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Organelle-targeted photosensitizers (PSs) have demonstrated enhanced phototherapeutic effect by specifically destroying subcellular organelle. As a critical cellular organelle, the cell membrane plays crucial roles in maintaining cell integrity and regulating cellular communications. To date, a variety of membrane-targeted PSs have been developed and shown exceptional therapeutic effects. However, functional PSs that can achieve membrane-targeted photodynamic therapy (PDT) and real-time monitor the therapeutic process have rarely been reported. In particular, the development of self-reporting PS with near-infrared (NIR) absorption is highly desirable but remains a challenge. Herein, we presented two molecular rotor-based self-reporting PSs. One of the PSs, MRMP-2, possesses NIR absorption property, making it a promising candidate for clinical applications. These PSs could not only enable membrane-targeted PDT but also demonstrate selective fluorescence response toward viscosity. In this regard, the fluorescence variation of these PSs could be utilized to indicate the disruption of membrane structure during PDT process. By leveraging the feedback of the fluorescence signal, we could make intuitive judgement about the phototherapeutic results. As a result, these two PSs possess significant potential in the field of imaging-guided PDT.
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CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator (BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.
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Doença Hepática Terminal , Hepatite B Crônica , Humanos , Vírus da Hepatite B , Hepatite B Crônica/complicações , Linfócitos T CD8-Positivos , Leucócitos Mononucleares , Subpopulações de Linfócitos T , Progressão da DoençaRESUMO
INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia Neoadjuvante , Carcinoma de Células Escamosas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
As an effective targeted therapy for advanced hepatocellular carcinoma (HCC), sorafenib resistance has been frequently reported in recent years, with the activation of autophagy by cancer cells under drug stress being one of the crucial reasons. Sorafenib treatment could enhance autophagy in HCC cells and autophagy is also considered as an important mechanisms of drug resistance. Therefore, the inhibition of autophagy is a potential way to improve the sensitivity and eliminate drug resistance to restore their efficacy. To determine whether autophagy is involved in sorafenib resistance and investigate its role in the regulation of HepG2 cells' (an HCC cell line) chemosensitivity to sorafenib, we simultaneously treated HepG2 with sorafenib and 3-Methyladenine (3-MA) (a common autophagy inhibitor). First, by performing cell counting kit 8 cell viability assay, Hoechst 33342 apoptosis staining, and Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis kit detection, we found that both sorafenib and 3-MA effectively inhibitted the proliferative activity of HepG2 cells and induced their apoptosis to a certain extent. This effect was significantly enhanced after these two drugs were combined, which was also confirmed by the increased expression of apoptosis-related proteins. Subsequently, by using AAV-GFP-LC3 transfection methods and transmission electron microscopy, we found that both the number and activity of autophagosomes in HepG2 cells in sorafenib and 3-MA group were significantly reduced, suggesting that autophagy activity was inhibited, and this result was consistent with the expression results of autophagy-related proteins. Therefore, we conclude that 3-MA may attenuate the acquired drug resistance of sorafenib by counteracting its induction of autophagy activity, thus enhancing its sensitivity to advanced HCC therapy.
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Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Adenina/administração & dosagem , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Sinergismo Farmacológico , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Sorafenibe/administração & dosagemRESUMO
Tuning the fluorescence of aggregation-induced emission (AIE)-based materials in a reversible way is essential and a requisite for their applications. The multiple host-guest interactions of polypseudorotaxanes (PPRs) could alter the aggregation state of hydrophobic AIE-based polymeric materials and consequently switch the fluorescence. Herein, tetraphenylethylene (TPE) as a typical AIE molecule has been incorporated into the main chains of the guest polyurethane via a step condensation between poly(ethylene glycol) (PEG)-based dicarbonate and TPE-diamine along with the cleavable disulfide bonds. γ-Cyclodextrins (γ-CDs) can selectively recognize the TPE units at the polyurethane chains to afford a PPR. Hydrophilic PEG segments and γ-CD molecules in the PPR could promote the disaggregation of TPE units, suppressing the fluorescence emission of TPE. To restore the aggregated state and fluorescence of TPE units, tris(2-carboxyethyl)phosphine (TCEP) and α-amylase are sequentially introduced to cleave the disulfide bonds and cut α-1,4 glycosidic bonds of γ-CD, reactivating the AIE behavior of PPR tandemly and accomplishing the reversible cycle of tuning the fluorescence of TPE. The present study provides a tandem way to switch the AIE behavior of polymeric materials reversibly.
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Polímeros , Estilbenos , Fluorescência , PolietilenoglicóisRESUMO
In this article, we present an ultra-sensitive and ratiometric fluorescent probe (TR-Hg) for Hg2+ detection based on the mechanism of aggregation induced emission (AIE) and dark through-bond energy transfer (DTBET). The probe was constructed using tetraphenylethene as the dark donor and rhodamine B thiolactone as the acceptor. By exploiting the advantages of DTBET, which eliminates emission leakage from dark donors and provides nearly 100% energy transfer efficiency, TR-Hg exhibits more than a 30 000-fold fluorescence ratio enhancement after reacting with Hg2+. TR-Hg demostrates (i) a detection limit of 43 pM, which is the lowest among the reported ratiometric Hg2+ probes, (ii) excellent selectivity, fast response-time (<10 s) and a wide pH application range, (iii) strong applicability for paper-based colorimetric assay, where readout can be performed by the naked eye, and (iv) fluorescent imaging of Hg2+ in onion epidermal tissues, indicating its potential use in living organisms.
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Infection with hepatitis B virus (HBV) e-antigen (HBeAg)-negative strains is increasingly prevalent. Currently, detailed information of the obtained natural HBV strain is not available except for the B genotype and HBeAg-negative. The aim of the present study was to characterize the natural genetic variation of the HBeAg-negative strain and investigate its function. The genic sequence was determined using Sanger sequencing, and compared to related sequences using alignment and phylogenetic analysis. In vivo, virus-specific serum markers were investigated in CBA/CaJ mice. The sequence had a full genome length of 3215 nucleotides. Sites 122, 125, 127, and 160 in S regions were identified as lysine, threonine, proline, and lysine respectively. The main four point variants including A1762T, G1764A, G1896A, and G1899A were detected in the full-length genome. The genotype of the sequence was B, with sub-genotype B2 and serological subtype adw2. The characterize of the natural genetic variation strain showed no reported drug-resistant variant in P region and no reported immune escape site in S region. The strain will increase viral replication and infection for mutations A1762T and G1764A in the basal core promoter region, and mutations G1896A and G1899A in the pre-core region. The G1896A variant resulted in a premature stop codon and abolished HBeAg expression. HBsAg persisted for 26 weeks and HBeAg was still negative in CBA/CaJ mice. The present sequence is representative of the HBeAg-negative genome and may serve as a valuable reference for studying HBeAg-negative strains. The present findings were successfully verified in CBA/CaJ mice, demonstrating good applicability of the sequence.
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DNA Viral/genética , Genoma Viral , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Animais , DNA Circular/genética , DNA Circular/imunologia , DNA Viral/imunologia , Modelos Animais de Doenças , Variação Genética , Genótipo , Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Mutação , Regiões Promotoras Genéticas , Padrões de Referência , Análise de Sequência de DNA , Replicação ViralRESUMO
Histone deacetylases (HDACs) play important roles in regulating various physiological and pathological processes. Developing fluorescent probes capable of detecting HDAC activity can help further elucidate the roles of HDACs in biology. In this study, we first developed a set of activity-based fluorescent probes by incorporating the Kac residue and the O-NBD group. Upon enzymatic removal of the acetyl group in the Kac residue, the released free amine reacted intramolecularly with the O-NBD moiety, resulting in turn-on fluorescence. These designed probes are capable of detecting HDAC activity in a continuous fashion, thereby eliminating the extra step of fluorescence development. Remarkably, the amount of turn-on fluorescence can be as high as 50-fold, which is superior to the existing one-step HDAC fluorescent probes. Inhibition experiments further proved that the probes can serve as useful tools for screening HDAC inhibitors. Building on these results, we moved on and designed a dual-purpose fluorescent probe by introducing a diazirine photo-cross-linker into the probe. The resulting probe was not only capable of reporting enzymatic activity but also able to directly identify and capture the protein targets from the complex cellular environment. By combining a fluorometric method and in-gel fluorescence scanning technique, we found that epigenetic readers and erasers can be readily identified and differentiated using a single probe. This is not achievable with traditional photoaffinity probes. In light of the prominent properties and the diverse functions of this newly developed probe, we envision that it can provide a robust tool for functional analysis of HDACs and facilitate future drug discovery in epigenetics.
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Corantes Fluorescentes/química , Histona Desacetilases/análise , Proteômica , Corantes Fluorescentes/síntese química , Histona Desacetilases/metabolismo , Humanos , Estrutura MolecularRESUMO
A series of new fluorogenic probes for monoamine oxidases (MAOs) were reported based on an oxidation and ß-elimination mechanism. The limits of detection of the probes for MAO-A and -B were determined to be 3.5 and 6.0 µg mL(-1) respectively. These probes displayed strong activity towards MAOs, especially MAO-B. Cellular imaging studies were also successfully conducted with MCF-7 cells.
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Corantes Fluorescentes/química , Monoaminoxidase/análise , Xantenos/química , Ativação Enzimática , Humanos , Células MCF-7 , Estrutura Molecular , Monoaminoxidase/metabolismoRESUMO
Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy's design.
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BACKGROUND: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. METHODS: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3â +â AEs). RESULTS: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HRâ =â 0.80; 95% CI: 0.68-0.94), PFS (HRâ =â 0.78; 95% CI: 0.66-0.93), pCR (ORâ =â 13.00; 95% CI: 7.82-21.61) and R0 resection (ORâ =â 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (ORâ =â 2.31; 95% CI: 1.26-4.25) and grade 3â +â AEs (ORâ =â 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (ORâ =â 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HRâ =â 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HRâ =â 0.80; 95% CI: 0.63-1.08). CONCLUSIONS: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3â +â AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.
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Adenocarcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adenocarcinoma/cirurgia , QuimiorradioterapiaRESUMO
BACKGROUND: Sarcoma is a heterogeneous malignancy arising from interstitial tissue. Anthracycline-based therapy is the first-line treatment recommended by guidelines for patients with locally advanced or metastatic unresectable sarcoma. Recently, targeted therapies, in particular tyrosine kinase inhibitors (TKIs), have made significant progress in the treatment of sarcoma, and their efficacy has been investigated in randomized controlled trials. The aim of this meta-analysis is to evaluate the efficacy of TKIs in patients with advanced or metastatic sarcoma who have previously received chemotherapy. METHODS: We completed a meta-analysis after conducting literature searches in PubMed, Embase, and Cochrane. The single-drug, placebo-controlled, randomized controlled clinical trials of TKIs in patients with advanced or progressive sarcoma who have previously received chemotherapy are available for inclusion in the study. The observation results were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The subgroup analysis was performed according to histological subtypes of sarcoma. RESULTS: This study included 6 studies, including 1033 patients. The ORR (OR: 7.99, 95% CI: 3.62-19.61, Pâ <â .00001), DCR (OR: 2.54, 95% CI: 1.27-5.08, Pâ =â .009), PFS (HR: 0.46, 95% CI: 0.34-0.62, Pâ <â .00001), and OS (HR: 0.80, 95% CI: 0.67-0.96, Pâ =â .02) of patients treated with TKIs were better than those in the placebo group. CONCLUSIONS: In patients with advanced sarcoma, TKIs have been shown to have advantages in terms of ORR, DCR and PFS and OS. Multi-targeted TKIs may be considered as one of the second-line treatment options for sarcoma patients who have received prior chemotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Inibidores de Proteínas Quinases , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológicoRESUMO
Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).
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Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Terapia Neoadjuvante/métodos , Resultado do TratamentoRESUMO
BACKGROUND: As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. METHODS: mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. RESULTS: Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. CONCLUSIONS: Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
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Doença de Alzheimer , Amnésia Anterógrada , Colecistocinina , Camundongos Transgênicos , Receptor de Colecistocinina B , Animais , Camundongos , Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Amnésia Anterógrada/tratamento farmacológico , Colecistocinina/metabolismo , Modelos Animais de Doenças , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Colecistocinina B/genética , Receptor de Colecistocinina B/agonistas , Receptor de Colecistocinina B/deficiênciaRESUMO
To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.
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Camundongos Nus , Terapia Fototérmica , Animais , Terapia Fototérmica/métodos , Camundongos , Modelos Animais de Doenças , Humanos , Linhagem Celular Tumoral , Raios Infravermelhos/uso terapêutico , Neoplasias/terapiaRESUMO
The present study investigated the epidemiology and clinical characteristics of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and determined the risk factors for delayed discharge or release from isolation for pediatric patients in Quanzhou, China in 2022. There were 145, 254 and 23 patients in the asymptomatic, mildly symptomatic and moderately symptomatic categories, respectively. The proportion of pediatric patients in the moderately symptomatic category increased with increasing age. No child aged <1 year and 9.02% of patients aged 13-18 years were in the moderately symptomatic category. The proportion of patients with asymptomatic infection did not differ significantly by vaccination status. The median days until the first negative conversion of viral RNA was 11 days, and the median hospitalization duration was 16 days. Most symptoms appeared in the upper respiratory tract. Notably, ~33.23% of patients showed elevated aspartate aminotransferase levels. C-reactive protein and interleukin-6 (IL-6) levels, and lymphocyte counts were consistently lower in asymptomatic patients than those in in symptomatic patients. Adjusted logistic regression analyses indicated that IL-6 levels and time to the first negative conversion of viral RNA were independent risk factors for delayed discharge. The area under the curve of the regression model for predicting delayed discharge was 0.760. In conclusion, these results could facilitate the formulation of global epidemic prevention policies for pediatric patients.
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RATIONALE: Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports. PATIENT CONCERNS: A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit. DIAGNOSES: Ascending colon cecal junction carcinoma with prostate metastasis. INTERVENTIONS: Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate. OUTCOMES: At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.
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Carcinoma , Neoplasias do Ceco , Neoplasias do Colo , Neoplasias da Próstata , Masculino , Humanos , Idoso , Colo Ascendente/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias do Colo/cirurgia , Neoplasias do Ceco/cirurgiaRESUMO
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient's prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as "pseudoprogression" during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.
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The most common metastatic sites of gastric cancer include the liver, peritoneum, lung, and bone. However, there is a lack of relevant clinical reports regarding rectal metastasis. Herein, we report the rare case of a patient with gastric cancer who developed rectal metastasis. A 57-year-old male patient was diagnosed with gastric cancer and underwent a radical gastrectomy in January 2016, followed by eight cycles of adjuvant chemotherapy. The patient subsequently developed a rectal mass in March 2021. He was diagnosed with rectal adenocarcinoma and underwent surgical resection of the rectal tumor. A mass was then found in the abdominal wall in September 2021 and was resected. Specimens obtained from the three surgeries were reviewed, and the rectal tumor and the mass in the abdominal wall were both found to be metastatic tumors from the gastric cancer. Metastasis of gastric cancer to the rectum is rare, but it is important to differentiate between rectal metastasis and primary rectal cancer to help avoid unnecessary treatment.
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Neoplasias Retais , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Retais/patologia , Reto/patologia , Quimioterapia AdjuvanteRESUMO
Lysosomal viscosity is a significant parameter of lysosomes and closely related to various diseases. Herein, two fluorescent probes, Lyso-vis-A and Lyso-vis-B, were developed, which demonstrate diverse advantages, including great water solubility, lysosome targeting ability and viscosity sensitivity. In particular, Lyso-vis-A exclusively showed fluorescence response toward viscosity but was not influenced by pH changes, rendering it a selective lysosomal viscosity probe. Furthermore, Lyso-vis-A was successfully applied to monitor lysosomal viscosity variations in living cells and differentiate cancer cells and normal cells.