Cost-effectiveness analysis of tumor-infiltrating lymphocytes biomarkers guiding chemotherapy de-escalation in early triple-negative breast cancer.

BACKGROUND: To accelerate the clinical translation of tumor-infiltrating lymphocytes (TILs) biomarkers for guiding chemotherapy de-escalation in early-stage triple-negative breast cancer (TNBC), cost-effectiveness evidence is essential but has not been investigated. We intend to evaluate the cost-effectiveness of using TILs to guiding chemotherapy de-escalation in patients with early-stage TNBC from the perspective of the Chinese health service system. METHODS: The hybrid decision-tree-Markov model was designed to compare the cost-effectiveness of cytotoxic chemotherapy guided by whether TILs assay was performed in 50-year-old female patients with early-stage TNBC over a lifetime horizon. In Strategy (1), if TILs testing was performed, patients with TILs values exceeding 30% could be spared from chemotherapy. In Strategy (2), where no TILs testing was performed, all patients were administered chemotherapy following China's clinical practices. Based on the algorithm built by Guyot, the individual patient data were reconstructed from the published Kaplan-Meier curves, and the survival functions were calculated by parametric methods. Cost estimates were valued in Chinese yuan (as per rates in 2022). RESULTS: In 50-year-old female patients with early-stage TNBC, Strategy (1), which employs TILs testing to guide cytotoxic chemotherapy yielded an additional 0.47 quality-adjusted life years (QALYs) and saved 40,976 yuan, with an incremental cost-effectiveness ratio (ICER) of -87,182.98 yuan per QALY gained compared with Strategy (2). This indicates that compared with Strategy (2), Strategy (1) is the dominant scheme. The results were sensitive to utility parameters, discount rates, and treatment costs after relapse. At a willingness-to-pay threshold of 85,700 yuan (based on GDP per capita) per QALY, the probability of TILs being cost-effective was almost 100%. CONCLUSIONS: The application of biomarkers (TILs) to guide decisions for chemotherapy de-escalation is a cost-effective strategy for early-stage TNBC patients and deserves to be widely promoted in clinical practice.

Lightweight and flexible PAN@PPy/MXene films with outstanding electromagnetic interference shielding and Joule heating performance.

Lightweight and flexible multifunctional materials with excellent electromagnetic interference (EMI) shielding and Joule heating performances are highly demanded for smart and wearable electronics. In this work, polyacrylonitrile (PAN) nanofiber films are prepared by electrospinning and then coated with polypyrrole (PPy) via vapor deposition, yielding a continuous three-dimensional (3D) conductive network of PAN@PPy. Ti3C2Tx MXene nanosheets with high electrical conductivity are sprayed on the PAN@PPy film to enhance its EMI shielding performance. The as-prepared PAN@PPy/MXene films (55 µm thick) exhibit a high EMI shielding effectiveness (SE) of 32 dB, achieving an extraordinarily high normalized surface-specific SE (SSE/t) of up to 17 534.5 dB cm2 g-1 from 8.2 to 12.4 GHz; simultaneously, the temperatures of PAN@PPy/MXene films can be driven up to 170.5 °C at an input voltage of 4 V, and exhibit fast-response, stable, and long-term Joule heating performance. The high SSE/t and efficient Joule heating ability of the films bode potential applications in smart and wearable devices.

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis.

BACKGROUND: This meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR). METHODS: A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521). RESULTS: A total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50-4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93-6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67-4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03-14.1, P = 0.78). CONCLUSIONS: Increased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.

A multidimensional nanostructural design towards electrochemically stable and mechanically strong hydrogel electrodes.

Electrically conductive hydrogels are polymeric composites that combine electroactive fillers with hydrogel networks. They offer an electrically conductive pathway for electron transfer and provide an interconnected framework for ion diffusion, as well as an extended active interface for redox reactions, being ideal frameworks to design and construct flexible electrodes. In this work, we integrate nanoscale building blocks into a unique ternary (1, 2 and 3 dimensional) hydrogel architecture, where conductive polymer polypyrrole (PPy) nanofibers (1D) and MXene nanosheets (2D) are uniformly dispersed in polyvinyl alcohol (PVA) matrixes (3D). 1D nanofibers and 2D nanosheets were found to greatly increase the mechanical properties of the hydrogel hosts, demonstrating a remarkable tensile strength of 10.3 MPa and a large elongation over 380%. Moreover, the as-fabricated hierarchical structure effectively promotes electrolyte diffusion, exhibiting exceptional capacitive characteristics, including a high gravimetric specific capacitance of 614 F g-1 (at 1 A g-1) and an unprecedented cycling stability (100% capacitance retention over 10 000 cycles). A solid-state supercapacitor is assembled based on these MXene/PPy-PVA hydrogels, which demonstrates an efficient approach to the fabrication of wearable energy storage devices.

Dexmedetomidine pretreatment attenuates isoflurane-induced neurotoxicity via inhibiting the TLR2/NF-κB signaling pathway in neonatal rats.

Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity, while Dexmedetomidine (Dex) has significant neuroprotective effects. In our study, we explored the effects of Dex on isoflurane-induced neurotoxicity through the TLR2/NF-κB signaling pathway. Seven-day old neonatal Sprague-Dawley rats pretreated with 25, 50, 75 µg/kg Dex were exposed to 0.75% isoflurane for 6 h. Spatial learning and memory abilities were detected by Morris water maze test. Ultrastructure of hippocampal neurons, neuronal apoptosis, and the levels of TLR2/NF-κB signaling pathway-related factors were determined. Besides, TLR2 agonist Pam3CSK4 or NF-κB inhibitor BAY11-7082 was injected to further validate the involvement of TLR2/NF-κB signaling following Dex treatment. Consequently, we found isoflurane inhalation resulted in increased cell apoptosis, inflammation and TLR2/NF-κB signaling pathway activation, and decreased PSD95 expression and spatial learning and memory abilities. Dex led to decreased inflammation, improved neuronal structure and viability in rats as well as enhanced spatial learning and memory abilities of rats, and it inactivated the TLR2/NF-κB signaling pathway. Additionally, Pam3CSK4 injection reversed the protective effects of Dex on isoflurane-induced neurotoxicity. In conclusion, this study provided evidence that Dex could alleviate isoflurane-induced neurotoxicity through inhibition of the TLR2/NF-κB signaling pathway. The findings may offer novel insights for the clinical usage of anesthetics.

LncRNA SNHG8 promotes proliferation and invasion of gastric cancer cells by targeting the miR-491/PDGFRA axis.

This study aimed to investigate the effects of long non-coding small nucleolar RNA host gene 8 (SNHG8) on the proliferation and invasion of gastric cancer (GC). The GC tissues and adjacent normal tissues from 30 patients were collected. Human GC cell lines, including AGS, SGC-7901, MKN-1, and BGC-803 and normal human gastric epithelial cell line GES-1 were purchased and cultured. The Cell Counting Kit-8 and Western blots were used to access cell proliferation, and platelet-derived growth factor receptor α (PDGFRA) expression, respectively. qRT-PCR was used to evaluate the expression of SNHG8 and miRNA-491. A transwell assay was applied to evaluate cell invasion. This study illustrated that SNHG8 expression was upregulated in GC tissues, as well as in cell lines. Moreover, knockdown of SNHG8 inhibited GC cell proliferation and invasion. Significantly, we determined that miRNA-491 was not only downregulated in stomach cancer but also inhibited GC cell progression induced by SNHG8. Further investigation demonstrated that SNHG8 promoted the proliferation and invasion of GC cells by targeting the miR-491/PDGFRA axis. LncRNA SNHG8 promoted the proliferation and invasion of GC cells by targeting the miR-491/PDGFRA axis, which might provide new insight for potential therapeutic strategies for GC in the future.