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Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma in vitro and in vivo. In vitro, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively. In vivo, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. In vivo, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway in vitro and in vivo, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.
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Due to persistent inflammation and oxidative stress reactions, achieving drug absorption in diabetic wounds is challenging. To overcome this problem, our article presents a composite hydrogel, GelMA-GA/DMOG@GDNP, which consists of gelatin methacryloyl (GelMA) treated with gallic acid (GA) and encapsulating ginseng-derived nanoparticles (GDNPs) loaded with dimethyloxallyl glycine (DMOG). The composite hydrogel demonstrates excellent biocompatibility. In laboratory settings, the hydrogel inhibits the production of nitric oxide synthase 2 (iNOS) in mouse immune cells (RAW264.7 cells), enhances the growth and migration of mouse connective tissue cells (L929 cells) and human endothelial cells (HUVECs), and promotes tube formation in HUVECs. In a rat model of type 1 diabetes-induced wounds, the composite hydrogel attenuates inflammatory reactions, facilitates the formation of fibres and blood vessels, accelerates wound healing, and elucidates specific pathway mechanisms through transcriptome sequencing. Therefore, the GelMA-GA/DMOG@GDNP hydrogel can serve as a safe and efficient wound dressing to regulate the inflammatory response, promote collagen fiber and blood vessel formation, and accelerate wound healing. These findings suggest that utilizing this multifunctional engineered nanoparticle-loaded hydrogel in a clinical setting may be a promising strategy for diabetic wound healing.
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Diabetes Mellitus Experimental , Ácido Gálico , Gelatina , Nanopartículas , Panax , Cicatrização , Animais , Gelatina/química , Cicatrização/efeitos dos fármacos , Ácido Gálico/química , Ácido Gálico/farmacologia , Ratos , Nanopartículas/química , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Camundongos , Panax/química , Células RAW 264.7 , Masculino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Ratos Sprague-DawleyRESUMO
The aim was to assess conditional survival for colon mucinous adenocarcinoma (MAC) patients, and to construct nomograms to predict conditional survival probability. Survival analysis was done using conditional survival, which was defined as the probability of surviving additional y years for patients who have survived for x years. The mathematical definition was express as: CS (y|x) = S (x + y)/S (x). Cox regression analyses were used to identify prognostic factors. A nomogram is constructed to predict conditional disease-free survival (DFS) and overall survival (OS) probability according to years that already survive. A total of 179 colon MAC patients were included. The 5-year DFS was 67% after surgery, and the 5-year survival probability of patients, who already survived 1, 2, 3, and 4 years were 75%, 87%, 95%, and 98%, respectively. The 5-year OS was 73% after surgery and increased to 76%, 82%, 88%, and 92% at 1, 2, 3, and 4 years, respectively. Subgroup analyses demonstrated the superiority of conditional survival was more pronounced in advanced stages than in stage I. And pT stage, pN stage, and lymphovascular invasion were significantly associated with DFS and OS. Conditional survival nomograms were constructed to predict the 5-year conditional DFS and OS probability given survival for 1, 2, 3, 4 years after surgery. Conditional survival can provide dynamic survival probability according to years that already survive, especially for patients with advanced stages. Taking into account the years already survived accounted for, novel nomograms contributed to effectively predicting conditional survival.
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RATIONALE: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS: Diagnosis and treatment of Hu-PNS. DIAGNOSES: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.
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Ganglioneuroblastoma , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Ganglioneuroblastoma/imunologia , Ganglioneuroblastoma/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Masculino , Proteínas ELAV/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Pré-Escolar , Estudos RetrospectivosRESUMO
Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-l-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100 µM for 2 hours), SAM (50 and 100 µM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of reactive oxygen species and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/day d-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/day by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of forkhead box O3 (FOXO3a) was proved to be associated with the antisenescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases.
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Senescência Celular , Proteína Forkhead Box O3 , Células-Tronco Mesenquimais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , S-Adenosilmetionina , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Animais , Senescência Celular/efeitos dos fármacos , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , S-Adenosilmetionina/farmacologia , S-Adenosilmetionina/metabolismo , Camundongos , Diferenciação Celular/efeitos dos fármacos , Masculino , Humanos , Camundongos Endogâmicos C57BLRESUMO
The prognosis of patients with locally advanced rectal cancer (LARC) has improved with the adoption of a multidisciplinary treatment approach combining neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). Developing real-time, sensitive biomarkers to monitor systemic changes during nCRT is of paramount importance. Although the association between albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) and prognosis in various cancers is established, its prognostic value in LARC patients undergoing nCRT is not well-studied. This study enrolled a cohort of 618 LARC patients, stratifying them into two groups according to their change in Alb-dNLR (∆Alb-dNLR) values, using an optimal cut-off point: a low ∆Alb-dNLR group (≤ 0.90) and a high ∆Alb-dNLR group (> 0.90). The prognostic significance of ∆Alb-dNLR was evaluated using a Cox proportional hazards model. The 5-year overall survival (OS) rates were 75.2% in the low ∆Alb-dNLR group (≤ 0.90) and 85.9% in the high ∆Alb-dNLR group (>0.90) (P < 0.001). The 5-year disease-free survival (DFS) rates were 71.2% and 80.6%, respectively (P = 0.016). Multivariate analyses demonstrated that both ∆Alb-dNLR and pre-Alb-dNLR were independent prognostic factors for OS (P ≤ 0.001), while ∆Alb-dNLR was demonstrated as an independent prognostic factor for DFS (P = 0.016). A predictive nomogram, incorporating the ∆Alb-dNLR subgroup, demonstrated enhanced performance (concordance index [C-index] of 0.720 for OS and 0.690 for DFS) compared to the pre-treatment Alb-dNLR subgroup (C-index of 0.700 for OS and of 0.680 for DFS). Therefore, ∆Alb-dNLR shows significant potential as a usable and prognostic biomarker for predicting OS and DFS in LARC patients undergoing nCRT.
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Laparoscopia , Neoplasias Retais , Humanos , Canal Anal , Dissecação , Neoplasias Retais/cirurgiaRESUMO
BACKGROUND: No studies have investigated the role of IPI in assessing the prognosis of locally advanced rectal cancer (LARC) patients undergoing nCRT. OBJECTIVE: We attempted to combine neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (sLDH) to generate a new rectal immune prognostic index (RIPI) to explore whether RIPI is associated with LARC prognosis. We aimed to identify whether there is a population that might benefit from RIPI in LARC. METHODS: LARC patients who underwent radical surgery after Neoadjuvant chemoradiotherapy (nCRT) were enrolled between February 2012 and May 2017. Based on the best cut-off points of NLR and sLDH, we developed RIPI. The patients were grouped as follows: (1) good, RIPI = 0, good, 0 factors; (2) poor, RIPI = 1, 1 or 2 factors. RESULTS: This study enrolled 642 patients. In yp TNM stage II patients, 5-year disease-free survival (DFS) differed significantly between the RIPI = 1 and RIPI = 0 groups (p = 0.03). Five-year DFS did not differ significantly between IPI = 0 and IPI = 1 groups in ypCR, stage I, stage II, and stage III. In multivariate analysis, the significant factor predicting DFS was pre-nCRT RIPI score (p = 0.035). CONCLUSION: The pre-nCRT RIPI was closely related to the prognosis of LARC patients undergoing nCRT. Particularly, RIPI is significant in evaluating the prognosis of ypTNM stage II LARC patients who underwent radical resection after nCRT.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Prognóstico , Quimiorradioterapia , Estudos Retrospectivos , Neoplasias Retais/terapiaRESUMO
PURPOSE: To systematically assess the quality of radiomics research in giant cell tumor of bone (GCTB) and to test the feasibility of analysis at the level of radiomics feature. METHODS: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data to identify articles of GCTB radiomics until 31 July 2022. The studies were assessed by radiomics quality score (RQS), transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement, checklist for artificial intelligence in medical imaging (CLAIM), and modified quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The radiomic features selected for model development were documented. RESULTS: Nine articles were included. The average of the ideal percentage of RQS, the TRIPOD adherence rate and the CLAIM adherence rate were 26%, 56%, and 57%, respectively. The risk of bias and applicability concerns were mainly related to the index test. The shortness in external validation and open science were repeatedly emphasized. In GCTB radiomics models, the gray level co-occurrence matrix features (40%), first order features (28%), and gray-level run-length matrix features (18%) were most selected features out of all reported features. However, none of the individual feature has appeared repeatably in multiple studies. It is not possible to meta-analyze radiomics features at present. CONCLUSION: The quality of GCTB radiomics studies is suboptimal. The reporting of individual radiomics feature data is encouraged. The analysis at the level of radiomics feature has potential to generate more practicable evidence for translating radiomics into clinical application.
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Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Inteligência Artificial , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Diagnóstico por Imagem , Biomarcadores , Neoplasias Ósseas/diagnóstico por imagemRESUMO
AIMS: The reconstruction of proximal humeral defects resulting from tumor resection is challenging. The purpose of this work was to retrospectively study the functional outcomes in patients with large bone defects after the resection of proximal humeral tumors. METHODS: We performed a retrospective analysis of 49 patients with malignant or aggressive benign tumors in the proximal humerus at our institution between 2010 and 2021. Forty-nine patients were included in the study (prosthetic replacement, n = 27; shoulder arthrodesis, n = 22). The mean follow-up was 52.8 months (range, 14-129 months). The factors evaluated included the Musculoskeletal Tumor Society (MSTS) functional score, Constant Murley Score (CMS), and complications. RESULTS: Of the 49 patients enrolled in the study, 35 were disease-free by the time of the latest follow-up, and 14 died because of the disease. Adjuvant therapies and medical comorbidities were similar between the two groups. Osteosarcoma was the most common abnormality among all the patients. The mean MSTS scores for surviving patients in the prosthesis and arthrodesis groups were 57.4% and 80.9%, respectively. The mean CMS score for the surviving patients in the prosthesis group was 43.47, and it was 61.44 for arthrodesis cases. Patients with shoulder arthrodesis demonstrated evidence of bony union at a mean of 4.5 months. CONCLUSIONS: Shoulder arthrodesis is a reliable reconstructive procedure in patients with large bone defects after the resection of proximal humeral tumors for pediatric osteosarcoma patients. Moreover, prosthetic replacement with anatomical implants results in poor function in older metastasis patients with large bone defects and resection of the deltoid muscle.
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Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.
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Autofagia , Neoplasias Ósseas , Antagonistas dos Receptores Histamínicos H1 , Osteossarcoma , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Osteossarcoma/tratamento farmacológico , Transdução de Sinais , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêuticoRESUMO
PURPOSE: The aim of this retrospective study is to evaluate the impact on efficacy and safety between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) alone and in combination with Shenqi Fuzheng injection (SFI) in patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) activating mutations. METHODS: Retrospectively, information of 88 patients receiving EGFR-TKIs as first-line targeted treatment or in combination with SFI in the Affiliated Drum Tower Hospital of Nanjing University Medical College and the Affiliated Cancer Hospital of Anhui University of Science and Technology was collected. The primary endpoint was to assess progression-free survival (PFS) and safety of EGFR-TKIs alone or in combination with SFI. RESULTS: Between January 2016 and December 2019, a total of 88 patients were enrolled in this research, including 50 cases in the EGFR-TKIs single agent therapy group and 38 cases in the SFI combined with EGFR-TKIs targeted-therapy group. The median PFS (mPFS) of monotherapy group was 10.50 months (95%CI 9.81-11.19), and 14.30 months (95%CI 10.22-18.38) in the combination therapy group. Compared to the single EGFR-TKIs administration, combinational regimen with SFI exhibited a lower incidence of rash and diarrhea in patients and was even better tolerated. CONCLUSIONS: SFI combined with the first-generation EGFR-TKIs are more efficient, can prominently prolong the PFS and attenuate the adverse reactions in patients with advanced NSCLC with EGFR-sensitive mutations.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Estudos Retrospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Receptores ErbBRESUMO
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1É expression to enhance the activities of VEGF and SDF-1É, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1É-VEGF/SDF-1É pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Fatores de Diferenciação de Crescimento , Cicatrização , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Quimiocina CXCL12/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fatores de Diferenciação de Crescimento/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
BACKGROUND: Multiple myeloma (MM) complicated with extramedullary disease (EMD) has a poor prognosis and is a limiting factor in the treatment of MM, and no standard treatment is recommended in international guidelines. Few studies have reported MM with periorbital EMD. CASE SUMMARY: In this paper, the clinical characteristics and survival of seven patients with multiple myeloma and orbital are described and analyzed. The common ocular symptoms were blurred vision, proptosis and/or eye movement disorders, IgG type MM may be a risk factor for orbital involvement. Of them, six patients were treated with bortezomib-based regimens. The median overall survival (OS) and progression free survival for the entire cohort were 48 and 33 mo, respectively, which was much worse than the OS reported for MM patients without orbital EMD. CONCLUSION: Orbital MM may have significantly shortened survival for the entire cohort, so multidisciplinary collaboration is emphasized and recommended in the diagnosis and treatment of these difficult cases.
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This study aimed to evaluate the clinical outcomes and complications of reconstruction with a composite free fibula inside other biological grafts. We retrospectively reviewed 26 patients who underwent reconstruction after bone tumor resection of the diaphysis of the long bone. Surgical data, time to bony union, functional outcomes, and complications were evaluated in all cases. The median follow-up was 72.5 months. The limb salvage rate was 100%. Primary osseous union was achieved in 90.4% of the junctions. The union rates at the metaphyseal and diaphyseal junctions were 100% and 85.7%, respectively (p = 0.255). The mean time of bony union in the upper (87.5%) and lower (91.7%) extremity was 4.6 ± 1.6 months and 6.9 ± 2 months, respectively. The mean MSTS score was 27.2 ± 3.2, with a mean MSTS rating of 90.7%. Complications occurred in 15.4% of the cases. The administration of vascularized or non-vascularized grafts did not significantly influence the union time (p = 0.875), functional outcome (p = 0.501), or blood loss (p = 0.189), but showed differences in operation time (p = 0.012) in lower extremity reconstruction. A composite free fibula inside other biological grafts provides a reasonable and durable option for osseous oncologic reconstruction of the long bone diaphysis of the extremities with an acceptable rate of complications. A higher union rate was achieved after secondary bone grafting. In lower-extremity reconstruction, two plates may be considered a better option for internal fixation. Vascularizing the fibula did not significantly affect the union time.
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Mucormycosis caused by Lichtheimia ramosa is an emerging and uncommon opportunistic infection in patients with hematological malignancies, with high mortality rates. Herein, we first report a case of pulmonary mucormycosis with Lichtheimia ramosa in a 3-year-old girl recently diagnosed with B-cell acute lymphoblastic leukemia. The diagnosis was made using computerized tomography of the lung, metagenomic next-generation sequencing (mNGS) of blood and sputum specimens, and microscopic examination to detect the development of Lichtheimia ramosa on the surgical specimen. She was effectively treated after receiving prompt treatment with amphotericin B and posaconazole, followed by aggressive surgical debridement. In our case, the fungal isolates were identified as Lichtheimia ramosa using mNGS, which assisted clinicians in quickly and accurately diagnosing and initiating early intensive treatment. This case also indicated the importance of strong clinical suspicion, as well as aggressive antifungal therapy combined with surgical debridement of affected tissues.
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OBJECTIVE: To update the systematic review of radiomics in osteosarcoma. METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data were searched to identify articles on osteosarcoma radiomics until May 15, 2022. The studies were assessed by Radiomics Quality Score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), and modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The evidence supporting radiomics application for osteosarcoma was rated according to meta-analysis results. RESULTS: Twenty-nine articles were included. The average of the ideal percentage of RQS, the TRIPOD adherence rate and the CLAIM adherence rate were 29.2%, 59.2%, and 63.7%, respectively. RQS identified a radiomics-specific issue of phantom study. TRIPOD addressed deficiency in blindness of assessment. CLAIM and TRIPOD both pointed out shortness in missing data handling and sample size or power calculation. CLAIM identified extra disadvantages in data de-identification and failure analysis. External validation and open science were emphasized by all the above three tools. The risk of bias and applicability concerns were mainly related to the index test. The meta-analysis of radiomics predicting neoadjuvant chemotherapy response by MRI presented a diagnostic odds ratio (95% confidence interval) of 28.83 (10.27-80.95) on testing datasets and was rated as weak evidence. CONCLUSIONS: The quality of osteosarcoma radiomics studies is insufficient. More investigation is needed before using radiomics to optimize osteosarcoma treatment. CLAIM is recommended to guide the design and reporting of radiomics research.
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The formation of polymeric micro-patterns on various substrates via a photolithography procedure has been widely used in semiconductor fabrication. Standard polymer patterns are usually fabricated via photosensitive polymer varnishes, in which large amounts of potentially harmful solvents with weight ratios over 50 wt% have to be removed. In the current work, a novel pattern-formation methodology via solvent-free electrospun photosensitive polymeric fibrous membranes (NFMs) instead of the conventional photosensitive solutions as the starting photoresists was proposed and practiced. For this purpose, a series of preimidized negative auto-photosensitive polyimide (PSPI) resins were first prepared via the two-step chemical imidization procedure from the copolymerization reactions of 3,3',4,4'-benzophenonetetracarboxylic- dianhydride (BTDA) and two ortho-methyl-substituted aromatic diamines, including 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane (TMMDA) and 3,7-diamino-2,8-dimethyl- dibenzothiophene sulfone (TSN). The derived homopolymer PI-1 (BTDA-TMMDA) and the copolymers, including SPI-2~SPI-6, with the molar ratio of 5~25% for TSN in the diamine units, showed good solubility in polar solvents. Then, a series of PSPI NFMs were fabricated via standard electrospinning procedure with the developed PSPI solutions in N,N-dimethylacetamide (DMAc) with a solid content of 25 wt% as the starting materials. The derived PSPI NFMs showed good thermal stability with 5% weight loss temperatures higher than 500 °C in nitrogen. Meanwhile, the derived PSPIs showed good photosensitivity to the ultraviolet (UV) emitting wavelengths of i-line (365 nm), g-line (405 nm) and h-line (436 nm) of the high-pressure mercury lamps in both forms of transparent films and opaque NFMs. Fine micro-patterns with a line width of around 100 µm were directly obtained from the representative SPI-4 NFM via standard photolithography procedure.