Recently, immune checkpoint inhibitors (ICIs) therapy has become a promising therapeutic strategy with encouraging therapeutic outcomes due to their durable anti-tumor effects. Though, tumor inherent or acquired resistance to ICIs accompanied with treatment-related toxicities hamper their clinical utility. Overall, about 60–70% of patients (e.g., melanoma and lung cancer) who received ICIs show no objective response to intervention. The resistance to ICIs mainly caused by alterations in the tumor microenvironment (TME), which in turn, supports angiogenesis and also blocks immune cell antitumor activities, facilitating tumor cells' evasion from host immunosurveillance. Thereby, it has been supposed and also validated that combination therapy with ICIs and other therapeutic means, ranging from chemoradiotherapy to targeted therapies as well as cancer vaccines, can capably compromise tumor resistance to immune checkpoint blocked therapy. Herein, we have focused on the therapeutic benefits of ICIs as a groundbreaking approach in the context of tumor immunotherapy and also deliver an overview concerning the therapeutic influences of the addition of ICIs to other modalities to circumvent tumor resistance to ICIs.

In December 2019, an outbreak of the novel coronavirus pneumonia infection occurred in Wuhan City, Hubei Province, China, and it has received substantial attention globally. Few studies have investigated the psychological stress of students in Health University during the COVID-19 outbreak, and almost no work has attended to the influencing factors that may cause their psychological stress risk. This cross-sectional, surveybased, region-stratified study collected demographic data and mental measurement from 2,498 medical students and 1,177 non-medical students in 31 provinces from March 5, 2020, to March 10, 2020, in China. The psychological stress was measured using the Chinese Perceived Stress Scales (CPSS) under a self-design questionnaire. Sociodemographic, major characteristics, and knowledge of the novel coronavirus pneumonia were also identified as potential influencing factors of stress. The study revealed that medical students are suffering from more stress than non-medical students almost in all provinces of China. Four influencing factors including level of familiarity with the novel coronavirus, family income, major of students, and status of the intern student can be significantly related to students' stress in the medical group by using the univariate and multivariate analysis. Further analysis showed that students with low stress had a greater number of positive psychological emotions and a lower number of negative psychological emotions than with medical students with high stress. In addition, high stress caused low enthusiasm for learning in these medical students and lead to little/no willingness to do professional medical work in the future. In conclusion, we need to increase the level of our knowledge related to the novel coronavirus pneumonia to reduce stress and strongly focus on the special populations in medical students with certain features, such as intern students, clinical nursing students, and lowincome families, to improve their learning attitudes and establish positive professional mental outlooks.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown that miRNAs expression are changed in various diseases, such as cancers, autoimmune disease, infectious diseases, and neurodegenerative Diseases. The suppression of miRNA function can be easily attained by utilizing of anti-miRNAs. In contrast, an enhancement in miRNA function can be achieved through the utilization of modified miRNA mimetics. The discovery of appropriate miRNA carriers in the body has become an interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency and safety for transferring different cellular biological components to the recipient cell have attracted significant attention for their capability as miRNA carriers. Mesenchymal stem cells (MSCs) are recognized to generate a wide range of EXOs (MSC-EXOs), showing that MSCs may be effective for EXO generation in a clinically appropriate measure as compared to other cell origins. MSC-EXOs have been widely investigated because of their immune attributes, tumor-homing attributes, and flexible characteristics. In this article, we summarized the features of miRNAs and MSC-EXOs, including production, purification, and miRNA loading methods of MSC-EXOs, and the modification of MSC-EXOs for targeted miRNA delivery in various diseases. Graphical abstract

Background At the present time, colorectal cancer (CRC) is still known as a disease with a high mortality rate. Theranostics are flawless scenarios that link diagnosis with therapy, including precision medicine as a critical platform that relies on the development of biomarkers particularly “liquid biopsy”. Circulating tumor cells (CTCs) and tumor-derived exosomes (TDEs) in a liquid biopsy approach are of substantial importance in comparison with traditional ones, which cannot generally be performed to determine the dynamics of the tumor due to its wide restriction of range. Thus, recent attempts has shifted towards minimally noninvasive methods. Main text CTCs and TDEs, as significant signals emitted from the tumor microenvironment, which are also detectable in the blood, prove themselves to be promising novel biomarkers for cancer diagnosis, prognosis, and treatment response prediction. The therapeutic potential of them is still limited, and studies are at its infancy. One of the major challenges for the implementation of CTCs and TDEs which are new trends in translational medicine is the development of isolation and characterization; a standardizable approach. This review highlights and discusses the current challenges to find the bio fluids application in CRC early detection and clinical management. Conclusion Taken together, CTCs and TDEs as silent drivers of metastasis can serve in the management of cancer patient treatment and it is of the upmost importance to expand our insight into this subject. However, due to the limited data available from clinical trials, further validations are required before addressing their putative application in oncology.