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1.
Am J Ophthalmol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615831

RESUMO

PURPOSE: To evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DESIGN: Retrospective clinical cohort study. METHODS: This study included 12 unilateral RB eyes treated with IAC (RB tumour), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including foveal avascular zone (FAZ) area, the macular and peripapillary superficial vessel density (SVD) and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the three groups was conducted, while the correlations among the parameters were analyzed. RESULTS: Between the three cohorts, the foveal retinal thickness, the SVD, DVD, ChT, TCA, LA, SA and CVI were significantly lower in RB tumour compared to RB fellow and the control eyes (all P<0.01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. CONCLUSIONS: The retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. Moreover there were no measurable changes in the contralateral eyes.

2.
Br J Ophthalmol ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499321

RESUMO

AIMS: To describe the clinical features, multimodal imaging, treatments and natural course of acute spontaneous vortex vein occlusion. METHODS: Clinical data were collected on nine patients with acute vortex vein occlusion. The symptoms and signs, multimodal imaging, treatments and follow-up results were summarised. RESULTS: Six patients (66.7%) were men and three (33.3%) were women. The mean age was 47.8±15.4 years. Patients were initially misdiagnosed as having choroidal tumour (66.7%), scleritis (22.2%) and peripheral exudative haemorrhagic chorioretinopathy (11.1%). The related clinical characteristics included choroidal pseudo-tumour (100%), anterior segment injection (88.9%), acute ocular pain (77.8%), transient blurred vision (66.7%) and subsequent scleral icterus (66.7%). Six patients (66.7%) experienced a definite Valsalva manoeuvre prior to the onset. In acute phase, ultrasonography showed a low-to-medium reflective lesion without inside blood flow signal (mean thickness, 2.7±0.6 mm). Swept-source optical coherence tomography angiography (SS-OCTA) demonstrated the dilated vortex veins and ampulla with suprachoroidal haemorrhage and exudation. Indocyanine green angiography (ICGA) demonstrated choroidal circulation abnormalities in the affected quadrant. MRI showed a well-defined mass with enhancement. The main treatment was medical observation (44.5%). The choroidal pseudo-tumour spontaneously resolved with a mean course of 4.1±1.9 weeks. CONCLUSIONS: Acute vortex vein occlusion is a rare condition and initial misdiagnosis is not uncommon. It is mainly identified as an evanescent choroidal pseudo-tumour with acute pain, red eye and blurred vision. Widefield ICGA and SS-OCTA can offer valuable diagnostic clues. Medical observation may be a treatment option.

3.
Food Chem ; 447: 139013, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38507950

RESUMO

Formaldehyde is known to harm the respiratory, nervous, and digestive systems of people. In this paper, a novel dandelion-like electrocatalyst with core-shell heterostructure arrays were fast self-assembled prepared in situ using copper foam (CF) as support substrate and 2,3,6,7,10,11 hexahydroxy-triphenyl (HHTP) as ligand (Cu(OH)2@Cu3(HHTP)2/CF) by a simple two-step hydrothermal reaction. The 1D Cu(OH)2 nanorods "core" and the 2D π-conjugated conducting metal-organic frameworks (Cu3(HHTP)2cMOF) "shell" with remote delocalized electrons give the dandelion-like heterogeneous catalysts excellent electrochemical activity such as a large specific surface area, high conductivity and a fast electron transfer rate. The Cu(OH)2@Cu3(HHTP)2/CF exhibited excellent electrocatalytic performance for formaldehyde under alkaline conditions with a linear range of 0.2 µmol/L - 125 µmol/L and 125 µmol/L - 8 mmol/L, a detection limit as low as 15.9 nmol/L (S/N = 3), as well as good accuracy, consistency, and durability, and it effectively identified FA in food.


Assuntos
Cobre , Formaldeído , Humanos , Condutividade Elétrica , Transporte de Elétrons , Elétrons
4.
Int J Surg ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38537056

RESUMO

BACKGROUND: Pancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumor size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited. MATERIALS AND METHODS: A computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation. RESULTS: 9 studies including 368 patients were identified. The pooled overall incidence rate was 4% (95%CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95%CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95%CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95%CI:0-5%; I²=0.0%) for bleeding, and 4% (95%CI: 0-12%; I²=70.46%) for fever. Our subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy, but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8%-63.1%), 22.80%, and 9.5%, respectively. CONCLUSION: With the advancements in cryoablation and anti-tumor therapy, cryoablation emerges as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation.

5.
Br J Ophthalmol ; 108(4): 566-570, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36997291

RESUMO

AIMS: To describe the clinical features, imaging characteristics, histopathology, treatment and outcomes of intraocular medulloepithelioma. METHODS: Medical records of 11 patients with clinically or histopathologically confirmed medulloepithelioma were retrieved and reviewed. Clinical features, diagnostic challenges, imaging characteristics, management, histopathology and prognosis were assessed. RESULTS: The median age of the patients at initial diagnosis was 4 years, with the most common manifestations being leukocoria (five eyes), loss of vision (four eyes), ocular pain (one eye) and ophthalmic screening (one eye). The clinical signs include a grey-white ciliary body lesion, cataract or lens subluxation, secondary glaucoma and evident cysts. The ultrasound biomicroscopy (UBM) imaging most commonly displays ciliary body mass with intratumoural cysts (nine eyes). Three patients underwent surgery for cataract or glaucoma while the tumours were incidentally found. Two of the three patients managed by eye preserve treatments eventually required enucleation because of local tumour recurrence or phthisis. One patient treated with intra-arterial chemotherapy and cryotherapy had successful tumour regression and globe salvage. CONCLUSIONS: Initial misdiagnosis, delay in diagnosis and subsequent misdirected management is not uncommon in medulloepithelioma. The presence of multiple cysts in the tumour and retrolental neoplastic cyclitic membrane detected by UBM can offer certain information. Selective intra-arterial melphalan may prevent further tumour growth, but longer follow-up is necessary until treatment efficacy is fully evaluated.


Assuntos
Catarata , Cistos , Glaucoma , Doenças da Íris , Tumores Neuroectodérmicos Primitivos , Neoplasias Uveais , Humanos , Pré-Escolar , Corpo Ciliar/diagnóstico por imagem , Corpo Ciliar/patologia , Neoplasias Uveais/patologia , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/terapia , Catarata/complicações , Glaucoma/diagnóstico , Glaucoma/terapia , Glaucoma/complicações
6.
Int J Biol Sci ; 19(15): 4726-4743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781511

RESUMO

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.


Assuntos
Glicólise , Neoplasias da Próstata , Masculino , Humanos , Glicina Desidrogenase (Descarboxilante)/genética , Glicina Desidrogenase (Descarboxilante)/metabolismo , Glicólise/genética , Neoplasias da Próstata/genética
7.
BMC Musculoskelet Disord ; 24(1): 838, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875873

RESUMO

BACKGROUND: This meta-analysis compares the efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) to conventional interbody fusion in lumbar degenerative diseases (LDD). METHODS: An extensive literature search was conducted in PubMed, Web of Science, and the Cochrane Library. Research related to UBE-TLIF published up to November 2022 was reviewed. The relevant articles were selected based on inclusion and exclusion criteria, as well as an evaluation of the quality of the data extraction literature. Meta-analysis was performed using Review Manager 5.3 software. RESULTS: This meta-analysis included six high-quality case-control trials (CCTs) involving 621 subjects. The clinical outcomes assessment showed no statistical differences in complication rates, fusion rates, leg pain VAS scores, or ODI scores. After UBE-TLIF, low back pain VAS scores were significantly improved with less intraoperative blood loss and a shorter hospital stay. A longer time was required for UBE-TLIF, however. CONCLUSION: Despite the lack of sufficient high quality randomized controlled trials (RCTs) in this study, the results of this meta-analysis suggest that UBE-TLIF is more effective than open surgery in terms of length of stay, blood loss reduction during surgery, and improved low back pain after surgery. Nevertheless, the evidence will be supplemented in the future by more and better quality multicenter randomized controlled trials.


Assuntos
Dor Lombar , Fusão Vertebral , Humanos , Endoscopia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fusão Vertebral/métodos , Resultado do Tratamento
8.
Indian J Ophthalmol ; 71(8): 2959-2961, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37530264

RESUMO

Purpose: To evaluate the effect of extralesional triamcinolone acetonide (TA) injection in the treatment of small chalazion (diameter ≤ 5 mm). Methods: Prospective interventional clinal study that included patients diagnosed as chalazion of small size not responding to conservative management for at least 2 weeks. All patients were treated with extralesional TA injection (4 mg). Successful resolution of a chalazion was defined as a decrease in size to 1 mm or smaller. Results: Thirty-eight patients were included in the study. The resolution was achieved in 33 (87%) patients. Nineteen (50%) patients had complete resolution after the first injection, and 13 (34.2%) patients had complete resolution after the second injection. Chalazion near the lower punctum needed more times of injections than those elsewhere (P = 0.02). Conclusions: Extralesional TA injection is effective in the treatment of both primary and recurred small chalazia. It is a simple and cost-saving procedure and can be considered an alternative first-line treatment for small chalazion.


Assuntos
Calázio , Triancinolona Acetonida , Humanos , Calázio/diagnóstico , Calázio/tratamento farmacológico , Glucocorticoides , Estudos Prospectivos , Recidiva Local de Neoplasia
9.
Zhongguo Gu Shang ; 36(5): 465-72, 2023 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-37211941

RESUMO

OBJECTIVE: To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease. METHODS: The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T11, 5 cases of T12, 8 cases of L1, 3 cases of L2, and 1 case of L3. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up. RESULTS: Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up. CONCLUSION: Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.


Assuntos
Cifose , Parafusos Pediculares , Robótica , Fraturas da Coluna Vertebral , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Lombares/lesões , Resultado do Tratamento , Vértebras Torácicas/lesões , Fixação Interna de Fraturas
10.
Transl Cancer Res ; 12(3): 572-584, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37033345

RESUMO

Background: Sphingosine kinase 1 (SPHK1) is a key enzyme that catalyzes the phosphorylation of sphingosine. Recent studies reported SPHK1 to be associated with renal cell carcinoma (RCC) progression by inducing targeted therapy resistance. However, the expression and the clinical significance of SPHK1 on RCC in those having received targeted therapy have not been elucidated. The present study explored the expression of SPHK1 in RCC tissues from targeted therapy recipients, the correlation of SPHK1 with clinicopathological parameters, and the effect of SPHK1 on RCC patient prognosis. Methods: Differential gene expression analysis of RCC treated with and without targeted therapy was performed. The correlations of SPHK1 expression with clinical parameters of RCC were examined. Gene set enrichment analysis (GSEA) was performed to clarify the potential role of SPHK1 associated with targeted therapy resistance. The value of SPHK1 as a diagnostic marker for RCC was also evaluated. The Kaplan-Meier method was applied to analyze the correlation between SPHK1 expression and patient survival rate by using the clinical data from patients with RCC. Results: Significant overexpression of SPHK1 was detected in RCC treated with targeted therapy. SPHK1 expression was closely correlated with RCC progression-related clinicopathological parameters. Therefore, elevated SPHK1 could effectively diagnose RCC and distinguish RCC with an advanced clinical stage and a high pathological grade. SPHK1 was associated with the stemness of RCC cells via the activation of the Wnt, Hedgehog, or Notch signaling pathways in targeted drug-treated or untreated RCC. Survival analysis of a large cohort of RCC samples indicated overexpression of SPHK1 to be inversely correlated with the overall and disease-free survival of patients with RCC. Conclusions: Our study indicated that SPHK1 associated with targeted therapy resistance could serve as a potential prognostic marker and a valuable biomarker of response to angiogenic agents in RCC.

11.
Neurosci Lett ; 807: 137259, 2023 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-37075883

RESUMO

Postoperative cognitive dysfunction (POCD) is common in aged patients after major surgery and is associated with increased risk of long-term morbidity and mortality. However, the underlying mechanism remains largely unknown and the clinical management of POCD is still controversial. Stellate ganglion block (SGB) is a clinical treatment for nerve injuries and circulatory issues. Recent evidence has identified the benefits of SGB in promoting learning and memory. We thus hypothesize that SGB could be effective in improving cognitive function after surgery. In present study, we established POCD model in aged rats via partial liver resection surgery. We found that the development of POCD was associated with the activation of toll-like receptor 4/nuclear factor kapa-B (TLR4/NF-κB) signaling pathway in the microglia in dorsal hippocampus, which induced the production of pro-inflammatory mediators (TNF-α, IL-1ß, IL-6) and promoted neuroinflammation. More importantly, we showed evidence that preoperative treatment with SGB could inhibit microglial activation, suppress TLR4/NF-κB-mediated neuroinflammation and effectively attenuate cognitive decline after the surgery. Our study suggested that SGB may serve as a novel treatment to prevent POCD in elderly patients. As SGB is safe procedure widely used in clinic, our findings can be easily translated into clinical practice and benefit more patients.


Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Ratos , Animais , NF-kappa B/metabolismo , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Complicações Cognitivas Pós-Operatórias/metabolismo , Doenças Neuroinflamatórias , Receptor 4 Toll-Like/metabolismo , Gânglio Estrelado/metabolismo , Transdução de Sinais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/tratamento farmacológico , Microglia/metabolismo
13.
Heliyon ; 9(2): e13813, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36852072

RESUMO

Optic nerve invasion (ONI) is an important high-risk feature and prognostic indicator of retinoblastoma (RB). Emerging evidence has revealed that non-coding RNAs (ncRNAs) play important roles in tumor perineural invasion (PNI). Nevertheless, the regulatory role of ncRNAs in the ONI of RB is poorly understood. In the current study, whole-transcriptome sequencing was performed to assess the expression profiles of ncRNAs and mRNAs in RB tissues, with or without ONI. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we predicted the biological functions of differentially expressed (DE) mRNAs. We then constructed competing endogenous RNA (ceRNA) regulatory networks based on bioinformatics analysis. The hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1 pathway was selected and validated by real-time qPCR, western blotting, and dual luciferase reporter assays. Moreover, we demonstrated that NOTCH1 promotes the malignant progression of RB. Taken together, our results provide novel insights into the mechanism underlying optic nerve invasion in RB.

14.
Int J Ophthalmol ; 16(2): 233-237, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816213

RESUMO

AIM: To characterize spectral-domain optical coherence tomography (SD-OCT) features of chorioretinal folds in orbital mass imaged using enhanced depth imaging (EDI). METHODS: Prospective observational case-control study was conducted in 20 eyes of 20 patients, the uninvolved eye served as a control. All the patients underwent clinical fundus photography, computed tomography, EDI SD-OCT imaging before and after surgery. Two patients with cavernous hemangiomas underwent intratumoral injection of bleomycin A5; the remaining patients underwent tumor excision. Patients were followed 1 to 14mo following surgery (average follow up, 5.8mo). RESULTS: Visual acuity prior to surgery ranged from 20/20 to 20/200. Following surgery, 5 patients' visual acuity remained unchanged while the remaining 15 patients had a mean letter improvement of 10 (range 4 to 26 letters). Photoreceptor inner/outer segment defects were found in 10 of 15 patients prior to surgery. Following surgical excision, photoreceptor inner/outer segment defects fully resolved in 8 of these 10 patients. CONCLUSION: Persistence of photoreceptor inner/outer segment defects caused by compression of the globe by an orbital mass can be associated with reduced visual prognosis. Our findings suggest that photoreceptor inner/outer segment defects on EDI SD-OCT could be an indicator for immediate surgical excision of an orbital mass causing choroidal compression.

15.
Asian J Androl ; 25(4): 474-483, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36537377

RESUMO

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood-testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.


Assuntos
Proteínas Quinases Ativadas por AMP , Exossomos , Camundongos , Masculino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Exossomos/metabolismo , Células Intersticiais do Testículo/metabolismo , Qualidade de Vida , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Autofagia/fisiologia , Testosterona/metabolismo , Mamíferos
16.
Eye (Lond) ; 37(8): 1571-1576, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35902746

RESUMO

PURPOSE: To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression. METHODS: Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups. RESULTS: After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively. CONCLUSION: Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.


Assuntos
Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/cirurgia , Tomografia de Coerência Óptica/métodos , Células Ganglionares da Retina , Fibras Nervosas , Descompressão
17.
Int J Surg ; 109(12): 4309-4321, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38259002

RESUMO

BACKGROUND: Pancreatic cancer frequently involves the surrounding major arteries, preventing surgeons from making a radical excision. Neoadjuvant therapy (NAT) can lessen the size of local tumors and eliminate potential micrommetastases. However, systematic and evidence-based recommendations for the treatment of arterial resection (AR) after NAT in pancreatic cancer are scarce. METHOD: A computerized search of the Medline, Embase, Cochrane Library databases, and Clinicaltrials was performed to identify studies reporting the outcomes of patients who underwent pancreatectomy with AR and NAT for pancreatic cancer. Studies that reported perioperative and/or long-term results after pancreatectomy with AR and NAT were eligible for inclusion. The quality of the evidence was assessed with Newcastle-Ottawa Quality Assessment Form of bias tool. Data were pooled and analyzed by Stata 14.0 software. RESULT: Nine studies with an overall sample size of 215 met our eligibility criteria and were included in the meta-analysis. All studies were retrospective studies, and the methodological quality was moderate. The pooled morbidity and mortality rates were 51% (95% CI: 41-61%; I²= 0.0%) and 2% (95% CI: 0-0.08; I²=33.3%), respectively. Meta-analysis showed that the overall R0 resection rate was 79% (CI: 70-86%, I²=15.5%). Comparative data on R0 rates of patients who underwent pancreatectomy with and without NAT showed a significant difference in favor of the former group with moderate statistical heterogeneity (Relative risk=1.21; 95% CI: 0.776-1.915; I²=48.0%). The median 1-, 2-, 3-, and 5-year survival rates of patients who had AR were 92.3% (range: 72.7-100%), 64.8% (range: 25-78.8%), 51.6% (range: 16.7-63.6%), and 14% (range: 0-41.1%), respectively. Data on median progression-free survival ranged from 5.25 to 36.3 months, and the median overall survival ranged from 17 to 44.9 months. CONCLUSIONS: Pancreatectomy with major AR following NAT has the potential to enhance the survival rate of patients with unresectable pancreatic cancer involving the arteries by achieving R0 resection, despite a significant risk of postoperative complications. However, to validate the feasibility and effectiveness of this procedure, prospective controlled studies are necessary to address limitations arising from small sample sizes and potential biases inherent in retrospective studies.


Assuntos
Segunda Neoplasia Primária , Neoplasias Pancreáticas , Humanos , Pancreatectomia/efeitos adversos , Terapia Neoadjuvante , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Artérias
18.
Front Immunol ; 13: 946209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569837

RESUMO

Background: Plasma cells as an important component of immune microenvironment plays a crucial role in immune escape and are closely related to immune therapy response. However, its role for prostate cancer is rarely understood. In this study, we intend to investigate the value of a new plasma cell molecular subtype for predicting the biochemical recurrence, immune escape and immunotherapy response in prostate cancer. Methods: Gene expression and clinicopathological data were collected from 481 prostate cancer patients in the Cancer Genome Atlas. Then, the immune characteristics of the patients were analyzed based on plasma cell infiltration fractions. The unsupervised clustering based machine learning algorithm was used to identify the molecular subtypes of the plasma cell. And the characteristic genes of plasma cell subtypes were screened out by three types of machine learning models to establish an artificial neural network for predicting plasma cell subtypes. Finally, the prediction artificial neural network of plasma cell infiltration subtypes was validated in an independent cohort of 449 prostate cancer patients from the Gene Expression Omnibus. Results: The plasma cell fraction in prostate cancer was significantly decreased in tumors with high T stage, high Gleason score and lymph node metastasis. In addition, low plasma cell fraction patients had a higher risk of biochemical recurrence. Based on the differential genes of plasma cells, plasma cell infiltration status of PCa patients were divided into two independent molecular subtypes(subtype 1 and subtype 2). Subtype 1 tends to be immunosuppressive plasma cells infiltrating to the PCa region, with a higher likelihood of biochemical recurrence, more active immune microenvironment, and stronger immune escape potential, leading to a poor response to immunotherapy. Subsequently, 10 characteristic genes of plasma cell subtype were screened out by three machine learning algorithms. Finally, an artificial neural network was constructed by those 10 genes to predict the plasma cell subtype of new patients. This artificial neural network was validated in an independent validation set, and the similar results were gained. Conclusions: Plasma cell infiltration subtypes could provide a potent prognostic predictor for prostate cancer and be an option for potential responders to prostate cancer immunotherapy.


Assuntos
Inteligência Artificial , Neoplasias da Próstata , Masculino , Humanos , Plasmócitos , Algoritmos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Imunoterapia , Microambiente Tumoral/genética
19.
Front Oncol ; 12: 879394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719929

RESUMO

Purpose: To establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population. Patients and Methods: A total of 295 consecutive cases treated at the Eye & ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC (area under the Receiver Operating Characteristic, ROC curve), and Brier score were calculated and compared. Results: Based on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts. Conclusion: Our nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions.

20.
Front Pharmacol ; 13: 843110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250590

RESUMO

Objective: To summarize the current therapeutic status using chemotherapeutic agent docetaxel and endocrine therapeutic agents (ARAT, abiraterone, orteronel or enzalutamide) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including sequential therapy and combined therapy, to promote the consensus on the optimal regimen for achieving superior treatment efficacy. Methods: Through literature search in PubMed, articles with the following relevant keywords were collected and anlyzed: CRPC, abiraterone, orteronel and enzalutamide, median survival, overall survival, prostate specific antigen (PSA), PSA response rate and median radiologic progression-free survival. Results: Fifty-eight articles were obtained and analyzed in this review. These articles included androgen axis-targeting agents after docetaxel, docetaxel after androgen axis-targeting agents, Triple sequential and combination therapy, covering four current drugs for mCRPC treatment: docetaxel, abiraterone, orteronel, and enzalutamide. It was found that there may be some cross-resistance between androgen axis-targeting agents, which will reduce the efficacy of subsequent drug treatment. Although neither of the studies of using combination therapy showed serious drug toxicity, the efficacy of sequential therapy was not as good as expected. Most adverse reactions after treatment were reported to be level 1-2. Conclusion: Based on the results of the current studies, abiraterone followed by enzalutamide treatment is the best sequential treatment for most docetaxel-naïve patients. This treatment achieves not only good OS, but also PFS and PSA response rates. In addition, for patients who have previously failed docetaxel treatment, enzalutamide is the best choice as the subsequent treatment.

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