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PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Oligopeptídeos/química , Intervalo Livre de Doença , Processamento de Imagem Assistida por Computador , Radiômica , Niacinamida/análogos & derivadosRESUMO
We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.
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OBJECTIVES: Gallium-68 (68Ga)-labeled somatostatin analog (SSA) PET imaging has been widely used in clinical practice of neuroendocrine neoplasms (NENs). Compared with 68Ga, 18F has a great practical and economic advantage. Although a few studies have shown the characteristics of [18F] AlF-NOTA-octreotide ([18F]-OC) in healthy volunteers and small NEN patient groups, its clinical value needs further investigation. Herein, this retrospective study aimed to evaluate the diagnostic accuracy of [18F]-OC PET/CT in detecting NENs, as well as to compare it with contrast-enhanced CT/MRI. METHODS: We retrospectively reviewed the data of 93 patients who had undergone [18F]-OC PET/CT and CT or MRI scans. Of these patients, there were 45 patients with suspected NENs for diagnostic evaluation, and 48 patients with pathologically confirmed NENs for detecting metastasis or recurrence. [18F]-OC PET/CT images were evaluated visually and semi-quantitatively by measuring maximum standardized uptake value of tumor (SUVmax), tumor-to-background SUVmax ratio (TBR), and SUVmax of hypophysis (SUVhypophysis). A total of 276 suspected NEN lesions were found in these 93 patients. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. RESULTS: Forty-five patients with suspected NENs were confirmed by histopathological examination via resection or biopsy. [18F]-OC PET/CT showed high radiotracer uptake in the lesions of G1-G3 NENs. [18F]-OC PET/CT showed superior performance with 96.3% of sensitivity, 77.8% of specificity, and 88.9% of accuracy in diagnosing NENs compared to CT/MRI. When cutoffs of SUVmax, TBR, and SUVhypophysis were 8.3, 3.1, and 15.4, [18F]-OC PET/CT had the best equilibrium between sensitivity and specificity for differentiating NEN from non-NEN lesions. For a total of 276 suspected NEN lesions, the sensitivity, specificity, and accuracy of [18F]-OC PET/CT for diagnosis of NENs were 90.5%, 82.1%, and 88.8%, respectively, and were higher than those of CT and MRI. G1 and G2 NENs had higher TBR and lower CT enhancement intensity than G3. The SUVmax and TBR had a positive correlation with CT enhancement intensity in G2 rather than in G1 or G3. CONCLUSIONS: [18F]-OC PET/CT is a promising imaging modality for initial diagnosis and detecting metastasis or postoperative recurrence in NENs.
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Tumores Neuroendócrinos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Estudos Retrospectivos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Imageamento por Ressonância MagnéticaRESUMO
Clinical unpredictability and variability following fat grafting remain non-negligible problems due to the unknown mechanism of grafted fat retention. The role of the extracellular matrix (ECM), which renders cells with structural and biochemical support, has been ignored. This study aimed to clarify the ECM remodeling process, related cellular events, and the spatiotemporal relationship between ECM remodeling and adipocyte survival and adipogenesis after fat grafting. Labeled Coleman fat by the matrix-tracing technique was grafted in nude mice. The ECM remodeling process and cellular events were assessed in vivo. The related cytokines were evaluated by qRT-PCR. An in vitro cell migration assay was performed to verify the chemotactic effect of M2-like macrophages on fibroblasts. The results demonstrated that in the periphery, most of the adipocytes of the graft survived or regenerated, and the graft-derived ECM was gradually replaced by the newly-formed ECM. In the central parts, most adipocytes in the grafts died shortly after, and a small part of the graft-derived and newly-formed ECM was expressed with irregular morphology. Adipose ECM remodeling is associated with increased infiltration of macrophages and fibroblasts, as well as up-regulated expression of cytokines in the adipose tissue. To sum up, our results describe the various preservation mode of fat grafts after transplantation and underscore the importance of macrophage-mediated ECM remodeling in graft preservation after fat grafting. The appreciation and manipulation of underlying mechanisms that are operant in this setting stand to explore new therapeutic approaches and improve clinical outcomes of fat grafting.
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Tecido Adiposo , Matriz Extracelular , Animais , Citocinas , Macrófagos , Camundongos , Camundongos NusRESUMO
OBJECTIVE: We performed a comprehensive systematic review and meta-analysis comparing initiation of full solid diet (FSD) versus stepwise diet to better define the management of patients with mild acute pancreatitis (AP). METHODS: Electronic databases were searched through August 2, 2021 for trials comparing initial FSD versus stepwise advancement in patients with mild AP on length of hospital stay (LOHS). We stratified by whether diet was initiated early (within 24 h or immediately upon presence of bowel sounds). RESULTS: We identified seven RCTs that compared LOHS in AP patients who received initial oral intake with solid diet versus stepwise diet. Across the studies a total of 305 patients were randomized to immediate FSD and 308 patients to sequential advancement. Patients who were initiated on a FSD had a significant reduction in total LOHS (Standardized Mean Difference (SMD) -0.52 [95% CI -0.69, -0.36]). There was no difference in post refeeding abdominal pain, tolerance of diet, or necessity to cease diet between the two groups. Sub-analysis of three studies that initiated FSD early reduced total LOHS (OR -0.95 [95% CI -1.26, -0.65]) compared to those who received graded diet advancement as well as higher likelihood of tolerating the assigned diet (OR 6.8 [95% CI 1.2, 39.2]). CONCLUSIONS: Our meta-analysis shows that initiation of FSD reduces total LOHS in patients with mild AP and does not increase post refeeding abdominal pain. Though additional high-quality studies are needed, these findings support initial solid diet for AP and consideration of feeding within the first 24 h.
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Pancreatite , Humanos , Pancreatite/terapia , Doença Aguda , Dieta , Tempo de Internação , Dor Abdominal , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Skin filler is an option for treating skin aging and wrinkles; however, currently used fillers are limited by poor biocompatibility, rapid degradation, and possible hypersensitivity reactions. Autologous adipose tissue-derived products have been recognized as promising options for skin rejuvenation. OBJECTIVES: This study aimed to develop a novel adipose-derived product for skin filling. METHODS: Adipose collagen fragment (ACF) was prepared through pulverization, filtration, and centrifugation. The macrography, structure, types of collagen, and cell viability of ACF were evaluated by immunostaining, western blotting, and cell culture assays. ACF, nanofat, and phosphate-buffered saline (9 spots/side, 0.01 mL/spot) were intradermally injected in the dorsal skin of 36 female BALB/c nude mice; the skin filling capacity and the collagen remodeling process were then investigated. Twenty-one female patients with fine rhytides in the infraorbital areas were enrolled and received clinical applications of ACF treatment. Therapeutic effects and patients' satisfaction scores were recorded. RESULTS: The mean [standard deviation] yield of ACF from 50 mL of Coleman fat was 4.91 [0.25] mL. ACF contained nonviable cells and high levels of collagen I, collagen IV, and laminin. Fibroblasts and procollagen significantly increased in ACF and ACF-treated dermis (P < 0.05). Overall, 85.7% of patients were satisfied with the therapy results, and no infections, injection site nodules, or other unwanted side effects were observed. CONCLUSIONS: ACF significantly improved dermal thickness and collagen synthesis and may serve as a potential autologous skin filler.
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Preenchedores Dérmicos , Envelhecimento da Pele , Tecido Adiposo , Animais , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Camundongos , Camundongos NusRESUMO
BACKGROUND: Skin filler is an option for treating skin aging and wrinkles; however, currently used fillers are limited by poor biocompatibility, rapid degradation, and possible hypersensitivity reactions. Autologous adipose tissue-derived products have been recognized as promising options for skin rejuvenation. OBJECTIVES: This study aimed to develop a novel adipose-derived product for skin filling. METHODS: Adipose collagen fragment (ACF) was prepared through pulverization, filtration, and centrifugation. The macrography, structure, types of collagen, and cell viability of ACF were evaluated by immunostaining, western blotting, and cell culture assays. ACF, nanofat, and phosphate-buffered saline (9 spots/side, 0.01 mL/spot) were intradermally injected in the dorsal skin of 36 female BALB/c nude mice; the skin filling capacity and the collagen remodeling process were then investigated. Twenty-one female patients with fine rhytides in the infraorbital areas were enrolled and received clinical applications of ACF treatment. Therapeutic effects and patients' satisfaction scores were recorded. RESULTS: The mean [standard deviation] yield of ACF from 50 mL of Coleman fat was 4.91 [0.25] mL. ACF contained nonviable cells and high levels of collagen I, collagen IV, and laminin. Fibroblasts and procollagen significantly increased in ACF and ACF-treated dermis (P < 0.05). Overall, 85.7% of patients were satisfied with the therapy results, and no infections, injection site nodules, or other unwanted side effects were observed. CONCLUSIONS: ACF significantly improved dermal thickness and collagen synthesis and may serve as a potential autologous skin filler.
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Preenchedores Dérmicos , Camundongos , Animais , Feminino , Camundongos Nus , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Tecido AdiposoRESUMO
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations are common complications after allogeneic hematopoietic cell transplantation (allo-HCT), but data focusing on non-Hodgkin lymphoma (NHL) are limited. We retrospectively analyzed the prevalence of EBV and CMV reactivation post-allo-HCT and the impacts on transplant outcomes in 160 NHL patients. The 1-year incidences of EBV and CMV reactivation were 22.58% and 25.55%, respectively. Independent impactors for EBV reactivation were more than 6 lines of chemotherapy (P = 0.030), use of rituximab (P = 0.004), and neutrophil recovery within 30 days post-HCT (P = 0.022). For T-cell lymphoblastic lymphoma patients, the International Prognostic Index (IPI) (P = 0.015) and chronic GVHD (P = 0.001) increased the risk of CMV reactivation. CMV reactivation was independently related to a lower risk of relapse (P = 0.027) but higher transplant-related mortality (TRM) (P = 0.038). Although viral reactivation had no significant impact on overall survival (OS) in the whole cohort, it led to an inferior 2-year OS (67.6% versus 92.5%, P = 0.005) and TRM (20.1% versus 4.7%, P = 0.020) in recipients surviving for more than 180 days. We concluded that EBV and CMV reactivation post-allotransplant still deserved concern particularly in NHL patients with high-risk factors, since it is generally related to a deteriorated prognosis. Large-scale studies are warranted to validate our findings.
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Infecções por Citomegalovirus/etiologia , Citomegalovirus/fisiologia , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/fisiologia , Linfoma não Hodgkin/terapia , Ativação Viral , Adulto , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunoterapia Adotiva , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversosRESUMO
PURPOSE: To report a patient with chronic ocular graft versus host disease who achieved long-term stability of a descemetocele using prosthetic replacement of the ocular surface ecosystem (PROSE) treatment. METHODS: Case report and literature review. RESULTS: A 60-year-old white man, who underwent PROSE treatment 4 years earlier to address severe dry eyes secondary to ocular graft versus host disease, developed a central corneal ulcer that resulted in descemetocele formation. Because of the risks of surgical intervention in an immunocompromised patient with severe ocular surface disease, the descemetocele was monitored closely as the patient continued PROSE device wear. After 1 year with continued PROSE therapy, the patient's descemetocele remained stable without perforation and corrected visual acuity stabilized at 20/50 in the affected eye. CONCLUSIONS: This is the first case that reports stabilization of a descemetocele with a PROSE device. For patients at high risk for postsurgical complications, PROSE treatment could be considered as an alternative to corneal transplantation and as an adjunct to other ocular therapies in patients with descemetocele formation.
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Lentes de Contato , Doenças da Córnea/terapia , Lâmina Limitante Posterior/patologia , Hérnia/terapia , Doenças da Córnea/etiologia , Ecossistema , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Hérnia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Ajuste de Prótese , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Acuidade Visual/fisiologiaRESUMO
Syntaxins are a conserved family of SNARE proteins and contain C-terminal transmembrane anchors required for their membrane fusion activity. Here we show that Stx3 (syntaxin 3) unexpectedly also functions as a nuclear regulator of gene expression. We found that alternative splicing creates a soluble isoform that we termed Stx3S, lacking the transmembrane anchor. Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). Stx3S is differentially expressed in normal human tissues, during epithelial cell polarization, and in breast cancer versus normal breast tissue. Inhibition of endogenous Stx3S expression alters the expression of cancer-associated genes and promotes cell proliferation. Similar nuclear-targeted, soluble forms of other syntaxins were identified, suggesting that nuclear signaling is a conserved, novel function common among these membrane-trafficking proteins.
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Proteínas E1A de Adenovirus/metabolismo , Núcleo Celular/metabolismo , Proliferação de Células , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Qa-SNARE/metabolismo , Transdução de Sinais , beta Carioferinas/metabolismo , Proteínas E1A de Adenovirus/genética , Animais , Células COS , Células CACO-2 , Núcleo Celular/genética , Chlorocebus aethiops , Cães , Células HEK293 , Células HeLa , Humanos , Células Madin Darby de Rim Canino , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ets , Proteínas Qa-SNARE/genética , Solubilidade , beta Carioferinas/genéticaRESUMO
BACKGROUND: Advanced stage laryngeal squamous cell carcinoma (LSCC) presents a poor prognosis; thus, there is a great need to identify novel prognostic molecular markers. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is thought to be a novel prognostic factor in several cancers, but its role in LSCC remains unknown. Cancer stem cells (CSCs) are responsible for most instances of tumor recurrence and the development of drug resistance and have been proven to be present in head and neck cancers. Our preliminary study indicated that PLOD2 was elevated in LSCC tissues; therefore, we hypothesized that PLOD2 is related to the prognosis of LSCC patients and aimed to explore the role and underlying mechanism of PLOD2 in LSCC. METHODS: We validated the prognostic role of PLOD2 in 114 LSCC patients by immunohistochemistry. Stable PLOD2-overexpressing Hep-2 and FaDu cells were established and assessed by molecular biology and biochemistry methods both in vitro and in vivo. RESULTS: We confirmed that PLOD2 overexpression was correlated with poor prognosis in LSCC patients. PLOD2 overexpression strengthened the CSC-like properties of Hep-2 and FaDu cells, activated the Wnt signaling pathway and conferred drug resistance in LSCC in vitro and in vivo. CONCLUSIONS: We found that PLOD2 could serve as a prognostic marker in patients with LSCC and confer drug resistance in LSCC by increasing CSC-like traits; in addition, a Wnt-responsive CSC pathway was identified.
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Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Laríngeas/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Prognóstico , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To evaluate clinical effect and safety of floating needle therapy and duloxetine in treating patients with persistent somatoform pain disorder (PSPD). METHODS: Totally 108 PSPD patients were randomly assigned to the floating needle treatment group, the duloxetine treatment group, and the placebo treatment group, 36 in each group. Patients in the floating needle treatment group received floating needle therapy and placebo. Those in the duloxetine treatment group received duloxetine and simulated floating needle therapy. Those in the placebo treatment group received the placebo and simulated floating needle therapy. All treatment lasted for six weeks. Efficacy and adverse reactions were evaluated using Simple McGill pain scale (SF-MPQ) and Treatment Emergent Symptom Scale (TESS) before treatment and immediately after treatment, as well as at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Hamilton Depression Scale (HAMD, 17 items), Hamilton Anxiety Scale (HAMA) were assessed before treatment and at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Patients in the floating needle treatment group and the duloxetine treatment group with the total reducing score rate of SF-MPQ in Pain Rating index (PRI) ≥ 50% after 6 weeks' treatment were involved in the follow-up study. RESULTS: (1) Compared with the same group before treatment, SF-MPQ score, HAMD score and HAMA total scores all decreased in all the three groups at the end of 1st, 2nd, 4th, and 6th week of treatment (P < 0.05, P < 0.01). Besides , each item of SF-MPQ significantly decreased immediately after treatment in the floating needle treatment group (P < 0.01). Compared with the placebo treatment group, SF-MPQ, HAMD, and HAMA total score in the floating needle treatment group significantly decreased after 1, 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). SF-MPQ score, HAMD score and HAMA total score in the duloxetine treatment group also significantly decreased after 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). (2) There were 3 patients (8.3%) who had adverse reactions in the floating needle treatment group, 17 (50.0%) in the duloxetine treatment group, and 7 (21.2%) in the placebo treatment group. Compared with the placebo treatment group, the incidence of adverse reaction increased in the duloxetine treatment group (χ² = 6.04, P < 0.05). Besides, it was higher in the duloxetine treatment group than in the floating needle treatment group (χ² = 14.9, P < 0.05). (3) There were 19 patients in the floating needle treatment group and 17 patients in the duloxetine treatment group involved in the follow-up study. Compared with 6 weeks after treatment, no significant difference was observed at 3 and 6 months after treatment in the score of SF-MPQ, HAMD, and HAMA in the floating needle treatment group and the duloxetine treatment group. No significant difference was observed between the two groups (P > 0.05). There were 5 patients (29.4%) who had adverse reactions in the duloxetine treatment group, and no adverse reactions were observed in the floating needle treatment group. The adverse reaction rate was significantly different between the two groups (χ² = 4.26, P < 0.05). CONCLUSIONS: Floating needle therapy and duloxetine were effective in treatment of patients with PSPD. However, floating needle therapy could relieve pain more rapidly than duloxetine, with obviously less adverse reactions.
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Terapia por Acupuntura/métodos , Analgésicos/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Manejo da Dor/métodos , Transtornos Somatoformes/terapia , Transtornos de Ansiedade , Seguimentos , Humanos , Agulhas , Dor , Medição da Dor , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
OBJECTIVES: We encountered patients with a congenital cutaneous sinus tract in the sternoclavicular joint region, which we designate as "congenital sternoclavicular sinus (CSCS)." The aim of this investigation is to enhance recognition of this subtle yet noteworthy entity and develop standardized protocols for its management. PATIENTS AND METHODS: Between 2013 and 2023, 172 patients, including 78 males and 94 females, were referred to our institution for the management of CSCS. Clinical charts were retrospectively reviewed. RESULTS: The majority of patients (60.5%) were young children below 3 years of age, with only six adult patients and a median age of 27.5 months. The left side was implicated in 157 cases (91.3%). In 146 cases (84.9%), a faint skin streak was noted above the orifice. Yet, no pharyngeal sinus tracts were detected, either through barium swallow studies or direct laryngoscopy. All skin lesions featured a diminutive orifice near the sternoclavicular joint, with the tract extending deeply into the subcutaneous tissue and terminating blindly, short of entering the joint, after a distance of 10 mm (ranging from 5 to 21 mm). Histopathological analysis revealed that the epithelial lining predominantly consisted of stratified squamous epithelium (87.8%), with ciliated columnar epithelium accounting for the remaining 12.2%. CONCLUSIONS: CSCS, though infrequent, presents with distinctive pathological and clinical features. The condition predominantly affects the left sternoclavicular joint region, with the notable "skin streak sign" aiding in diagnosis. We considered CSCS as one disease entity of branchial arch anomalies. Complete surgical excision offers a definitive cure. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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Xenotransplantation of acellular adipose matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, an innovative technique is created to bypass the immune system by covering the surface of both AAM and Arg-Gly-Asp (RGD) peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen major histocompatibility complex class 1 (MHC1) on the AAM surface. Following xenogeneic transplantation, the RBC-coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ, Adipoq, Fabp4, Fasn, and Plin1 and higher numbers of adipocytes. In addition, they exhibited decreased expression of immunological factors, including IL-6, IL-2, IFN-γ, and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.
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BACKGROUND: Adipose tissue engineering plays a key role in the reconstruction of soft-tissue defects. The acellular adipose matrix (AAM) is a promising biomaterial for the construction of engineered adipose tissue. However, AAM lacks sufficient adipoinduction potency because of the abundant loss of matrix-bound adipokines during decellularization. METHODS: An adipose-derived extracellular matrix collagen scaffold, "adipose collagen fragment" (ACF), was prepared using a novel mechanical method that provides sustained release of adipokines. Here, the authors used label-free proteomics methods to detect the protein components in AAM and ACF. In vivo, ACF was incorporated into AAM or acellular dermal matrix and implanted into nude mice to evaluate adipogenesis. Neoadipocytes, neovessels, and corresponding gene expression were evaluated. The effects of ACF on adipogenic differentiation of human adipose-derived stem cells and tube formation by human umbilical vein endothelial cells were tested in vitro. RESULTS: Proteomics analysis showed that ACF contains diverse adipogenic and angiogenic proteins. ACF can release diverse adipokines and induce highly vascularized, mature adipose tissue in AAM, and even in nonadipogenic acellular dermal matrix. Higher expression of adipogenic markers peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha and greater numbers of tubule structures were observed in ACF-treated groups in vitro. CONCLUSION: The combination of ACF and AAM could serve as a novel and promising strategy to construct mature, vascularized adipose tissue for soft-tissue reconstruction. CLINICAL RELEVANCE STATEMENT: The combined use of AAM and ACF has been proven to induce a highly vascularized, mature, engineered adipose tissue in the nude mouse model, which may serve as a promising strategy for soft-tissue reconstruction.
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Tecido Adiposo , Engenharia Tecidual , Camundongos , Animais , Humanos , Engenharia Tecidual/métodos , Camundongos Nus , Preparações de Ação Retardada/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Células Endoteliais da Veia Umbilical Humana , Alicerces Teciduais/químicaRESUMO
Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.
Assuntos
Antivirais , Infecções por Citomegalovirus , Citomegalovirus , Foscarnet , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Valganciclovir , Viremia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/etiologia , Valganciclovir/uso terapêutico , Masculino , Feminino , Viremia/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Foscarnet/uso terapêutico , Pessoa de Meia-Idade , Citomegalovirus/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem , Idoso , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/mortalidade , Resultado do Tratamento , Leucemia/terapia , Leucemia/complicações , Leucemia/mortalidadeRESUMO
The aim of this study was to explore cultural differences in causal attributions and beliefs about heritability of major depressive disorder (MDD). Face-to-face interviews with Anglo-Celtic- and Chinese-Australians community members with a family history of MDD were conducted and subjected to a rigorous qualitative analysis, using the computer software NVivo. Sixteen Anglo-Celtic-Australians and 16 Chinese-Australians were interviewed. Both groups believed that a combination of genetic and environmental factors contributed to MDD, that stress was an important cause of MDD, and that coping factors were significant moderators of the impact of stress on MDD. Both cultural groups believed that the causes of MDD affecting multiple family members included a shared family environment and a "contagion effect", in addition to genetics. Unique to the Chinese-Australian group was the beliefs that parental pressures to exceed academically contributed to MDD; this cultural group also reported beliefs that depression was due to God's will or alternatively fate, which in turn was related to attributions to feng shui and auspicious dates. This study documented key culture-specific differences in beliefs about causes and inheritance of MDD; such differences have major implications for clinician-patient communication about genetic risk associated with having a family history of MDD.