Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer.

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.

Mental health and academic achievement among Chinese adolescents during COVID-19 pandemic: The mediating role of self-regulation learning.

The changes that COVID-19 pandemic has brought upon the world are unprecedented. Its impact on students' learning is equally profound, making it critical to heed students' academic achievement effects that may derive from these alterations. Therefore, the present study explored an integrative model of mental health, self-regulated learning and academic achievement among adolescents during the pandemic. Participants were 1001 senior high school students (Mage = 17.00, SDage = 0.78, 48.7% female) from China. Results showed that the degree to which students were mentally healthy was not significantly related to academic achievement, whereas academic achievement and mental health were positively associated with self-regulated learning. Following structural equation modelling analysis, the effect of mental health on academic achievement was fully mediated by self-regulated learning. Taken together, the findings emphasised the necessity of developing self-regulated learning strategies during public health emergencies and have clinical and educational implications for planning psychological interventions in order to improve mental health and academic performance as well.

STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.

MicroRNA­22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway.

Osteosarcoma (OS) is the most common primary malignant tumor of the bone affecting children and adolescents. Chemotherapy is now considered as a standard component of OS treatment, not only for children, but also for adults. However, chemoresistance continues to pose a challenge to therapy. Inhibition of autophagy has been demonstrated to decrease chemoresistance in OS. Moreover, microRNA­22 (miR­22) inhibits autophagy, leading to an improvement in the sensitivity of cisplatin (CDDP) in OS. The aim of the present study was therefore to investigate whether miR­22 could mediate the CDDP resistance of OS cells by inhibiting autophagy via the phosphoinositide 3­kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Cell proliferation assay, LC3 flow cytometry assay and monodansylcadaverine staining in MG63 cells and CDDP resistance cells (MG63/CDDP) were performed to explore to role of miR­22 and CDDP in OS chemoresistance. Inoculation of tumor cells in an in vivo model, reverse transcription­quantitative PCR (RT­qPCR) assay, western blot analysis, and immunohistochemistry analysis were performed to investigate the role of miR­22 and CDDP in the PI3K/Akt/mTOR pathway as it is affected by autophagy. The results revealed that miR­22 inhibited the proliferation of MG63 and MG63/CDDP cells, and enhanced the anti­proliferative ability of CDDP in vivo and in vitro. miR­22 mediated the CDDP resistance of OS cells by inhibiting autophagy and decreasing CDDP­induced autophagy via downregulation of the expression of PI3K, Akt, and mTOR at the mRNA level, and the expression of PI3K, phosphorylated (p)­Akt, and p­mTOR at the protein level. It was also convincingly demonstrated that miR­22 mediates the CDDP resistance of OS by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Furthermore, in the MG63 cells that were affected by CDDP, the role of miR­22 was shown to be similar to that of the investigated inhibitor of PI3K (wortmannin) in terms of regulating the PI3K/Akt/mTOR pathway, and wortmannin could also promote the effect of miR­22. Interestingly, CDDP was demonstrated to induce autophagy by inhibiting the PI3K/Akt/mTOR pathway, whereas the pathway was upregulated in the state of chemoresistance. In conclusion, downregulation of the PI3K/Akt/mTOR pathway was shown to assist in the process of preventing chemoresistance.

Robot-assisted versus conventional laparoscopic surgery for endometrial cancer staging: A meta-analysis.

This meta-analysis broadly compared the safety and efficacy of robot-assisted laparoscopy (RAL) with that of conventional laparoscopy (CL) for endometrial cancer staging. The advantages of RAL were evaluated through the outcomes in terms of conversion rates, complications, length of operation, blood loss, number of lymph nodes harvested, and length of hospitalization. Three electronic databases (PubMed, MEDLINE, and EmBASE) were searched to identify eligible studies. We selected all retrospective studies documenting a comparison between RAL and CL for endometrial cancer staging between 2005 and 2015, and tallied with meta-analyses criteria. Only studies published in English were included in this analysis. The outcomes of the extracted data were pooled and estimated by the Review Manager version 5.1 software. Seventeen studies met the eligibility criteria. Among the 2105 patients reported, 912 underwent RAL and the other 1193 underwent CL for endometrial cancer staging. Compared with CL, RAL had lower conversion rates [risk ratio, 0.4; 95% confidence interval (CI), 0.25-0.64; p = 0.0002]. Its complications were also less than that of CL (risk ratio, 0.72; 95% CI, 0.56-0.94; p = 0.02). RAL was associated with significantly less intraoperative blood loss (weighted mean difference, -79.2 mL; 95% CI, from -103.43 to -54.97; p < 0.00001) and a shorter length of hospitalization (weighted mean difference, -0.37 days; 95% CI, from -0.57 to -0.17; p = 0.0003). We found no significant differences in the length of operation and number of lymph nodes harvested between the two groups. From our meta-analysis results, RAL is a safe and effective alternative to CL for endometrial cancer staging. Further studies are required to determine potential advantages or disadvantages of RAL.