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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder affecting the upper respiratory tract. Recent studies have indicated an association between CRSwNP and mitochondrial metabolic disorder characterized by impaired metabolic pathways; however, the precise mechanisms remain unclear. This study aims to investigate the mitochondrial-related signature in individuals diagnosed with CRSwNP. Methods: Through the integration of differentially expressed genes (DEGs) with the mitochondrial gene set, differentially expressed mitochondrial-related genes (DEMRGs) were identified. Subsequently, the hub DEMRGs were selected using 4 integrated machine learning algorithms. Immune and mitochondrial characteristics were estimated based on CIBERSORT and ssGSEA algorithms. Bioinformatic findings were confirmed through RT-qPCR, immunohistochemistry, and ELISA for nasal tissues, as well as Western blotting analysis for human nasal epithelial cells (hNECs). The relationship between hub DEMRGs and disease severity was assessed using Spearman correlation analysis. Results: A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs (ALDH1L1, BCKDHB, CBR3, HMGCS2, and OXR1) were consistently downregulated in both the discovery and validation cohorts. The hub genes showed a high diagnostic performance and were positively correlated with the infiltration of M2 macrophages and resting mast cells. Experimental results confirmed that the 5 genes were downregulated at both the mRNA and protein levels within nasal polyp tissues. Finally, a significant and inverse relationship was identified between the expression levels of these genes and both the Lund-Mackay and Lund-Kennedy scores. Conclusion: Our findings systematically unraveled 5 hub markers correlated with mitochondrial metabolism and immune cell infiltration in CRSwNP, suggesting their potential to be based to design diagnostic and therapeutic strategies for the disease.
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Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.
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Macrófagos , Monócitos , Trombose Venosa , Humanos , Monócitos/imunologia , Monócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Trombose Venosa/imunologia , Trombose Venosa/metabolismo , Tromboembolia Venosa/imunologia , Tromboembolia Venosa/patologia , Tromboembolia Venosa/tratamento farmacológicoRESUMO
OBJECTIVE: Solanum nigrum L. (SNL) is a natural drugwith diverse bioactive components and multi-targeted anti-tumor effects, gaining increasing attention in clinical application. METHOD AND RESULTS: This paper reviews the studies on SNL by searching academic databases (Google Scholar, PubMed, Science Direct,and Web of Science, among others), analyzing its chemical compositions (alkaloids, saponins, polysaccharides, and polyphenols, among others), andbriefly describes the anti-tumor mechanisms of the main components. DISCUSSION: This paper discusses the shortcomings of the current research on SNL and proposes corresponding solutions, providing theoretical support for further research on its biological functions and clinical efficacy.
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Antineoplásicos Fitogênicos , Solanum nigrum , Solanum nigrum/química , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Neoplasias/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/química , Saponinas/farmacologia , Saponinas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Polifenóis/farmacologia , Polifenóis/química , Animais , Alcaloides/farmacologia , Alcaloides/químicaRESUMO
Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.
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Antibacterianos , Bandagens , Betaína , Biofilmes , Indóis , Nanofibras , Poliésteres , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Biofilmes/efeitos dos fármacos , Animais , Cicatrização/efeitos dos fármacos , Poliésteres/química , Indóis/química , Indóis/farmacologia , Betaína/química , Betaína/farmacologia , Betaína/análogos & derivados , Nanofibras/química , Polímeros/química , Óxido Nítrico/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Incrustação Biológica/prevenção & controle , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/química , Camundongos , Propriedades de Superfície , Escherichia coli/efeitos dos fármacos , Polietilenoimina/químicaRESUMO
Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.
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Neurônios GABAérgicos , Hiperalgesia , Camundongos Endogâmicos C57BL , Receptores Nicotínicos , Animais , Receptores Nicotínicos/metabolismo , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Masculino , Hiperalgesia/metabolismo , Hiperalgesia/tratamento farmacológico , Camundongos , Parte Reticular da Substância Negra/metabolismo , Parte Reticular da Substância Negra/efeitos dos fármacos , Nicotina/farmacologia , Analgésicos/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Capsaicina/farmacologia , Acetilcolina/metabolismo , Optogenética , Limiar da Dor/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD). METHODS: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups. RESULTS: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD. CONCLUSION: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism.
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Injectable hydrogel-based drug delivery systems have attracted more and more attention due to their sustained-release performance, biocompatibility, and 3D network. The present study showed whole pectin-based hydrogel as an injectable drug delivery system, which was developed from oxidized pectin (OP) and diacylhydrazine adipate-functionalized pectin (Pec-ADH) via acylhydrazone linkage. The as-prepared hydrogels were characterized by 1H NMR, FT-IR, and SEM techniques. The equilibrium swelling ratio of obtained hydrogel (i.e., sample gel 5) was up to 4306.65 % in the distilled water, which was higher than that in PBS with different pH values. Increasing the pH of the swelling media, the swelling ratio of all hydrogels decreased significantly. The results that involved the swelling properties indicated the salt- and pH-responsiveness of the as-prepared hydrogels. The drug release study presented that 5-FU can be persistently released for more than 12 h without sudden release. Moreover, the whole pectin-based hydrogel presented high cytocompatibility toward L929 cell lines, and the drug delivery system showed a high inhibitory effect on MCF-7 cell lines. All these results manifested that the acylhydrazone-derived whole pectin-based hydrogel was an excellent candidate for injectable drug delivery systems.
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BACKGROUND: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. PURPOSE: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. METHODS: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. CONCLUSIONS: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.
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Neoplasias , Tribulus , Animais , Camundongos , Simulação de Acoplamento Molecular , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2 , Transdução de Sinais , Apoptose , EsfingolipídeosRESUMO
Background: Tribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups. Results: 12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment. Conclusion: TT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.
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BACKGROUND: Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. METHODS: The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. RESULTS: The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). CONCLUSION: TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.
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Carcinoma de Células Escamosas , Timoma , Neoplasias do Timo , Humanos , Prognóstico , Timoma/patologia , Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias , Neoplasias do Timo/patologia , Estudos RetrospectivosRESUMO
Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson's disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.
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Proteínas de Neoplasias , Doença de Parkinson , Animais , Humanos , Camundongos , 1-Metil-4-fenilpiridínio , Modelos Animais de Doenças , Progressão da Doença , Neurônios Dopaminérgicos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/metabolismo , Doença de Parkinson/genética , Transdução de SinaisRESUMO
Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.
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Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Interferência de RNA , Prognóstico , Linhagem Celular TumoralRESUMO
INTRODUCTION: Studies on the level of regulatory T (Treg) cells in psoriatic arthritis (PsA) have been controversial, leading to disagreement regarding the role Treg cells play in the pathogenesis of the disease. To clarify the status of Treg cells in patients with PsA, we performed a meta-analysis to determine the levels of Treg cells and serum Treg-associated cytokines in PsA patients. METHODS: According to published data from PubMed, Web of Science, Embase, Clinical Trials.gov, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, we determined the Treg and Treg cytokine levels in patients with PsA. The effect estimates were pooled using a random-effects model. RESULTS: This meta-analysis included 12 studies. Compared to healthy controls (HCs), the proportions of Treg cells had no significant difference in patients with PsA (based on standardized means[SMD] = - 1.038, 95% confidence intervals[CI] = - 2.165 to 0.089, p = 0.071). On the basis of subgroup analysis, patients with PsA had a lower percentage of CD4+ Treg cells (SMD = - 1.501, 95% CI - 2.799 to - 0.202, p = 0.023) than OKT8+ Treg (SMD = 0.568, 95% CI - 2.127 to 3.263, p = 0.679). Besides, CD4+CD25+FoxP3+ Treg cells and CD4+CD25highCD127low Treg cells were both significantly decreased on the levels of PBMCs in patients with PsA (SMD = - 0.764, 95% CI - 1.404 to - 0.125, p = 0.019; SMD = - 5.184, 95% CI - 6.955 to - 3.412, p < 0.001). CD4+CD25+FoxP3+ Treg cells were particularly more abundant in the synovial fluid thanin peripheral blood (SMD = 3.288, 95% CI 2.127 to 4.449, p < 0.001). No significant difference was observed in the proportion of CD4+CD25+ Treg cells in peripheral blood and CD4+CD25+FoxP3+ Treg cells in CD4+ T cells (SMD = - 2.498, 95% CI - 7.720 to 2.725, p = 0.349; SMD = - 0.719, 95% CI - 2.525 to 1.086, p = 0.435). PsA patients had decreased cytokines such as transforming growth factor-ß (TGFß) (SMD = - 2.199, 95% CI - 3.650 to - 0.749, p = 0.003). CONCLUSIONS: Treg definition markers influence the scale of Treg cells in patients with PsA. Pathogenesis of PsA may be attributed to an insufficient or malfunctioning Treg population.
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Artrite Psoriásica , Linfócitos T Reguladores , Humanos , Fator de Crescimento Transformador beta , Citocinas , Fatores de Transcrição Forkhead , Fatores de Crescimento TransformadoresRESUMO
BACKGROUND: The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study. AIM: To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis. METHODS: This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes. RESULTS: A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001). CONCLUSION: A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.
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OBJECTIVES: The present study explores an extremely rare disease, thymic mucosa-associated lymphoid tissue (MALT) lymphoma, for its characteristics and prognostic factors by analyzing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From 2000 to 2018, cases with a diagnosed thymic MALT lymphoma were extracted. Clinical characteristics, treatments, and survival patterns of these cases were analyzed. RESULTS: Thymic MALT lymphoma (n = 26) accounted for 0.09% of all MALT lymphomas. With a sex ratio of 0.53 (male/female), 68% white population was affected. Most cases were diagnosed with Ann Arbor stage I (50%), yet advanced-stage did not show worse prognosis (p = 0.236). Different treatment protocols did not influence the overall prognosis (p > 0.99). The 5- and 10- year overall survival rates were 83.1% and 78.2%, respectively. Older than 70 years may be an independent risk factor for overall survival (HR = 7.166 [95% CI 1.173-43.756], p = 0.033). CONCLUSION: Thymic MALT lymphoma is a highly rare disease with a favorable prognosis. Ann Arbor staging might not be appropriate to classify severity of this disease or its treatment. Older people may have worse survival. A standardized treatment mode needs to be established, and surgery could remain as the mainstay.
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Linfoma de Zona Marginal Tipo Células B , Feminino , Humanos , Masculino , Idoso , Linfoma de Zona Marginal Tipo Células B/terapia , Doenças RarasRESUMO
Objective To investigate the clinical characteristics of 30-day unplanned reoperations after thoracic surgery. Methods We retrospectively analyzed the clinical data of patients with unplanned reoperations within 30 days after thoracic surgery in Peking Union Medical College Hospital from May 2016 to May 2021. Results The 30-day unplanned reoperations showed the incidence of 0.75%(79/10 543),the median hospital stay of 19(12,37) days,and the median hospitalization cost of 109 929.11(80 549.46,173 491.87) yuan.Twenty-two(27.85%) patients received blood transfusion and 26(32.91%) underwent intensive care.The period between May 2016 and May 2017 witnessed the most unplanned reoperations.The main causes of unplanned reoperations after thoracic surgery were bleeding(21.52%),chylothorax(17.72%),pulmonary air leakage(16.46%),atelectasis(13.92%),and gastroesophageal fistula(11.39%).Specifically,the main causes of unplanned reoperations in the patients of non-esophagus/cardia group were bleeding,pulmonary air leakage,atelectasis,and chylothorax,and those in the patients of esophagus/cardia group were gastroesophageal fistula,incision infection and poor healing,bleeding,and chylothorax.Among all the patients with unplanned reoperations,4 patients died,17 improved,and 58 recovered. Conclusions The patients who underwent unplanned reoperations after thoracic surgery had a long hospital stay and high hospitalization costs. Bleeding,chylothorax,pulmonary air leakage,atelectasis,and gastroesophageal fistula were the main reasons for the unplanned reoperations.
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Quilotórax , Atelectasia Pulmonar , Cirurgia Torácica , Humanos , Reoperação , Estudos Retrospectivos , Quilotórax/cirurgia , Hemorragia , Atelectasia Pulmonar/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
Herein, Pt@tetraphenyl-1,3-butadiene nanocrystals (Pt@TPB NCs) with high electrochemiluminescence (ECL) efficiencies as ECL emitters were developed to construct an ultrasensitive biosensing platform for the detection of microRNA-21 (miRNA-21). Interestingly, Pt@TPB NCs not only exhibited high carrier densities and electron mobilities to achieve efficient electron-hole pair recombinations for high ECL emission but also served as coreaction accelerators of endogenous coreactant-dissolved O2 with good electrocatalytic activities to produce abundant reactive oxygen species (ROS) for facilitating the interactions between TPB NCs and ROS, which further obtain intense ECL emission. Impressively, Pt@TPB NCs with dissolved O2 as coreactants displayed high ECL efficiencies (ΦECL) of 7.83, taking the ΦECL of Ru(bpy)32+/dissolved O2 ECL system as 1. Herein, Pt@TPB NCs with strong ECL signals were used as ECL emitters to combine target-induced DNA walker amplification with high conversion efficiency for the construction of an ultrasensitive ECL biosening platform which accomplished microRNA-21 detection with a low detection limit of 83.8 aM. Therefore, the developed synergy effects in Pt@TPB NCs are expected to guide the progress of highly efficient ECL emitters for sensing analysis and disease diagnosis.
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Técnicas Biossensoriais , MicroRNAs , Nanopartículas , MicroRNAs/análise , Técnicas Eletroquímicas , Medições Luminescentes , Espécies Reativas de Oxigênio , Limite de Detecção , Cristalização , Nanopartículas/química , DNA/química , AceleraçãoRESUMO
Background: Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is a rare disease. The present meta-analysis aims at accumulating current evidence to explore the clinical characteristics, treatments, and prognoses of thymic MALT lymphoma. Methods: We searched seven databases for studies published between the start date of database establishment and September 15, 2021. We included studies of patients with histological diagnoses and excluded those without data specifically on thymic MALT lymphoma. The quality was analyzed using an assessment tool. All data were tabulated. Pooled proportion was obtained using random-effects model. Statistical analysis was performed on R statistic software. Results: Overall, 52 case reports and 13 case series were eligible. The quality of case reports was inferior to that of case series in terms of selection (P<0.001). Based on the analysis of patients in the case reports, age, gender, concurrent diseases, and tumor size did not differ between limited-stage and advanced-stage cases. Surgery is the mainstay to treat thymic MALT lymphoma. The surgical approach and extent did not influence the occurrence of events. Patients at Ann Arbor stage I were prone to not receiving postoperative therapy (P=0.011), though it may not reduce the occurrence of events (P=0.637). The five-year overall survival (OS) rate and five-year progression-free survival (PFS) rate were 97.2% and 88.4%, respectively. Patients with advanced-stage disease were more likely to suffer events (P=0.009). Conclusions: Thymic MALT lymphoma is an extremely rare disease with a favorable prognosis. Currently available evidence is insufficient to draw solid judgments about treatment and prognosis. However, patients may benefit if thymectomy is chosen as the primary treatment. In some patients, lymph node sampling or dissection should be considered. In addition, if the patient is at an advanced-stage, postoperative therapy should be considered.
RESUMO
Background. Ectopic mediastinal parathyroid glands are parathyroid glands located completely below the clavicle. At present, most literature reports on ectopic mediastinal parathyroid tumors (EMPT) are case reports or small case sequences.Methods. This study conducted a retrospective analysis of ectopic mediastinal parathyroid tumors cases treated over the past 23 years, summarizing and analyzing general conditions, preoperative positioning, postoperative pathology, intraoperative conditions, and long-term follow-up results.Results. This study enrolled 28 patients. Among them, 27 patients underwent preoperative localization diagnosis using 99mTc-sestamibi scan (MIBI) in conjunction with chest computed tomography (CT), including 26 cases of the anterior superior mediastinum and 2 cases of middle mediastinum. Postoperative pathology revealed 23 cases of parathyroid adenoma, 4 cases of parathyroid hyperplasia, and 1 case of parathyroid cyst. In this study, 12 patients underwent video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches. Using Mann-Whitney U test, we discovered that VATS approach group is significantly superior in surgical time (P = 0.039) and intraoperative bleeding (P < 0.001). Within one week of surgery, 26 patients with primary hyperparathyroidism (PHPT) experienced a significant decrease in blood parathyroid hormone (PTH) (P < 0.001) and blood calcium (P < 0.001), and all achieved long-term remission.Conclusions. EMPT is most frequently performed in the anterior superior mediastinum. EMPT is predominantly parathyroid tumors, and most of them are associated with PHPT. MIBI and chest CT combination can be used for preoperative lesion localization (positive rate 96.15%). VATS can be used as a better surgical approach. PHPT patients before surgery can achieve long-term symptom relief with surgical treatment.
Assuntos
Adenoma , Neoplasias das Paratireoides , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Cálcio , Humanos , Mediastino/diagnóstico por imagem , Mediastino/patologia , Mediastino/cirurgia , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Estudos Retrospectivos , Tecnécio Tc 99m SestamibiRESUMO
ABSTRACT: Fat fixation is a key step in filling tear trough depression with inferior eyelid orbital septum fat. The ideal position for inferior eyelid fat fixation is to cross the tear trough ligament causing tear trough depression and the orbicularis retaining ligament, with the distal end fixed at the farthest end of the dissected lacuna deep down the inferior orbicularis oculi muscle. Traditional suturing is difficult in the deep narrow lacunae, but a buried guide needle can be used to suture and fix the fat in the deepest lacuna. In this study, 264 patients who underwent tear trough filling using a buried guide needle to fix the released inferior eyelid orbital septum fat from 2017 to 2020 were followed up. The preoperative and postoperative imaging findings were compared to evaluate the effectiveness of the operation and postoperative complications. The inferior eyelid bulging, loose skin, and tear trough depression significantly improved than that before the operation. None of the patients had any severe complications, such as inferior eyelid ectropion, lagophthalmos, scar hyperplasia, and diplopia, in the long term (6âmonths) postoperatively. Five patients showed mild eyelid-eyeball separation and recovered in 1âmonth. Four patients had diplopia, and 3 patients had chemosis; all recovered in 7âdays. The tear trough depression was not corrected completely in 2 patients. The operation showed satisfactory results in the improvement of tear trough depression in addition to alleviation of inferior eyelid bulging and loose inferior eyelid skin that is caused by the traditional inferior eyelid pouch removal.