[Establishment and verification of a prognostic nomogram for survival of tongue squamous cell carcinoma patients who underwent cervical dissection].

OBJECTIVE: To evaluate the prognostic significance of inflammatory biomarkers, prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma (TSCC) patients who underwent cervical dissection. METHODS: The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018. The study population was divided into the training set and validation set by 7 :3 randomly. The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation score (SIS) and prognostic nutritional index (PNI). Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). The nomogram's accuracy was internally validated using concordance index, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration plot and decision curve analysis. RESULTS: According to the univariate Cox regression analysis, clinical TNM stage, clinical T category, clinical N category, differentiation grade, depth of invasion (DOI), tumor size and pre-treatment PNI were the prognostic factors of TSCC. Multivariate Cox regression analysis revealed that pre-treatment PNI, clinical N category, DOI and tumor size were independent prognostic factors for OS or DSS (P < 0.05). Positive neck nodal status (N≥1), PNI≤50.65 and DOI > 2.4 cm were associated with the poorer 5-year OS, while a positive neck nodal status (N≥1), PNI≤50.65 and tumor size > 3.4 cm were associated with poorer 5-year DSS. The concordance index of the nomograms based on independent prognostic factors was 0.708 (95%CI, 0.625-0.791) for OS and 0.717 (95%CI, 0.600-0.834) for DSS. The C-indexes for external validation of OS and DSS were 0.659 (95%CI, 0.550-0.767) and 0.780 (95%CI, 0.669-0.890), respectively. The 1-, 3- and 5-year time-dependent ROC analyses (AUC = 0.66, 0.71 and 0.72, and AUC = 0.68, 0.77 and 0.79, respectively) of the nomogram for the OS and DSS pronounced robust discriminative ability of the model. The calibration curves showed good agreement between the predicted and actual observations of OS and DSS, while the decision curve confirmed its pronounced application value. CONCLUSION: Pre-treatment PNI, clinical N category, DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC. The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection. They are effective tools for predicting survival and helps to choose appropriate treatment strategies to improve the prognosis.

Photocatalytic Phosphine-Mediated Thioesterification of Carboxylic Acids with Disulfides.

Herein, a practical and effective synthesis of thioesters from readily available carboxylic acids and odorless disulfides was developed under photocatalytic conditions. This approach involves phosphoranyl radical-mediated fragmentation to generate acyl radicals and allows for incorporation of both S atoms of the disulfides into the desired products. In addition to batch reactions, a continuous-flow reactor was employed, enabling rapid thioester synthesis on a gram scale. Preliminary experimental mechanistic studies and the rapid synthesis of dalcetrapib are also demonstrated.

Deoxygenation of oximes for the synthesis of pyrrolines via hydroimination cyclization.

Herein, we report the generation of iminyl radicals through photocatalytic deoxygenation of oximes with trivalent phosphine. The hydroimination reaction proceeded via ß-scission of a phosphoranyl radical, followed by 5-exo-trig cyclization of the resulting iminyl radical. This protocol transforms oximes, including alkyl oximes, into a variety of pyrrolines in moderate to good yields. A radical clock experiment confirmed the formation of a cyclic radical and supported our reaction design.

Photoredox Catalytic Phosphine-Mediated Deoxygenation of Hydroxylamines Enables the Construction of N-Acyliminophosphoranes.

The chemistry of phosphoranyl radicals has received increasing attention in recent years. Here, we report the generation of amidyl radicals through photocatalytic deoxygenation of hydroxylamines with triphenylphosphine. This methodology offers a novel and convenient route to a diverse range of N-acyliminophosphoranes in moderate to good yields under visible-light photoredox conditions. Fluorescence quenching experiments suggest that the excited-state of the organic photocatalyst (4CzIPN) was oxidatively quenched by a Cu(II) salt.

Generation of Oxyphosphonium Ions by Photoredox/Cobaloxime Catalysis for Scalable Amide and Peptide Synthesis in Batch and Continuous-Flow.

Phosphine-mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium intermediates for the subsequent nucleophilic additions. Through dual catalysis of photoredox and cobaloxime, we realized a radical strategy for the catalytic formation of acyloxyphosphonium ions that enables direct amidation. The deoxygenative protocol exhibits a broad scope and has been used in the late-stage amidation of drug molecules. In addition to batch reactions, a continuous-flow reactor was developed, enabling rapid peptide synthesis on gram scale. The successful assembly of a tetrapeptide on the solid support further demonstrated the versatility of this photocatalytic system. Moreover, experimental and computational studies are consistent with the hypothesis of acyloxyphosphonium ions being formed as the key intermediates.

Developing a predictive risk score for perioperative blood transfusion: a retrospective study in patients with oral and oropharyngeal squamous cell carcinoma undergoing free flap reconstruction surgery.

BACKGROUND: A simple and accurate scoring system to predict risk of blood transfusion in patients having surgical tumor resection with immediate free flap reconstruction primary surgery for oral and oropharyngeal squamous cell carcinoma (OOSCC) is lacking. Anticipating the blood transfusion requirements in patients with oral cancer is of great clinical importance. This research aimed to propose a valid model to predict transfusion requirements in patients undergoing surgery with free flap reconstruction for an OOSCC. METHODS: This retrospective study consisted of 385 patients who underwent oncologic surgery with immediate free flap reconstruction for locally advanced OOSCC from 2012 to 2019. The primary outcome measured was the exposure of patients to perioperative allogeneic blood transfusion. Based on a multivariate model of independent risk variables and their odds ratio, a blood transfusion risk score (TRS) was developed to predict the likelihood of the perioperative blood transfusion. The discriminatory accuracy of the model was evaluated using the area under the receiver operating characteristic (ROC) curve, and Youden index was used to identify the optimal cut-point. RESULTS: Logistic regression analyses identified lymph node status, preoperative hemoglobin (Hb) levels, bone resection, osseous free tissue transfer, and operative duration were identified as independent predictors of blood transfusion. A TRS integrating these variables was separated into three categories. The TRS assessed the transfusion risk with good predictive ability, with an overall area under the ROC curve (AUC) was 0.826. At the optimal cut-point of 5.5, the TRS had a sensitivity of 72.3% and a specificity of 78.2%. The ROC analysis showed that patients with a TRS of 5.5 or more had a greater requirement for perioperative transfusion. CONCLUSIONS: The use of the integer-based TRS allowed the identification of high-risk patients who may require perioperative transfusion undergoing tumor resection surgery for the treatment of OOSCC.

The Asymmetric A³(Aldehyde⁻Alkyne⁻Amine) Coupling: Highly Enantioselective Access to Propargylamines.

The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands enabled the highly enantioselective synthesis of chiral propargylamines, which are further used in the construction of nitrogen-containing chiral building blocks.

pH Dependent synthesis of two isomeric dinuclear Cerium(II) complexes: Structures, DNA interactions, cytotoxic activity and apoptotic study.

Two isomeric dinuclear Cerium(II) complexes 1 and 2, formulated as Ce2(phen)2(NO3)2(L)4 [L=phenylacetic acid, phen=1,10-phenanthroline] was synthesized under solvothermal conditions at different pH values. The two complexes were characterized by elemental analysis, IR and single crystal X-ray diffraction. Complexes 1 and 2 were studied the binding with DNA and against cytotoxic activity. Fluorescence analysis indicated that the two complexes can bind to DNA. The changes with different gradient concentration of DNA added into the complexes in absorption spectra show a strongπ-stacking interaction between the complexes and DNA base pairs. The Cerium(II) complexes showed good cytotoxic activity against cancer cell lines, being 2 the most potent complex. Apoptotic studies of the two novel dinuclear complexes showed significant inhibitory rate on cancer cell growth line KB.