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Inhibition of immune checkpoints is at the forefront of immunotherapy for lung cancer. However, a high percentage of lung cancer patients do not respond to these immunotherpy or their responses are transient, indicating the existence of immune resistance. Emerging evidence suggested that the interactions between cancer cells and immune system were continuous and dynamic. Here, we review how a range of cancer-cell-autonomous characteristics, tumor-microenvironment factors, and host-related influences account for heterogenous responses. Furthermore, with the identification of new targets of immunotherapy and development of immune-based combination therapy, we elucidate the methods might useful to overcome resistance.
ABSTRACT
Inhibitions of immune checkpoints, including programmed cell death 1-programmed cell death-ligand 1 (PD-1-PD-L1) axis, cytotoxic T lymphocyte associated antigen-4, are at the forefront of immunotherapy for small cell lung cancer. However, the survival benefits emerged after three to six months since therapy initiation. A growing body of evidence suggested that the current biomarkers were not consistent and convincing. Here, we review the current biomarkers including PD-L1, tumor mutation burden, DNA damage response pathway. Furthermore, we elucidate the potential biomarkers, such as tumor-infiltrating lymphocytes, circulating tumor cells. .
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Objective To investigate the role of ceramide in radiation induced bystander effect (RIBE) in vivo by irradiating Caenorhabditis elegans with proton microbeam.Methods The posterior pharynx of wide-type N2 and genetically mutated L4-staged worms was irradiated with 2 000 particles,then germ cell apoptosis and gene expression were analyzed.Results Point-fixed radiation to posterior pharynx of N2 worms significantly increased the number of apoptotic germ cells (t =9.007,P＜0.05),but not in the worms with deletion mutants of ceramide synthase (CerS) genes (hyl-1 and lagr-1) (P＞0.05).Realtime quantitative PCR assay indicated that in both N2 and lagr-1 (gk327);hyl-1 (ok976) worms,the genes of egl-1 and ced-13 in core apoptosis pathway were up-regulated after radiation to posterior pharynx,without statistical significance between these two strains (P＞0.05).The gene expression levels of hyl-1 and lagr-1 were increased in both N2 and hus-1 (op241) worms after radiation with no statistical significant difference between two strains (P＞0.05).Furthermore,radiation-induced germ cell apoptosis was increased in abl-1 (ok171) worms (t=13.241,P＜0.05),rather than in lagr-1(gk327);hyl-1(ok976);abl-1(ok171) worms (t=13.462,P＜0.05).Conclusions Ceramide is required for RIBE on germ cell apoptosis in C.elegans,and it might play function together with egl-1 and ced-13 in core apoptosis pathway and HUS-1 in DNA damage response pathway.But ceramide had antagonistic relationship with anti-apoptotic protein abl-1 in germ cell apoptosis.
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Objective To discuss the application form, method and effect of blending learning based on MOOC in Obstetrics and Gynecology Nursing Course, so as to improve learning quality and com-prehensive qualities of students. Methods Randomly selected a nursing undergraduate class as experi-mental group (n=190) and another as control group (n=189);blending learning and traditional teaching model were adopted, respectively. T test and chi-square test were used to compare scores of final exam in two groups, and Rating Scale of Self-directed Learning Competence for Nurses and Scale of Clinical Commu-nication Competence for Nursing Students were used to evaluate two groups before and after the course. Results The average score (76.30±7.08) and excellent rate (35.79％) in the experimental group were higher than those in the control group of (74.78 ±7.18) and 25.93％, with significance differences (P<0.05);Surveys showed that after the course, the autonomous learning ability and the clinical communication ability of students in the experimental group were better than before, and were better than those in the control group. Conclusion Blending learning can be applied to Obstetrics and Gynecology Nursing Course, which can effectively improve learning quality and enhance students' ability of independent study and clinical com-munication, with satisfactory teaching effects to both teachers and students.
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Objective To evaluate effect of continuous pelvic floor muscle training(PFMT) during pregnancy on delivery outcome, and to provide reference for clinical nursing work. Methods By searching database, the literature about continuous PFMT during pregnancy on delivery outcome were included,then EndNote was used to check the literature and RevMan5.2 was applied for Meta-analysis of the literature which met the inclusion criteria. Results A total of 11 papers were included. Meta-analysis showed that continuous PFMT during pregnancy can reduce lateral perineal resection rate (OR=0.66, 95%CI 0.48-0.89), increase rate of natural childbirth (OR=1.70, 95%CI 1.32-2.19) and promote progress of the first (MD=-0.52, 95%CI-0.92--0.12) and second (MD=-0.18, 95%CI-0.30--0.06) stage of labor. The intervention group shortened the first and the second stage of labor for 0.18h and 0.52h compared with the control group respectively. Conclusions Continuous PFMT during pregnancy can improve natural delivery rate, reduce the incidence of perineal side incision and shorten the time of labor, it is worthy of being promoted in clinical practice.
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BACKGROUND: Peripheral facial paralysis is treated at present only with traditional traumatic methods, such as acupuncture, moxibustion,needling with physical therapy, point-injection, thread burial therapy,scraping therapy, etc. Those methods do not act directly on the lesion of facial nerve and they are long in duration of treatment and low in curative rate. The constant magnetic aerobic atruamatic method along meridian just makes up the shortcoming of the traditional therapies.OBJECTIVE: To observe the therapeutic effects of constant magnetic aerobic atruamatic method along meridian on treatment of peripheral facial paralysis.DESIGN: Case analysis.SETTING: Department of Facial Paralysis, College of Stomatology, Fourth Military Medical University of Chinese PLA.PARTICIPANTS: Totally 1 500 cases of first diagnosed peripheral facial paralysis were employrd in 18 provinces and autonomic regions in China from June 1998 to June 2004, of which, 935 cases were male and 565 cases female. Of 103 cases were aged varied from 1.5 to 19 years, 1 105 cases from 20 to 50 years and 292 cases from 51 to 74 years. Of 672 cases were left palsy and 828 cases were right palsy. The duration of sickness was varied from 1 day to 40 years.METHODS: Constant magnetic aerobic therapy for 20 minutes was applied on facial-palsy effective points for all of cases [No.1 point: in the depression inferior to mastoid process behind ear lobe on the affected side,corresponding to the mastoid foramen, from which, the facial nerve emerges. No.2 point: on the arch top of mastoid process behind ear lobe on the affected side. No.3 point: about 3.33 cm (1 cun) above No.1 point. No.4: in the conjunction between the point about 0.5 cm posterior to the external auricular tract and the one 0.5 cm inferior to helix cms. No.5 point:about 1 cun anterior to ear apex. No.6 point: on the top of the upper border of helix on the affected side] and supplementary points [Qianzheng (Extra),Dicong (ST 4), bilateral Hegu (LI 4)], once per day, 10 days makes one course. There were a couple of days at interval between two courses, totally two courses were required. Point and oxygen therapies were applied simultaneously. Oxygen therapy: 20 minute/time, once per day, 10 days made one course, at the volume of oxygen 2-4 L/minute. Evaluation of therapeutic effects: It was to compare the changes between the affected side and healthy side in forehand wrinkles, frowning, closing eyes, whistling, blowing and smiling and the changes between two sides in nasal labial groove and philtrum during showing the teeth and at static state. Comparison of bilateral muscularis function of healthy people and patients were obtained with the six-point and four-line measurement.MAIN OUTCOME MEASURES: Results of evaluation on clinical therapeutic effects.RESULTS: Totally 1 500 cases of peripheral facial paralysis entered result analysis, no dropped out case. After 20 days treatment, 1 385 cases (92.33%) were recovered, 92 cases (6.13%) appeared significant effect, 22cases (1.74%) were improved and 1 case (0.07%) was no effect. The total effective rate was 99.93%.CONCLUSION: Constant magnetic field in combination with oxygen therapy is characterized as no pain, no trauma, no cross infection and no second injury of facial nerve, safe and convenient operation, short duration of treatment and high curative rate. It improves remarkably the symptoms of facial paralysis and recovers facial function.