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BACKGROUND: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. PATIENTS AND METHODS: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. RESULTS: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). CONCLUSION: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.
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BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Terapia Neoadjuvante/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Taxa de Sobrevida , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esofagectomia/mortalidade , Prognóstico , Seguimentos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Resposta Patológica CompletaRESUMO
Using functionalized supporting materials for the immobilization of molecular catalysts is an appealing strategy to improve the efficiency of molecular electrocatalysis. Herein, we report the covalent tethering of cobalt porphyrins on phenolic resins (PR) for improved electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). A cobalt porphyrin bearing an alkyl bromide substituent was covalently tethered on phenolic resins, through the substitution reaction of alkyl bromides with phenolic hydroxyl groups, to afford molecule-engineered phenolic resins (Co-PR). The resulted Co-PR was efficient for electrocatalytic ORR and OER by displaying an ORR half-wave potential of E1/2=0.78â V versus RHE and an OER overpotential of 420â mV to get 10â mA/cm2 current density. We propose that the many residual phenolic hydroxyl groups on PR will surround the tethered Co porphyrin and play critical roles in facilitating proton and electron transfers. Importantly, Co-PR outperformed unmodified PR and PR loaded with Co porphyrins through simple physical adsorption (termed Co@PR). The zinc-air battery assembled using Co-PR displayed a performance comparable to that using Pt/C+Ir/C. This work is significant to present phenolic resins as a functionalized material to support molecular electrocatalysts and demonstrate the strategy to improve molecular electrocatalysis with the use of phenolic resin residues.
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The front cover artwork is provided by Rui Cao's group at Shaanxi Normal University. The image shows the design of Co-porphyrin-engineered phenolic resins with intramolecular phenolic hydroxyl groups to facilitate proton and electron transfers for efficient oxygen electrocatalysis, which is bioinspired by cytochrome c oxidases, and shows the excellent performance of Zn-air batteries assembled with the hybrid material. Read the full text of the Research Article at 10.1002/cphc.202400017.
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Recent decades have seen increasing interest in developing highly active and selective electrocatalysts for the oxygen reduction reaction (ORR). The active site environment of cytochrome c oxidases (CcOs), including electrostatic and hydrogen-bonding interactions, plays an important role in promoting the selective conversion of dioxygen to water. Herein, we report the synthesis of three CoIII corroles, namely 1 (with a 10-phenyl ortho-trimethylammonium cationic group), 2 (with a 10-phenyl ortho-dimethylamine group) and 3 (with a 10-phenyl para-trimethylammonium cationic group) as well as their electrocatalytic ORR activities in both acidic and neutral solutions. We discovered that 1 is much more active and selective than 2 and 3 for the electrocatalytic four-electron ORR. Importantly, 1 showed ORR activities with half-wave potentials at E1/2 = 0.75 V versus RHE in 0.5 M H2SO4 solutions and at E1/2 = 0.70 V versus RHE in neutral 0.1 M phosphate buffer solutions. This work is significant for outlining a strategy to increase both the activity and selectivity of metal corroles for the electrocatalytic ORR by introducing cationic units.
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The molecular structure, electrochemistry, spectroelectrochemistry and electrocatalytic oxygen reduction reaction (ORR) features of two CoII porphyrin(2.1.2.1) complexes bearing Ph or F5 Ph groups at the two meso-positions of the macrocycle are examined. Single crystal X-ray analysis reveal a highly bent, nonplanar macrocyclic conformation of the complex resulting in clamp-shaped molecular structures. Cyclic voltammetry paired with UV/Vis spectroelectrochemistry in PhCN/0.1â M TBAP suggest that the first electron addition corresponds to a macrocyclic-centered reduction while spectral changes observed during the first oxidation are consistent with a metal-centered CoII /CoIII process. The activity of the clamp-shaped complexes towards heterogeneous ORR in 0.1â M KOH show selectivity towards the 4e- ORR pathway giving H2 O. DFT first-principle calculations on the porphyrin catalyst indicates a lower overpotential for 4e- ORR as compared to the 2e- pathway, consistent with experimental data.
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BACKGROUND: Imaging examinations, such as ultrasonography, magnetic resonance imaging and computed tomography scans, play key roles in healthcare settings. To assess and improve the quality of imaging diagnosis, we need to manually find and compare the pre-existing reports of imaging and pathology examinations which contain overlapping exam body sites from electrical medical records (EMRs). The process of retrieving those reports is time-consuming. In this paper, we propose a convolutional neural network (CNN) based method which can better utilize semantic information contained in report texts to accelerate the retrieving process. METHODS: We included 16,354 imaging and pathology report-pairs from 1926 patients who admitted to Shanghai Tongren Hospital and had ultrasonic examinations between 1st May 2017 and 31st July 2017. We adapted the CNN model to calculate the similarities among the report-pairs to identify target report-pairs with overlapping body sites, and compared the performance with other six conventional models, including keyword mapping, latent semantic analysis (LSA), latent Dirichlet allocation (LDA), Doc2Vec, Siamese long short term memory (LSTM) and a model based on named entity recognition (NER). We also utilized graph embedding method to enhance the word representation by capturing the semantic relations information from medical ontologies. Additionally, we used LIME algorithm to identify which features (or words) are decisive for the prediction results and improved the model interpretability. RESULTS: Experiment results showed that our CNN model gained significant improvement compared to all other conventional models on area under the receiver operating characteristic (AUROC), precision, recall and F1-score in our test dataset. The AUROC of our CNN models gained approximately 3-7% improvement. The AUROC of CNN model with graph-embedding and ontology based medical concept vectors was 0.8% higher than the model with randomly initialized vectors and 1.5% higher than the one with pre-trained word vectors. CONCLUSION: Our study demonstrates that CNN model with pre-trained medical concept vectors could accurately identify target report-pairs with overlapping body sites and potentially accelerate the retrieving process for imaging diagnosis quality measurement.
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Algoritmos , Registros Eletrônicos de Saúde , Armazenamento e Recuperação da Informação/métodos , Redes Neurais de Computação , Humanos , Patologia , Curva ROC , Semântica , UltrassonografiaRESUMO
To investigate the association between store-operated Ca2+ entry (SOCE) and reactive oxygen species (ROS) during hypoxia, this study determined the changes of transient receptor potential canonical 1 (TRPC1) and Orai1, two candidate proteins for store-operated Ca2+ (SOC) channels and their gate regulator, stromal interaction molecule 1 (STIM1), in a hypoxic environment and their relationship with ROS in pulmonary arterial smooth muscle cells (PASMCs). Exposure to hypoxia caused a transient Ca2+ spike and subsequent Ca2+ plateau of SOCE to be intensified in PASMCs when TRPC1, STIM1, and Orai1 were upregulated. SOCE in cells transfected with specific short hairpin RNA (shRNA) constructs was almost completely eliminated by the knockdown of TRPC1, STIM1, or Orai1 alone and was no longer affected by hypoxia exposure. Hypoxia-induced SOCE enhancement was further strengthened by PEG-SOD but was attenuated by PEG-catalase, with correlated changes to intracellular hydrogen peroxide (H2O2) levels and protein levels of TRPC1, STIM1, and Orai1. Exogenous H2O2 could mimic alterations of the interactions of STIM1 with TRPC1 and Orai1 in hypoxic cells. These findings suggest that TRPC1, STIM1, and Orai1 are essential for the initiation of SOCE in PASMCs. Hypoxia-induced ROS promoted the expression and interaction of the SOC channel molecules and their gate regulator via their converted product, H2O2.
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Canais de Cálcio/metabolismo , Cálcio/metabolismo , Peróxido de Hidrogênio/farmacologia , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Animais , Catalase/metabolismo , Células Cultivadas , Técnicas de Silenciamento de Genes , Hipóxia/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Polietilenoglicóis/metabolismo , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Superóxido Dismutase/metabolismo , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
microRNAs are a class of small non-coding RNA molecules negatively regulating gene expression at post-transcriptional level in many tissues including the central nervous system. cAMP response element binding protein (CREB) is a key nuclear factor highly expressed in hippocampal neurons on which many signal pathways converge. Recent studies have found that microRNA-181a is rich in mature nerve cells, and bioinformatics analysis shows that the CREB1 mRNA 3'-untranslated region (3'UTR) contains complementary sequence to the miR-181a seed region. In this study, we investigated whether miR-181a is a negative regulator for CREB1 expression in neurons. It was found that the expression of miR-181a was negatively correlated with Insulin-like growth factor-1 (IGF-1) and CREB1 in the Lewis rat hippocampus. miR-181a bound to CREB1 mRNA through a specific binding site in the 3'UTR sequence. The expression of CREB1 in PC12 cells was down-regulated by transfection with a miR-181a mimic and up-regulated by a miR-181a inhibitor. A down-regulated miR-181a and an up-regulated CREB1 were observed in IGF-1-stimulated PC12 cells. And miR-181a inhibited dendritic growth of cultured hippocampus neurons. These suggest that miR-181a is involved in IGF-1-regulated CREB1 expression by targeting its mRNA 3'UTR. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and are involved in the central nervous system development. Here, we demonstrate that miR-181a can inhibit the expression of the transcription factor CREB1 by specifically targeting its mRNA 3'UTR and inhibit the development of hippocampus neurons. Repressed expression of miR-181a is involved in IGF-1-mediated up-regulation of CREB1 in vivo and in vitro. These findings indicate that miR-181a could be a potential target for preventing neurodegenerative diseases.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Fator de Crescimento Insulin-Like I/fisiologia , MicroRNAs/fisiologia , Regiões 3' não Traduzidas/genética , Animais , Animais Recém-Nascidos , Western Blotting , Biologia Computacional , Dendritos/efeitos dos fármacos , Feminino , Imunofluorescência , Genes Reporter , Vetores Genéticos , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Luciferases/metabolismo , Masculino , Análise em Microsséries , Células PC12 , Gravidez , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
Invited for this month's cover is the group of Rui Cao at Shaanxi Normal University. The image shows the effects of through-space electrostatic interactions on the hydrogen evolution reaction. The Research Article itself is available at 10.1002/cssc.202200086.
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Elucidating the effects of various structural components on energy-related small molecule activation is of fundamental and practical significance. Herein the inhibition effect of positively charged substituents on the hydrogen evolution reaction (HER) was reported. With the use of Cu porphyrins 1-5 containing different numbers and locations of positively charged substituents, it was demonstrated that their electrocatalytic HER activities significantly decreased when more cationic units were located close to the Cu ion: the icat /ip (icat is the catalytic peak current, ip is the one-electron reduction peak current) value decreased from 38 with zero cationic unit to 15 with four closely located cationic units. Inspired by this result, Cu porphyrin 6, with four meso-phenyl groups each bearing a negatively charged para-sulfonic substituent, was designed. With these anionic units, 6 outperformed the other Cu porphyrins for electrocatalytic HER under the same conditions.
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Hidrogênio , Porfirinas , Cátions , Elétrons , Porfirinas/química , Eletricidade EstáticaRESUMO
Developing electrocatalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is of great importance. Herein, Co tetrakis(pentafluorophenyl)porphyrin (Co-P) and Fe chloride tetrakis(pentafluorophenyl)porphyrin (Fe-P) were loaded on carbon nanotubes (CNTs) for combining the electrocatalytic advantages of both Co-P and Fe-P. The resultant (Co-P)0.5(Fe-P)0.5@CNT composite displayed significantly boosted activity for the selective four-electron ORR with a half-wave potential of 0.80 V versus reversible hydrogen electrode (RHE) and for the OER with a potential of 1.65 V versus RHE to obtain 10 mA cm-2 current density in 0.1 M KOH. A Zn-air battery assembled from (Co-P)0.5(Fe-P)0.5@CNT exhibited a small charge-discharge voltage gap of 0.74 V at 2 mA cm-2, a high power density of 174.5 mW cm-2 and a good rechargeable stability (>120 cycles).