Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.

Background Alterations in serum creatinine levels delay the identification of severe cardiac surgery‐associated acute kidney injury. To provide timely diagnosis, novel predictive tools should be investigated. Methods and Results This prospective observational study consists of a screening cohort (n=204) and a validation cohort (n=198) from 2 centers from our hospital. Thirty‐two inflammatory cytokines were measured via a multiplex cytokine assay. Least absolute shrinkage and selection operator regression was conducted to select the cytokine signatures of severe cardiac surgery‐associated acute kidney injury. Afterwards, the significant candidates including interferon‐γ, interleukin‐16, and MIP‐1α (macrophage inflammatory protein‐1 alpha) were integrated into the logistic regression model to construct a predictive model. The predictive accuracy of the model was evaluated in these 2 cohorts. The cytokine‐based model yielded decent performance in both the screening (C‐statistic: 0.87, Brier 0.10) and validation cohorts (C‐statistic: 0.86, Brier 0.11). Decision curve analysis revealed that the cytokine‐based model had a superior net benefit over both the clinical factor‐based model and the established plasma biomarker‐based model for predicting severe acute kidney injury. In addition, elevated concentrations of each cytokine were associated with longer mechanical ventilation times, intensive care unit stays, and hospital stays. They strongly predicted the risk of composite events (defined as treatment with renal replacement therapy and/or in‐hospital death) (OR of the fourth versus the first quartile [95% CI]: interferon‐γ, 27.78 [3.61–213.84], interleukin‐16, 38.07 [4.98–291.07], and MIP‐1α, 9.13 [2.84–29.33]). Conclusions Our study developed and validated a promising blood cytokine‐based model for predicting severe acute kidney injury after cardiac surgery and identified prognostic biomarkers for assisting in outcome risk stratification.

Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC), but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) GC cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern (higher at zeitgeber time 6, lower at zeitgeber time 18). Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of peroxisome proliferator-activated receptor γ (PPARγ) and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at zeitgeber time 6 significantly improved trastuzumab efficacy in GC. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in GC.

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.

Purpose: To quantitatively evaluate the effect of preexisting diabetes mellitus (DM) on the outcomes of patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Observational studies comparing the prognosis of NSCLC patients with and without diabetes were identified from PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials (CENTRAL). We searched for studies that published in English from inception to March 30, 2019, using search terms related to diabetes and NSCLC. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated by a random-effect model and subgroup analyses were performed. Results: In all, 17 of 1475 identified studies were finally included in the meta-analysis. The result revealed that preexisting diabetes had a significantly negative impact on the overall survival (OS) of patients with NSCLC (HR: 1.31, 95% CI: 1.12-1.54), especially in patients undergoing surgical treatment (HR: 1.46, 95% CI: 1.02-2.09) in comparison with those receiving only non-surgical treatment (HR: 1.33, 95% CI: 0.87-2.03). In addition, preexisting diabetes was more likely to be associated with a worse prognosis among Asian NSCLC patients than Western patients. Sensitivity analysis indicated that the main result was robust, and no evidence of publication bias was found. Conclusion: Preexisting DM has a negative impact on diabetic NSCLC patients' prognosis.

Background: Intrathoracic anastomotic leakage (IAL) remains a major complication of esophagectomy.Main non-surgical options of management include chest drainage and endoscope interventions. This study is aim to present our experience and assess the efficacy of endoscopic naso-leakage drainage (ENLD) in patients with IAL. Methods: From June 2011 to January 2017, 67 patients who developed IAL after esophagectomy and managed by non-surgical approaches were analyzed retrospectively. IAL was confirmed by clinical presentations combined with the evidence of CT scan, radiography and endoscopy. Thirty-eight patients were treated by conventional chest drainage (CD group) and 29 patients underwent ENLD with or without chest drainage (ENLD group), while other treatments including enteral nutrition and antibiotics had no difference between the two groups. In ENLD group, a 12 Fr naso-leakage tube was placed through the leakage to the bottom of vomica under ultra-slim electronic gastroscope. The naso-leakage tube was then connected to a gastrointestinal decompression device for drainage and was also used for rinse. When the vomica diminished and the drainage was also clean, the naso-leakage tube could be pulled back gradually. Finally, healing of the leakage was confirmed endoscopically. Clinical records of the two groups were analyzed.Results: In ENLD group, naso-leakage tubes were successfully placed under endoscope in all 29 patients without any procedure-related complications. In CD group, the mortality is 7.9% (three patients) and five patients (13.2%) developed to systemic inflammatory response syndrome (SIRS) due to insufficient drainage.While in ENLD group, there was only one patient (3.4%) developed to SIRS and no death was observed, but the difference was not statistically significant. When compared with the CD group, the ENLD group had a shorter healing course (44.2±18.3 vs. 60.5±27.7 days, P=0.008), duration of antibiotics usage (16.4±7.8 vs.11.8±3.8 days, P<0.001) and duration of fever (4.3±2.2 vs. 9.5±8.6 days, P=0.002). Conclusions: To our initial experience, ENLD is an ideal option with safety and efficacy in management of IAL after esophagectomy.

Background: Lymph node ratio (LNR), defined as the ratio of the number of positive lymph nodes to the total of all resected nodes, has been reported to be a predictor of survival of patients with several types of cancer. However, the prognostic value of LNR and other factors in patients with resected N2 stage lung squamous cell carcinoma has never been considered. Methods: Data from 1778 patients with resected N2 stage lung squamous cell carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff value of LNR was identified by X-tile. A multivariable Cox model and corresponding nomogram were constructed to predict overall survival (OS) and cancerspecific survival (CSS). Both the cutoff value of LNR and the model were further validated in 146 similar patients treated in Zhongshan Hospital. Heat maps were created to visualize the distribution of LNR and the number of positive lymph nodes with the predicted survival probabilities. Results: The optimal cutoff value for LNR was identified as 0.42. Multivariable analysis showed that age, sex, tumor laterality, type of surgery, T stage, chemotherapy and LNR were independently correlated with OS. Harrell's C-index of the nomogram (0.64) was significantly higher than the index of the T stage-based model (0.54). Calibration curves showed good agreement between predicted and observed survival probabilities. The robustness of the model was also demonstrated by external validation. Conclusion: LNR less than 0.42 was associated with improved OS and CSS for patients with resected N2 stage lung squamous cell carcinoma.

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