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1.
Opt Express ; 32(6): 9699-9709, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571198

RESUMO

In order to enhance the performance of a continuous-wave photocathode electron gun at Peking University, and to achieve electron beams with higher current and brightness, a multifunctional drive laser system named PULSE (Peking University drive Laser System for high-brightness Electron source) has been developed. This innovative system is capable of delivering an average output power of 120 W infrared laser pulse at 81.25 MHz, as well as approximately 13.8 W of green power with reliable stability. The utilization of two stages of photonic crystal fibers plays a crucial role in achieving this output. Additionally, the incorporation of two acousto-optic modulators enables the selection of macro-pulses with varying repetition frequencies and duty cycles, which is essential for effective electron beam diagnosis. Furthermore, the system employs a series of birefringent crystals for temporal pulse shaping, allowing for stacking Gaussian pulses into multiple types of distribution. Overall, the optical schematic and operating performance of PULSE are detailed in this paper.

2.
J Nanobiotechnology ; 20(1): 90, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189896

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous cancer required combination therapy, such as photothermal therapy and chemotherapy. In recent years, cancer immunotherapies are rapidly evolving and are some of the most promising avenues to approach malignancies. Thus, the combination of the traditional therapies and immunotherapy in one platform may improve the efficacy for HCC treatment. RESULTS: In this work, we have prepared a black phosphorus (BP)-Au-thiosugar nanosheets (BATNS), in which Au-thiosugar coating and functionalization improved the stability of both black phosphorus nanosheets (BPNS) and gold ions in different simulated physiological environments. The compression of the BATNS band gap can convert more photon energy to heat generation compared with BPNS, resulting in higher photothermal conversion efficiency. The in vitro and in vivo results also revealed a stronger reduction on the hepatocellular carcinoma of mice and prolonged survival of disease models compared with BPNS. More importantly, BATNS showed an additional immune effect by increasing local NK cell infiltration but not T cell on the liver cancer treatment, and this immune effect was caused by the thermal effect of BATNS photothermal treatment. CONCLUSIONS: The novel BATNS could improve the stability of BPNS and simultaneously combine the cancer thermotherapy and immunotherapy leaded by local NK cell infiltration, resulting in a better therapeutic efficacy on hepatocellular carcinoma. This work also provided a new path to design BP-based materials for biomedical applications.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Tioaçúcares , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Humanos , Células Matadoras Naturais , Neoplasias Hepáticas/terapia , Fósforo/farmacologia
3.
Opt Express ; 29(18): 29550-29556, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34615063

RESUMO

The photocathode drive laser system in the Institute of High Energy Physics (IHEP) has been upgraded. An all-fiber drive laser system has been developed using photonic crystal fibers and photonic crystal rods as the main gain medium. This system has been operated stably. The output infrared (IR) power reaches 116.2 W. The pulse width and maximum output power of the green laser generated by the second harmonic generation (SHG) are less than 2 ps and about 39.4 W, respectively. The SHG efficiency exceeds 60%. This paper introduces the development of the drive laser system and reports the measurement results of the performance test.

4.
BMC Ophthalmol ; 21(1): 19, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413210

RESUMO

BACKGROUND: The use of capsular tension ring (CTR) implantation to treat cataract patients with weak zonules is still controversial. The aim of this study was to examine the effects of CTR implantation on capsular stability after phacoemulsification in patients with weak zonules, especially patients who have undergone pars plana vitrectomy (PPV) or those who suffer from severe myopia. METHODS: A total of 42 patients who underwent phacoemulsification and received an intraocular lens (IOL) were randomized to undergo CTR implantation or not. The control and CTR groups were compared in terms of uncorrected distant visual acuity (UDVA), best corrected distant visual acuity (BCDVA), refractive prediction error, the area of anterior capsulorhexis, and IOL inclination angle. Follow-up visits were conducted postoperatively at 1 day, 1 week, 1 month and 3 months. Subgroup analyses were performed based on PPV and severe myopia. RESULTS: Surgery significantly improved UDVA and BCDVA to similar extents in CTR and control patients, and refraction prediction error was similar between the two groups at all follow-up times. At 3 months after surgery, the area of anterior capsulorhexis was significantly larger in CTR patients than in controls (p = 0.0199). These differences were also significant between the subgroups of patients with severe myopia. Vertical IOL inclination was less within CTR groups at 3 months after surgery, especially in patients with severe myopia (p = 0.0286). At 1 week postoperatively, the proportion of individuals whose posterior lens capsule that had completely adhered to the posterior IOL surface was significantly higher among CTR patients (p = 0.023). No serious surgical complications were observed. CONCLUSION: CTR implantation can benefit cataract patients with weak zonules by maintaining the shape of the capsular bag, reducing capsule shrinkage and stabilizing IOL inclination. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-INR-17011217 , date of registration April 22, 2017, prospectively registered.


Assuntos
Extração de Catarata , Catarata , Cápsula do Cristalino , Lentes Intraoculares , Facoemulsificação , Catarata/complicações , Humanos , Cápsula do Cristalino/cirurgia , Implante de Lente Intraocular
5.
Molecules ; 25(21)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33139647

RESUMO

Neglected parasitic diseases remain a major public health issue worldwide, especially in tropical and subtropical areas. Human parasite diversity is very large, ranging from protozoa to worms. In most cases, more effective and new drugs are urgently needed. Previous studies indicated that the gold(I) drug auranofin (Ridaura®) is effective against several parasites. Among new gold(I) complexes, the phosphole-containing gold(I) complex {1-phenyl-2,5-di(2-pyridyl)phosphole}AuCl (abbreviated as GoPI) is an irreversible inhibitor of both purified human glutathione and thioredoxin reductases. GoPI-sugar is a novel 1-thio-ß-d-glucopyranose 2,3,4,6-tetraacetato-S-derivative that is a chimera of the structures of GoPI and auranofin, designed to improve stability and bioavailability of GoPI. These metal-ligand complexes are of particular interest because of their combined abilities to irreversibly target the essential dithiol/selenol catalytic pair of selenium-dependent thioredoxin reductase activity, and to kill cells from breast and brain tumors. In this work, screening of various parasites-protozoans, trematodes, and nematodes-was undertaken to determine the in vitro killing activity of GoPI-sugar compared to auranofin. GoPI-sugar was found to efficiently kill intramacrophagic Leishmania donovani amastigotes and adult filarial and trematode worms.


Assuntos
Anti-Helmínticos , Antineoplásicos , Antiprotozoários , Auranofina , Complexos de Coordenação , Ouro , Helmintíase/tratamento farmacológico , Neoplasias/tratamento farmacológico , Infecções por Protozoários/tratamento farmacológico , Animais , Anti-Helmínticos/química , Anti-Helmínticos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiprotozoários/química , Antiprotozoários/farmacologia , Auranofina/química , Auranofina/farmacologia , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Avaliação de Medicamentos , Ouro/química , Ouro/farmacologia , Helmintíase/metabolismo , Helmintíase/patologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Infecções por Protozoários/metabolismo , Infecções por Protozoários/patologia
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 18-23, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-31950784

RESUMO

OBJECTIVE: To study the expression and secretion of alternative complement pathway regulator complement factor H (CFH) in spontaneously produced or induced human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: RPE cells were acquired by spontaneous differentiation from hESC (sdRPE), a source of hESC-RPE, according to the method used in clinical trials. RPE cells were also acquired under the induction of growth factors and small molecules for 14 d (iRPE). Acquired cells were kept culturing for 3 month for maturation. All differentiated cells(P3)were cultivated for 4-5 weeks prior to characterization with qRT-PCR and immunofluorescence. Secretion levels of CFH were investigated by ELISA. ARPE-19 cell line was served as control. RESULTS: Both sdRPE and iRPE showed high similarity in cell morphology and the pattern of specific gene expression with human RPE. The relative CFH mRNA expression levels of both sdRPE and iRPE were significantly higher than that of ARPE-19 ( P<0.05). The CFH secretion levels of sdRPE in the 24 h-, 48 h- and 72 h-culture medium were higher than those of iRPE ( P=0.000 2); and this CFH secretion levels of both sdRPE and iRPE were higher than that of the ARPE-19 cell line ( P<0.000 1). CONCLUSION: Both sdRPE and iRPE derived by different differentiation methods expressed and secreted CFH, suggesting that hESC-RPE may have certain ability to regulate the alternative complement pathway.


Assuntos
Fator H do Complemento , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Embrionárias Humanas , Epitélio Pigmentado da Retina , Linhagem Celular , Fator H do Complemento/genética , Via Alternativa do Complemento/genética , Humanos , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo
7.
Retina ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38564760
8.
Org Biomol Chem ; 16(15): 2647-2665, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29542786

RESUMO

Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully 13C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation. Furthermore, with the help of UHPLC-MS/MS, two of the drug metabolites have been identified from urine of drug-treated mice.


Assuntos
Antimaláricos/síntese química , Vitamina K 3/análogos & derivados , Vitamina K 3/síntese química , Animais , Antimaláricos/metabolismo , Antimaláricos/farmacologia , Isótopos de Carbono , Resistência a Múltiplos Medicamentos , Humanos , Marcação por Isótopo , Camundongos , Oxirredução , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Vitamina K 3/metabolismo , Vitamina K 3/farmacologia
10.
Ther Clin Risk Manag ; 20: 249-259, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736989

RESUMO

Purpose: The purpose of this study is to preliminarily assess the change in perioperative systemic inflammatory markers and clinical outcomes between open TLIF and BE-TLIF procedures. Patients and Methods: In total, 38 patients who underwent single-level lumbar fusion surgery (L4-5 or L5-S1) were retrospectively reviewed. 19 patients were treated by the BE-TLIF technique, while the other patients were managed using open TLIF. The perioperative serum C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) of the two groups were compared to determine if there was a statistical difference. Meanwhile, clinical evaluations were conducted to assess various factors including operative duration, estimated blood loss (EBL), drainage catheter stay, length of hospitalization, visual analogue scale (VAS), and Oswestry disability index (ODI) scores. Results: The perioperative analysis revealed that BE-TLIF cases experienced a longer operative duration than open TLIF cases (open TLIF: 138.63 ± 31.59 min, BE-TLIF: 204.58 ± 49.37 min, p < 0.001). Meanwhile, the EBL showed an increased trend in the BE-TLIF group (260.7 ± 211.9 mL) in comparison with the open TLIF group (200.9 ± 211.9 mL) (p =0.485). In terms of systemic inflammatory markers, the mean postoperative CRP, NLR, LMR, and PLR were lower in the BE-TLIF group than in the open TLIF group, although these differences were not statistically significant (p > 0.05). The VAS and ODI scores in both groups were significantly improved after surgery (p < 0.05). Conclusion: There was no significant difference found between BE-TLIF and open TLIF in terms of systemic inflammatory markers, and clinical outcomes. Overall, BE-TLIF can be considered a viable choice for lumbar canal decompression and interbody fusion for less invasion. It is worth noting that BE-TLIF does have a longer operation time, indicating that there is still potential for further improvement in this technique.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38512709

RESUMO

Background: Osteosarcoma (OS) is undeniably a formidable bone malignancy characterized by a scarcity of effective treatment options. Reprogramming of amino acid (AA) metabolism has been associated with OS development. The present study was designed to identify metabolism-associated genes (MAGs) that are differentially expressed in OS and to construct a MAG-based prognostic risk signature for this disease. Methods: Expression profiles and clinicopathological data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena databases. A set of AA MAGs was obtained from the MSigDB database. Differentially expressed genes (DEGs) in GEO dataset were identified using "limma." Prognostic MAGs from UCSC Xena database were determined through univariate Cox regression and used in the prognostic signature development. This signature was validated using another dataset from GEO database. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, single sample gene set enrichment analysis, and GDSC2 analyses were performed to explore the biological functions of the MAGs. A MAG-based nomogram was established to predict 1-, 3-, and 5-year survival. Real-time quantitative polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of MAGs in primary OS and paired adjacent normal tissues. Results: A total of 790 DEGs and 62 prognostic MAGs were identified. A MAG-based signature was constructed based on four MAGs: PIPOX, PSMC2, SMOX, and PSAT1. The prognostic value of this signature was successfully validated, with areas under the receiver operating characteristic curves for 1-, 3-, and 5-year survival of 0.714, 0.719, and 0.715, respectively. This MAG-based signature was correlated with the infiltration of CD56dim natural killer cells and resistance to several antiangiogenic agents. The nomogram was accurate in predictions, with a C-index of 0.77. The expression of MAGs verified by experiment was consistent with the trends observed in GEO database. Conclusion: Four AA MAGs were prognostic of survival in OS patients. This MAG-based signature has the potential to offer valuable insights into the development of treatments for OS.

12.
ACS Infect Dis ; 10(5): 1808-1838, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38606978

RESUMO

Chagas disease, or American trypanosomiasis, is a neglected tropical disease which is a top priority target of the World Health Organization. The disease, endemic mainly in Latin America, is caused by the protozoan Trypanosoma cruzi and has spread around the globe due to human migration. There are multiple transmission routes, including vectorial, congenital, oral, and iatrogenic. Less than 1% of patients have access to treatment, relying on two old redox-active drugs that show poor pharmacokinetics and severe adverse effects. Hence, the priorities for the next steps of R&D include (i) the discovery of novel drugs/chemical classes, (ii) filling the pipeline with drug candidates that have new mechanisms of action, and (iii) the pressing need for more research and access to new chemical entities. In the present work, we first identified a hit (4a) with a potent anti-T. cruzi activity from a library of 3-benzylmenadiones. We then designed a synthetic strategy to build a library of 49 3-(4-monoamino)benzylmenadione derivatives via reductive amination to obtain diazacyclic benz(o)ylmenadiones. Among them, we identified by high content imaging an anti-amastigote "early lead" 11b (henceforth called cruzidione) revealing optimized pharmacokinetic properties and enhanced specificity. Studies in a yeast model revealed that a cruzidione metabolite, the 3-benzoylmenadione (cruzidione oxide), enters redox cycling with the NADH-dehydrogenase, generating reactive oxygen species, as hypothesized for the early hit (4a).


Assuntos
Doença de Chagas , Oxirredução , Tripanossomicidas , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Animais , Tripanossomicidas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/síntese química , Humanos , Camundongos
13.
Cancer Med ; 12(12): 13111-13122, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37132269

RESUMO

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. METHODS: In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C-index, calibration curve, time-dependent ROC curve, and DCA curve. Kaplan-Meier survival curves were also generated to illustrate the differences in cancer-specific survival (CSS) between the groups. RESULTS: The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer-specific survival in the training cohort. Both the C-index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high- and low-risk groups were observed. CONCLUSIONS: Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Nomogramas , Cárdia , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia
14.
Thorac Cancer ; 14(22): 2127-2138, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37337933

RESUMO

BACKGROUND: Although radiotherapy has improved local control in esophageal squamous cell carcinoma (ESCC), a considerable number of patients still experience relapse due to resistance. In this study, we aimed to evaluate the effects of cetuximab on radiosensitivity in two ESCC cell lines (ECA109 and TE-13) and to investigate their underlying mechanisms. METHODS: Cells were pretreated with or without cetuximab before irradiation. The MTT assay and clonogenic survival assay were performed to evaluate cell viability and radiosensitivity. Flow cytometry was performed to analyze cell cycle distribution and apoptosis. The γH2AX foci were counted to determine cellular DNA-repairing capacity via immunofluorescence assay. The phosphorylation of key molecules involved in the epidermal growth factor receptor (EGFR) signaling pathway and DNA double-strand break (DSB) repair were measured by western blot. RESULTS: Cetuximab alone was not sufficient to suppress cell viability, but significantly enhanced radiation-induced inhibition of clonogenic survival in ECA109 and TE-13. The radiation sensitivity enhancement ratio (SER) was 1.341 and 1.237 for ECA109 and TE-13, respectively. ESCC cells treated with cetuximab were arrested at the G2/M phase in response to radiation. No significant increase in apoptotic rate was observed in irradiated cells that were treated with cetuximab. The average number of γH2AX foci increased in the combination group (cetuximab and radiation). Cetuximab suppressed phosphorylation of EGFR and downstream ERK, but had no significant effect on AKT. CONCLUSIONS: These results indicate the potential for use of cetuximab as an effective radiosensitizer in ESCC. Cetuximab promotes G2/M cycle arrest and reduces DSB repair, as well as inhibiting EGFR and downstream ERK pathways in ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Cetuximab/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Recidiva Local de Neoplasia , Receptores ErbB/genética , Tolerância a Radiação , Reparo do DNA , Apoptose , DNA , Linhagem Celular Tumoral
15.
Mater Horiz ; 10(12): 5474-5483, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-37703055

RESUMO

Chronic diabetic wounds persistently face the threat of evolving into diabetic foot ulcers owing to severe hypoxia, high levels of reactive oxygen species (ROS), and a complex inflammatory microenvironment. To concurrently surmount these obstacles, we developed an all-round therapeutic strategy based on nanozymes that simultaneously scavenge ROS, generate O2 and regulate the immune system. First, we designed a dynamic covalent bond hybrid of a metal-organic coordination polymer as a synthesis template, obtaining high-density platinum nanoparticle assemblies (PNAs). This compact assembly of platinum nanoparticles not only effectively simulates antioxidant enzymes (CAT, POD) but also, under ultrasound (US), enhances electron polarization through the surface plasmon resonance effect, endowing it with the ability to induce GSH generation by effectively replicating the enzyme function of glutathione reductase (GR). PNAs, by mimicking the activity of CAT and POD, effectively catalyze hydrogen peroxide, alleviate hypoxia, and effectively generate GSH under ultrasound, further enhancing ROS scavenging. Notably, PNAs can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. It was confirmed that PNAs can enhance cell proliferation and migration, promote neoangiogenesis IN VITRO, and accelerate the healing of infected diabetic wounds IN VIVO. We believe that an all-round therapeutic method based on PNA nanozymes could be a promising strategy for sustained diabetic wound healing.


Assuntos
Pé Diabético , Nanopartículas Metálicas , Ácidos Nucleicos Peptídicos , Humanos , Hidrogéis , Nanopartículas Metálicas/uso terapêutico , Platina , Espécies Reativas de Oxigênio , Hipóxia
16.
Nat Commun ; 14(1): 1343, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906577

RESUMO

Cuprate high-Tc superconductors are known for their intertwined interactions and the coexistence of competing orders. Uncovering experimental signatures of these interactions is often the first step in understanding their complex relations. A typical spectroscopic signature of the interaction between a discrete mode and a continuum of excitations is the Fano resonance/interference, characterized by the asymmetric light-scattering amplitude of the discrete mode as a function of the electromagnetic driving frequency. In this study, we report a new type of Fano resonance manifested by the nonlinear terahertz response of cuprate high-Tc superconductors, where we resolve both the amplitude and phase signatures of the Fano resonance. Our extensive hole-doping and magnetic field dependent investigation suggests that the Fano resonance may arise from an interplay between the superconducting fluctuations and the charge density wave fluctuations, prompting future studies to look more closely into their dynamical interactions.

17.
Exp Biol Med (Maywood) ; 247(2): 77-86, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775843

RESUMO

Age-related macular degeneration is the leading cause of blindness in the elderly. The Y402H polymorphism in complement factor H promotes disease-like pathogenesis, and a Cfh+/- murine model can replicate this phenotype, but only after two years. We reasoned that by combining CFH deficiency with cigarette smoke exposure, we might be able to accelerate disease progression to facilitate preclinical research in this disease. Wild-type and Cfh+/- mice were exposed to nose-only cigarette smoke for three months. Retinal tissue morphology and visual function were evaluated by optical coherence tomography, fundus photography and autofluorescence, and electroretinogram. Retinal pigment epithelial cell phenotype and ultrastructure were evaluated by immunofluorescence staining and transmission electron microscopy. Cfh+/- smoking mice showed a dome-like protruding lesion at the ellipsoid zone (drusen-like deposition), many retinal hyper-autofluorescence spots, and a marked decrease in A- and B-wave amplitudes. Compared with non-smoking mice, wild-type and Cfh+/- smoking mice showed sub-retinal pigment epithelium complement protein 3 deposition, activation of microglia, metabolic waste accumulation, and impairment of tight junctions. Microglia cells migrated into the photoreceptor outer segment layer in Cfh+/- smoking mice showed increased activation. Our results suggest that exposing Cfh+/- mice to smoking leads to earlier onset of age-related macular degeneration than in other animal models, which may facilitate preclinical research into the pathophysiology and treatment of this disease.


Assuntos
Fator H do Complemento/deficiência , Doenças da Deficiência Hereditária de Complemento/metabolismo , Nefropatias/metabolismo , Degeneração Macular/metabolismo , Fumar/metabolismo , Animais , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Modelos Animais de Doenças , Doenças da Deficiência Hereditária de Complemento/genética , Nefropatias/genética , Degeneração Macular/etiologia , Degeneração Macular/genética , Camundongos , Camundongos Knockout , Fumar/efeitos adversos , Fumar/genética
18.
Front Surg ; 9: 956256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386541

RESUMO

Background: We aimed to construct nomograms based on clinicopathological features and routine preoperative hematological indices to predict cancer-specific survival (CSS) and disease-free survival (DFS) in patients with stage II/III gastric adenocarcinoma (GA) after radical resection. Methods: We retrospectively analyzed 468 patients with stage II/III GA after curative gastrectomy between 2012 and 2018; 70% of the patients were randomly assigned to the training set (n = 327) and the rest were assigned to the validation set (n = 141). The nomogram was constructed from independent predictors derived from the Cox regression in the training set. Using the consistency index, the calibration and the time-dependent receiver operating characteristic curves were used to evaluate the accuracy of the nomogram. Decision curve analysis was used to assess the value of the model in clinical applications. Patients were further divided into low- and high-risk groups based on the nomogram risk score. Results: Multivariate Cox model identified depth of invasion, lymph node invasion, tumor differentiation, adjuvant chemotherapy, CA724, and platelet-albumin ratio as covariates associated with CSS and DFS. CA199 is a risk factor unique to CSS. The nomogram constructed using the results of the multivariate analysis showed high accuracy with a consistency index of 0.771 (CSS) and 0.771 (DFS). Moreover, the area under the curve values for the 3-and 5-year CSS were 0.868 and 0.918, and the corresponding values for DFS were 0.872 and 0.919, respectively. The nomogram had a greater clinical benefit than the TNM staging system. High-risk patients based on the nomogram had a worse prognosis than low-risk patients. Conclusion: The prognostic nomogram for patients with stage II/III GA after radical gastrectomy established in this study has a good predictive ability, which is helpful for doctors to accurately evaluate the prognosis of patients to make more reasonable treatment plans.

19.
Ann Transl Med ; 10(3): 156, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284555

RESUMO

Giant cell tumor of bone (GCTB) is a rare borderline tumor which can develop lung metastasis. Guidelines for patients with multiple pulmonary metastases recommend systemic therapies, such as denosumab and interferons (IFNs). However, when both of these treatment approaches fail, no satisfactory options are available. Thus, additional treatments for GCTB after failure of standard treatment would be beneficial. Here we present a patient with GCTB and multiple pulmonary metastases who was treated with stereotactic body radiotherapy (SBRT) after failure of surgery, denosumab, and bisphosphonates (BPs). This is the first well-documented report of a patient with metastatic GCTB who received lung SBRT after the failure of systemic therapy and achieved a favorable response. Some of the patient's pulmonary metastases were treated using SBRT (44 Gy/4 F). The long diameters of the irradiated nodules decreased 58.2% from baseline in the 30 months after SBRT. Moreover, the peritumoral volume of another nodule also shrank by 29.1% after receiving a low-scatter dose of 7.6 Gy/4 F, which was too small to have induced tumor regression. No obvious adverse events were observed during SBRT or in the follow-up period. Our case provides clinical evidence that SBRT may be a safe and effective method to treat metastatic GCTB and can produce a low-dose radiation-induced abscopal response, suggesting that immune responses can contribute to GCTB regression. In addition, we reviewed publications regarding treatment recommendations, the prospects for SBRT application, and possible effects of abscopal responses on GCTB.

20.
Transl Cancer Res ; 11(9): 3156-3174, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36237232

RESUMO

Background: Osteosarcoma is a severe malignancy with relatively low morbidity and significant variation in patient outcomes. Thus the development of predictive models could help clinicians make better-individualized decisions. The present study established a nomogram to predict postoperative survival of osteosarcoma patients using the large population-based Surveillance, Epidemiology, and End Results (SEER) database and validated it with single-center data from an Asian/Chinese population. Methods: Data from osteosarcoma patients who underwent surgery from 2000 to 2016 in the SEER database were obtained and were randomly divided into a training set (n=1,057) and an internal validation set (n=1,057). Data from osteosarcoma patients who underwent surgery in our hospital from 2013 to 2016 were collected as an external validation set (n=65). Univariate and multivariate Cox proportional hazard models were used in the training set to screen for prognostic factors and a nomogram was established to individually predict 1-, 3- and 5-year cancer-specific survival (CSS) and overall survival (OS). The discrimination and calibration ability of the nomogram were evaluated using the Harrell concordance index (C-index), calibration curves and area under the curve (AUC). The clinical utility was evaluated using decision curve analysis (DCA). Results: Predictive nomograms were generated using characteristics including age, pathological subtype, the American Joint Committee on Cancer (AJCC) group-N, AJCC-M, tumor size, and tumor extension for CSS and OS. The C-indexes for the CSS training set, the internal validation set, and the external validation set were 0.731, 0.713, and 0.721, respectively. The C-indexes of OS C-indices were 0.734, 0.706, and 0.719, respectively. The calibration curve suggested that the nomograms were accurate in their predictions and that DCA showed broad clinical benefits. Moreover, the present nomograms exhibited high accuracy (for CSS: AUC =0.871, 0.772, and 0.759 of 1-, 3-, and 5-year; for OS: AUC =0.869, 0.774, and 0.765 of 1-, 3-, and 5-year) versus AJCC-Stage (for CSS: AUC =0.744, 0.670, and 0.671 of 1-, 3-, and 5-year; for OS: AUC =0.721, 0.665, and 0.662 of 1-, 3-, and 5-year). Conclusions: This study developed and validated a prognostic nomogram integrating clinicopathological characteristics for osteosarcoma patients who underwent surgery. This nomogram can provide individual risk assessment for survival.

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