preserving the lateral malleolus. During the follow-up, the patient achieved favorable ankle function, and no prosthesis-related complications were observed. Conclusion: 3D-printed personalized uncemented implants constitute a novel approach and method for addressing the reconstruction issues of the distal fibula and ankle joint. Through the personalized design of 3D-printed prostheses, the lateral malleolus can be preserved, ensuring the normal anatomical structure of the ankle joint. They achieve a well-integrated interface between the prosthesis and bone, ensuring satisfactory postoperative function. Additionally, they offer valuable insights for reconstructing distal bone defects near joints in the extremities. However, confirming these findings requires extensive cohort studies.

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[This corrects the article DOI: 10.1016/j.heliyon.2024.e32963.].

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Aims: Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes. Methods: This study involved patients who underwent implantation of an uncemented distal femoral endoprosthesis with a short and curved stem between 2014 and 2019. Functional outcomes were assessed using the 1993 version of the Musculoskeletal Tumour Society (MSTS-93) score. Additionally, we quantified five types of complications and assessed osseointegration radiologically. The survivorship of the endoprosthesis was evaluated according to two endpoints. A total of 134 patients with a median age of 26 years (IQR 16 to 41) were included in our study. The median follow-up time was 61 months (IQR 56 to 76), and the median functional MSTS-93 was 83% (IQR 73 to 91) postoperatively. Results: Overall, 21 patients (16%) encountered complications, and the rate of aseptic loosening was 7% (9/134). The survival rate up to 8.5 years was 93% for aseptic loosening as the endpoint, and 88% for any reason as the endpoint, retrospectively. Conclusion: The use of an uncemented distal femoral endoprosthesis with a short, curved stem demonstrated a low incidence of aseptic loosening and achieved long-term survivorship of up to nine years. Meanwhile, aseptic loosening typically occurs in the early stage postoperatively.

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Neoplasias Femorais , Complicações Pós-Operatórias , Desenho de Prótese , Falha de Prótese , Humanos , Adulto , Masculino , Feminino , Adolescente , Neoplasias Femorais/cirurgia , Adulto Jovem , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Implantação de Prótese/métodos , Fêmur/cirurgia , Neoplasias Ósseas/cirurgia , Resultado do Tratamento , Pessoa de Meia-Idade

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Objective: To explore the causal relationships between 91 circulating inflammatory cytokines and sarcopenia-related traits (low hand grip strength, appendicular lean mass, and usual walking pace) by Mendelian randomized analysis. Methods: Independent genetic variations of inflammatory cytokines and sarcopenia-related traits were selected as instrumental variables from publicly available genome-wide association studies (GWAS). The MR analysis was primarily conducted using the inverse variance-weighted (IVW) method. Sensitivity analyses included Steiger filtering and MR PRESSO, with additional assessments for heterogeneity and pleiotropy. Results: The IVW method indicated a causal relationship between Vascular Endothelial Growth Factor A (VEGF-A) and low hand grip strength (OR = 1.05654, 95% CI: 1.02453 to 1.08956, P = 0.00046). Additionally, Tumor Necrosis Factor-beta (TNF-ß) was found to have a causal relationship with appendicular lean mass (ALM) (ß = 0.04255, 95% CI: 0.02838 to 0.05672, P = 3.96E-09). There was no evidence suggesting a significant causal relationship between inflammatory cytokines and usual walking pace. Conclusion: Our research substantiated the causal association between inflammatory cytokines, such as VEGF-A and TNF-ß, and sarcopenia. This finding may provide new avenues for future clinical treatments.

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The sustainable advancement of agriculture stands as the fundamental cornerstone of sustainable human progress. This study introduces a data-centric methodological framework founded upon the holistic delineation of measurement, feature assessment, and pathway enhancement for agricultural sustainability. Initially, the research articulates a comprehensive evaluative schema incorporating sub-dimensions encompassing agricultural production, agricultural economics, the agricultural resource environment, and rural society, grounded in sustainable development theory. Subsequently, it devises a methodological apparatus for assessing and enhancing sustainable development capabilities, employing entropy evaluation methods and exploratory spatial data analysis techniques. Employing North Anhui as a case study, the viability of this approach is substantiated. The empirical inquiry conducted within this article operationalizes comprehensive evaluation and explores pathways for optimizing agricultural sustainability, focusing on the period spanning 2011 to 2020 in Northern Anhui. The findings affirm the feasibility and efficacy of the data-driven approach. Recommendations derived from the empirical exploration of agricultural sustainability pathways at the local level offer valuable insights for governmental authorities and policymakers. This research endeavor could be extrapolated to other geographical locales worldwide, fostering innovative strides in the sustainable development of regional agriculture.

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BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive decline. To date, the specific dysfunction in the brain's hierarchical structure in AD remains unclear. METHODS: We introduced the structural decoupling index (SDI), based on a multi-site data set comprising functional and diffusion-weighted magnetic resonance imaging data from 793 subjects, to assess their brain hierarchy. RESULTS: Compared to normal controls (NCs), individuals with AD exhibited increased SDI within the posterior superior temporal sulcus, insular gyrus, precuneus, hippocampus, amygdala, postcentral gyrus, and cingulate gyrus; meanwhile, the patients with AD demonstrated decreased SDI in the frontal lobe. The SDI in those regions also showed a significant correlation with cognitive ability. Moreover, the SDI was a robust AD neuroimaging biomarker capable of accurately distinguishing diagnostic status (area under the curve [AUC] = 0.86). DISCUSSION: Our findings revealed the dysfunction of the brain's hierarchical structure in AD. Furthermore, the SDI could serve as a promising neuroimaging biomarker for AD. HIGHLIGHTS: This study utilized multi-center, multi-modal data from East Asian populations. We found an increased spatial gradient of the structure decoupling index (SDI) from sensory-motor to higher-order cognitive regions. Changes in SDI are associated with energy metabolism and mitochondria. SDI can identify Alzheimer's disease (AD) and further uncover the disease mechanisms of AD.

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Bone tissue engineering has emerged as a pivotal field addressing the critical clinical needs of bone fractures. This study focused on developing multi-composite hydrogels by synergizing biocompatible GelMA macromolecules with synthetic PEGDA and reinforcing them with nanosilicates (SN). The incorporation of SN introduces crucial trace elements such as silicon, magnesium, and lithium, promoting both angiogenesis and osteogenesis. Characterizations revealed that PEGDA significantly reinforced the composite hydrogels' stability, while SN further enhanced the mechanical integrity of the GelMA-PEGDA-SN (GPS) hydrogels. Cell studies designated that GPS improved cell proliferation and migration, angiogenic VEGF/eNOS expression and osteogenic differentiation. In vivo experiments showed that GPS hydrogels effectively enhanced calvarial bone healing, with the GPS-2 formulation (2 % SN) displaying superior bone coverage and increased vascular formation. Assessments of osteogenic formation and the angiogenic marker CD31 validated the comprehensive bone regeneration potential of GPS hydrogels. These findings highlight the significant promise of GPS hydrogels in fostering bone healing with promoted angiogenesis.

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Angiogênese , Regeneração Óssea , Hidrogéis , Osteogênese , Polietilenoglicóis , Animais , Humanos , Camundongos , Angiogênese/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Osteogênese/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Silicatos/química , Silicatos/farmacologia , Engenharia Tecidual/métodos

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OBJECTIVE: Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D-printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. METHODS: This retrospective study involved seven patients who received 3D-printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom-made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. RESULTS: The average follow-up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow-up. The HHS improved from 44 (range: 33-53) before the operation to 88 (range: 79-93) at the final follow-up. Postoperative X-rays showed that the 3D-printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis-Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow-up period, including loosening, dislocation, or component protrusion. CONCLUSION: The implantation of 3D-printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short-term follow-up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.

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Acetábulo , Artroplastia de Quadril , Prótese de Quadril , Impressão Tridimensional , Desenho de Prótese , Humanos , Artroplastia de Quadril/métodos , Acetábulo/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Porosidade , Estudos de Viabilidade

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OBJECTIVE: This study aimed to assess the correlation between the spontaneous nystagmus (SN) and the subjective visual vertical/horizontal (SVV/SVH) among patients with vestibular neuritis (VN) at the different head positions. STUDY DESIGN: Case-control study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine. METHODS: This study evaluated the SVV/SVH in both healthy subjects and patients with VN. These evaluations were performed in 5 different head positions: upright, 45° tilt to the left, 90° tilt to the left, 45° tilt to the right, and 90° tilt to the right. Additionally, the intensity of SN, as measured by slow-phase velocity, was recorded. RESULTS: In patients with VN, a significant correlation was observed between SN and SVV/SVH in an upright position. The intensity of SN was higher when the head was tilted 90° toward the affected side compared to other positions. The SVV/SVH displayed an ipsiversive shift, when the head was tilted toward both the lesion and unaffected sides, exhibiting a contraversive direction. Furthermore, the changes in position-induced SN were consistent with the displacements of SVV and SVH caused by head tilt. CONCLUSION: The presence of SN in patients with VN was observed to vary across different head position. These variations could potentially be attributed to the diverse activation patterns of the mechanical properties of otolith organs that are induced by head tilts.

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Nistagmo Patológico , Neuronite Vestibular , Humanos , Neuronite Vestibular/fisiopatologia , Neuronite Vestibular/complicações , Masculino , Feminino , Estudos de Casos e Controles , Nistagmo Patológico/fisiopatologia , Adulto , Pessoa de Meia-Idade , Gravitação , Idoso

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The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

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Medo , Corpos Geniculados , Camundongos Endogâmicos C57BL , Colículos Superiores , Vias Visuais , Animais , Masculino , Medo/fisiologia , Camundongos , Corpos Geniculados/fisiologia , Colículos Superiores/fisiologia , Vias Visuais/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Neurônios/fisiologia , Córtex Visual Primário/fisiologia , Percepção Visual/fisiologia , Comportamento Animal/fisiologia

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PURPOSE: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation. METHODS: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented. RESULTS: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up. CONCLUSION: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation.

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BACKGROUND: Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone transplant while their shortcomings limited the clinical application. Three-dimensional (3D) printed total talus prosthesis in talus lesion was reported as a useful method to reconstruct talus, however, most researches are case reports and its clinical effect remains unclear. Therefore, the current study was to explore the application of 3D printed custom-made modular prosthesis in talus malignant tumor. METHODS: We retrospectively analyzed the patients who received the 3D printed custom-made modular prosthesis treatment due to talus malignant tumor in our hospital from February 2016 to December 2021. The patient's clinical data such as oncology outcome, operation time, and volume of blood loss were recorded. The limb function was evaluated with the Musculoskeletal Tumor Society 93 (MSTS-93) score, The American Orthopedic Foot and Ankle Society (AOFAS) score; the ankle joint ranges of motion as well as the leg length discrepancy were evaluated. Plain radiography and Tomosynthesis-Shimadzu Metal Artefact Reduction Technology (T-SMART) were used to evaluate the position of prosthesis and the osseointegration. Postoperative complications were recorded. RESULTS: The average patients' age and the follow-up period were respectively 31.5 ± 13.1 years; and 54.8 months (range 26-72). The medium operation time was 2.4 ± 0.5 h; the intraoperative blood loss was 131.7 ± 121.4 ml. The mean MSTS-93 and AOFAS score was 26.8 and 88.5 respectively. The average plantar flexion, dorsiflexion, varus, and valgus were 32.5, 9.2, 10.8, and 5.8 degree respectively. One patient had delayed postoperative wound healing. There was no leg length discrepancy observed in any patient and good osseointegration was observed on the interface between the bone and talus prosthesis in all subjects. CONCLUSION: The modular structure of the prosthesis developed in this study seems to be convenient for prosthesis implantation and screws distribution. And the combination of solid and porous structure improves the initial stability and promotes bone integration. Therefore, 3D printed custom-made modular talus prosthesis could be an alternative option for talus reconstruction in talus malignant tumor patients.

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Neoplasias Ósseas , Impressão Tridimensional , Desenho de Prótese , Tálus , Humanos , Tálus/cirurgia , Tálus/diagnóstico por imagem , Masculino , Adulto , Feminino , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Implantação de Prótese/métodos , Implantação de Prótese/instrumentação , Adolescente , Articulação do Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Osseointegração , Resultado do Tratamento , Amplitude de Movimento Articular , Próteses e Implantes

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Introduction: Desmoid fibromatosis is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Targeted therapy for Desmoid fibromatosis represents a novel avenue in systemic treatment. Anlotinib, a novel multitargeted angiogenesis inhibitor, represents a novel approach for targeted therapy. Therefore, this study aims to assess the efficacy and safety of anlotinib in patients with Desmoid fibromatosis. Methods: We retrospectively gathered the clinical medical records of Desmoid fibromatosis patients who underwent anlotinib treatment between June 2019 and November 2023 at our center. Anlotinib was initiated at a daily dose of 12 mg and adjusted based on drug-related toxicity. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival served as the primary endpoint and was analyzed utilizing the Kaplan-Meier method. Results: In total, sixty-six consecutive patients were enrolled. No patients achieved a complete response; however, fourteen patients (21.21%) exhibited a partial response, while forty-six patients (70%) experienced disease stability. Progressive disease was observed in 6 patients (9.10%), and the progression-free survival rates at 12 and 36months were 89.71% and 82.81%, respectively. The disease control rate was 90.91%, while the objective response rate was 21.21%. Conclusion: Anlotinib proves effective in managing recurrent and symptomatic patients with Desmoid fibromatosis. However, the toxicity profile of anlotinib presents a higher risk of Hand-Foot Skin Reaction and hypertension. Therefore, given that 41.67% of patients were subjected to dose adjustments associated with the initial dose of 12 mg, implementing dosage reductions may help balance efficacy with side effects.

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Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

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Neoplasias Ósseas , Raios Infravermelhos , Terapia Fototérmica , Humanos , Neoplasias Ósseas/terapia , Terapia Fototérmica/métodos , Raios Infravermelhos/uso terapêutico , Animais , Fármacos Fotossensibilizantes/uso terapêutico , Osteossarcoma/terapia , Osteossarcoma/patologia , Terapia Combinada/métodos , Imunoterapia/métodos , Fotoquimioterapia/métodos , Regeneração Óssea

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OBJECTIVE: This study aims to biomimetic design a new 3D-printed lattice hemipelvis prosthesis and evaluate its clinical efficiency for pelvic reconstruction following tumor resection, focusing on feasibility, osseointegration, and patient outcomes. METHODS: From May 2020 to October 2021, twelve patients with pelvic tumors underwent tumor resection and subsequently received 3D-printed lattice hemipelvis prostheses for pelvic reconstruction. The prosthesis was strategically incorporated with lattice structures and solid to optimize mechanical performance and osseointegration. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. RESULTS: Multiple pore sizes were observed in irregular porous structures, with a wide distribution range (approximately 300-900 µm). The average follow-up of 34.7 months, ranging 26 from to 43 months. One patient with Ewing sarcoma died of pulmonary metastasis 33 months after surgery while others were alive at the last follow-up. Postoperative radiographs showed that the prosthesis's position was consistent with the preoperative planning. T-SMART images showed that the host bone was in close and tight contact with the prosthesis with no gaps at the interface. The average MSTS score was 21 at the last follow-up, ranging from 18 to 24. There was no complication requiring revision surgery or removal of the 3D-printed hemipelvis prosthesis, such as infection, screw breakage, and prosthesis loosening. CONCLUSION: The newly designed 3D-printed lattice hemipelvis prosthesis created multiple pore sizes with a wide distribution range and resulted in good osteointegration and favorable limb function.

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Neoplasias Ósseas , Neoplasias Pélvicas , Humanos , Desenho de Prótese , Biomimética , Titânio , Implantação de Prótese/métodos , Neoplasias Pélvicas/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Impressão Tridimensional

RESUMO

Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear. Therefore, this study was performed to assess the role of CISD1 in cisplatin-induced ototoxicity. We found that CISD1 expression was significantly increased after cisplatin treatment in both HEI-OC1 cells and cochlear HCs. Moreover, pharmacological inhibition of CISD1 with NL-1 inhibited cell apoptosis and reduced mitochondrial reactive oxygen species accumulation in HEI-OC1 cells and cochlear explants. Inhibition of CISD1 with small interfering RNA in HEI-OC1 cells had similar protective effects. Furthermore, NL-1 protected against CIHL in adult C57 mice, as evaluated by the auditory brainstem response and immunofluorescent staining. Mechanistically, RNA sequencing revealed that NL-1 attenuated CIHL via the PI3K and MAPK pathways. Most importantly, NL-1 did not interfere with the antitumor efficacy of cisplatin. In conclusion, our study revealed that targeting CISD1 with NL-1 reduced reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis via the PI3K and MAPK pathways in HEI-OC1 cell lines and mouse cochlear explants in vitro, and it protected against CIHL in adult C57 mice. Our study suggests that CISD1 may serve as a novel target for the prevention of CIHL.

Assuntos

Antineoplásicos , Perda Auditiva , Doenças Mitocondriais , Ototoxicidade , Camundongos , Animais , Cisplatino/toxicidade , Cisplatino/metabolismo , Antineoplásicos/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ototoxicidade/prevenção & controle , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Apoptose , Proteínas de Membrana/metabolismo , Proteínas de Ligação ao Ferro/farmacologia

RESUMO

The interplay between digitalization and economic development constitutes a pivotal global issue, yet empirical research on agricultural ecological efficiency in developing countries remains limited. This study initially establishes a measurement system and a comprehensive index for the level of agricultural digitalization. Subsequently, it delineates the relationship between agricultural digitalization level and agroecological efficiency using the spatial Durbin model, and ultimately explores the enhancing effect of agricultural digitalization level on agroecological efficiency using China as a case study. Research reveals that the agricultural ecological efficiency across the 31 mainland Chinese provinces demonstrates a generally linear upward trajectory, embodying both agglomeration and heterogeneity. The level of agricultural digitization exerts a significant, positive direct impact and facilitates a spatial spillover effect on agricultural ecological efficiency. Other control variables, such as financial support for agriculture and local economic development, impart a positive direct impact on regional agricultural ecological efficiency, while rural household operating income propels a positive spatial spillover effect on adjacent areas. The findings furnish guidance for developing countries to adeptly execute digital rural construction, aiming to enhance agricultural ecological efficiency amidst carbon constraints.