Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Combination of Radiation Therapy and Immunotherapy for Non-small Cell Lung Cancer: Peer Exchange on Frontier Academic Topics / 中国肺癌杂志

Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.

Management strategy for adverse events of immune checkpoint inhibitors / 中国肿瘤临床

Currently, immune checkpoint inhibitors (ICPIs) are the most compelling approach in cancer therapy, which expanded the boundary of treatment of cancer to immune-based therapy. Compared to traditional chemotherapy, immunotherapy significantly pro-longs survival while conferring fewer side effects. Because of the new mechanism of the ICPIs with good clinical efficacy, they have been approved for sale in a short time. However, the mechanism of immune-related adverse events have yet fully understood for a standardized management strategy. With further development of immunotherapy and possible combination therapy, adverse events of ICPIs gain more attention. Here, we focuses on the reported adverse events and the treatment experience to provide theoretical ba-sis for their treatment.

Effect of Chinese Materia Medica with Tonifying Kidney Function on Transplantation of Multipotency Mesenchymal Stem Cells from Human Umbilical Cord in Mice Model of Acute Kidney Injury / 中草药·英文版

Objective: Mesenchymal stem cells (MSCs) represent a promising population for supporting new clinical concepts in cellular therapy, and they can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. Methods: This method opened up a new era of stem cell research, because the transplantation rejection of iPSCs is the bottleneck of its clinical application, so seeking alternative compounds and animal origin diagnostic reagents to achieve full chemical iPSCs is to be done to solve this problem. Results: The application of these iPSCs has largely been associated with well known undesirable effects such as the development of cancers in certain experimental models. This has called for the search and use of reprogramming factors that are safe. Chinese materia medica (CMM) with tonifying kidney function (TKF) offers an alternative source. On the other hand, human umbilical cord mesenchymal stem cells (hUMSCs) are known to be a "young" source of MSCs, hUMSCs transplantation is an attractive approach for acute kidney injury repair. Therefore, In this study, we investigated whether the treatment of CMM with TKF on hUMSCs could enhance the repair in mice model of acute kidney injury after transplantation. Conclusion: Our results showed that the treatment of hUMSCs with kidney tonifying CMM increased their multipotency, improved the renal function of mice and enhanced subsequent homing to the injured kidney in an acute kidney injury mice model.

Genetic Polymorphism Analysis of Drug-metabolizing Enzyme CYP2C19*2 in Tumor Patients of Han Poputation from Hubei Province / 医药导报

Objective To investigate the distribution frequency of allele genetic polymorphism of drug-metabolizing enzyme CYP2C19?2 (rs4244285) in tumor patients of Han population from Hubei province,to provide guidance for clinical rational drug use related to the genetic polymorphism. Methods CYP2C19?2 genotyping was performed by Fluorescence Dye Terminator Cycle Sequencing System in 285 cancer patients. Genotype frequency and allele frequency were calculated and the genotype distribution in different genders was compared. Compared with the previous studies, we clarified the frequencies of CYP2C19?2 gene polymorphisms in different nationalities. Results All the 285 patients in this study were Han population. The genotype frequency of CYP2C19?2 was 113 (39.6%),138 (48.4%) and 34 (11.9%) for wild-type homozygote (GG), heterozygote (GA) and variant homozygote (AA),respectively.The CYP2C19?2 mutant allele frequency was 36.1%.Genotype distribution of male and female patients did not reach significant difference. Conclusion There is no difference in CYP2C19?2 genotypes distribution among different ethnic groups.

Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients / 华中科技大学学报（医学）（英德文版）

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1 / 华中科技大学学报（医学）（英德文版）

miR-200c has been shown to regulate the epithelial-mesenchymal transition (EMT) by inhibiting ZEB1 and ZEB2 expression in breast cancer cells. This study further examined the role of miR-200c in the invasion and metastasis of breast cancer that goes beyond the regulation on ZEB1 and ZEB2 expression. In this study, the bioinformatics software (miRanda) was used to predict the target gene of miR-200c and Renilla luciferase assay to verify the result. The metastatic breast cancer cells MDA-MB-231 were cultured and transfected with the miR-200c mimic or inhibitor. The expressions of miR-200c and HMGB1 were detected by RT-PCR and Western blotting, respectively. Transwell assay and wound healing assay were employed to examine the invasive and migrating ability of transfected cells. Target prediction and Renilla luciferase analysis revealed that HMGB1 was a putative target gene of miR-200c. After transfection of MDA-MB-231 cells with the miR-200c mimic or inhibitor, the expression of miR-200c was significantly increased or decreased when compared with cells transfected with the miR-200c mimic NC or inhibitor NC. Moreover, the expression of HMGB1 was reversely correlated with that of miR-200c in transfected cells. Tranwell assay showed that the number of invasive cells was significantly reduced in miR-200c mimic group when compared with miR-200c inhibitor group. It was also found that the migrating ability of cells transfected with miR-200c mimics was much lower than that of cells transfected with miR-200c inhibitors. It was suggested that miR-200c can suppress the invasion and migration of breast cancer cells by regulating the expression of HMGB1. miR-200c and HMGB1 may become useful biomarkers for progression of breast cancer and targets of gene therapy.

Effect of Everolimus on Radiosensitivity of Human Non_small Cell Lung Cancer Cell Line A549 / 医药导报

Objective To exPlore the effect of mammalian target of raPamycin ( mTOR ) inhibitor eVerolimus on radiosensitiVity of human non_small cell lung cancer cell line in vitro by using eVerolimus to inhibit mTOR signaling Pathway of A549. Methods Human non_small cell lung cancer cell line A549 was subjected to radiation alone or in combination with eVerolimus treatment. The 50%inhibition concentration ( IC50 ) of eVerolimus in A549 cells was detected by methylthiazol tetrazolium ( MTT) assay in vitro. EVerolimus at the 20%inhibition concentration ( IC20 ) was used to Pretreat A549 cells for 24 h. Cells were then irradiated by X_ray with 2,4,6,8 Gy. The cell surViVal fraction was comPuted by clone formation. Cell surViVal curVe was fitted by multitarget one_hit model, and mean lethal dose ( D0 ), dose quasithreshold ( Dq ), surViVal fraction at 2 Gy ( SF2 ), and sensitization enhancement ratio (SER) were calculated. The exPression ofγ_H2AX was determined by Western blotting and then the relatiVe gray Values were analyzed. Results EVerolimus significantly imProVed the sensitiVity of A549 cells to radiation. The D0 , Dq and SF2 of eVerolimus+irradiation grouP were significantly lower than those of irradiation grouP. The SER was 1. 36. The residual amount of γ_H2AX Protein in the eVerolimus + irradiation grouP was significantly higher than that of the irradiation grouP. Conclusion EVerolimus inhibiting mTOR signaling Pathway can increase the radiosensitiVity of A549 cells.

miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1 / 华中科技大学学报（医学）（英德文版）

miR-200c has been shown to regulate the epithelial-mesenchymal transition (EMT) by inhibiting ZEB1 and ZEB2 expression in breast cancer cells. This study further examined the role of miR-200c in the invasion and metastasis of breast cancer that goes beyond the regulation on ZEB1 and ZEB2 expression. In this study, the bioinformatics software (miRanda) was used to predict the target gene of miR-200c and Renilla luciferase assay to verify the result. The metastatic breast cancer cells MDA-MB-231 were cultured and transfected with the miR-200c mimic or inhibitor. The expressions of miR-200c and HMGB1 were detected by RT-PCR and Western blotting, respectively. Transwell assay and wound healing assay were employed to examine the invasive and migrating ability of transfected cells. Target prediction and Renilla luciferase analysis revealed that HMGB1 was a putative target gene of miR-200c. After transfection of MDA-MB-231 cells with the miR-200c mimic or inhibitor, the expression of miR-200c was significantly increased or decreased when compared with cells transfected with the miR-200c mimic NC or inhibitor NC. Moreover, the expression of HMGB1 was reversely correlated with that of miR-200c in transfected cells. Tranwell assay showed that the number of invasive cells was significantly reduced in miR-200c mimic group when compared with miR-200c inhibitor group. It was also found that the migrating ability of cells transfected with miR-200c mimics was much lower than that of cells transfected with miR-200c inhibitors. It was suggested that miR-200c can suppress the invasion and migration of breast cancer cells by regulating the expression of HMGB1. miR-200c and HMGB1 may become useful biomarkers for progression of breast cancer and targets of gene therapy.

The explore of curriculum integration during Eight-year-term medical education / 中华医学教育探索杂志

Objective To research the affection and problem of Curriculum integration teaching method in eight-year term Medical Education.Methods Combination teaching and tradition teaching methods were employed in 100 students (Eight-year-term) and 127 students (Seven-year-term) respectively.A questionnaire survey and teaching effect were analyzed at last (employx2 analysis).Results Currculum integration is more acceptable(x2 =3.92,P ＜ 0.05),effective (x2 =11.07,P ＜0.01 ),systematic (x2 =11.82,P ＜ 0.01 ) and improve self-study ability better(x2 =8.51,P ＜ 0.01 ).But it's not helpful for the study enthusiasm(x2 =0.90,P ＞0.05).Conclusion Combination teaching method is more acceptable and effective than tradition method.However,the enthusiasm of study is not improved obviously.Combination Curriculum integration teaching method is a good one and worth popularizing.

Resilience in China recruits and its influencing factors / 中华行为医学与脑科学杂志

Objective To explore the characteristic and its influencing factors of resilience in Chinese recruits to provide the scientific evidence for the mental health training. Methods Resilience Scale for Adults (RSA) ,Self-report Symptom Checklist 90( SCL-90), Eysenck Personality Questionnaire(EPQ) and General SelfEfficacy Scale (GSES) were applied to 2459 recruits(2231 males and 139 females, aged ( 19 ± 1.5 ) ) within two male recruits( 101.76 ± 14.06) was significantly higher than that of males (96.65 ± 15.62) ( t=4. 13, P＜0. 0l ) ;Recruits with College and above education have significantly higher RSA scores than those with junior high school education and senior high school education (P ＜ 0. 0l ). Between the only child group and non only child group, there was no significant difference in RSA total score , but significant difference existed only in three factors higher RSA group scored significantly higher in extraversion (Z = 19.13, P = 0.000), abreaction adjustment (Z =8.67, P = 0.600 ) and self-efficacy (Z = 19.48, P = 0.000 ), while scored significantly lower in the SCL-90 (Z =Resilience had significant positive correlation with extraversion, abreaction adjustment and self-efficacy, and negative correlation with the neuroticism and inhibition adjustment. Multiple linear regression analysis revealed that extraversion, neuroticism,abreaction adjustment/inhibition adjustment and self-efficacy had predictive ability to resilience( explain 41% ). Conclusion Chinese recruits have good resilience. Emotion Regulation (abreaction adjustment/inhibition adjustment), extraversion, neuroticism and self-efficacy are important influencing factors of resilience for Chinese recruits.

Evaluation of whole body MRI and diffusion-weighted MRI in detecting intranodal lesions in patients with lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the whole body MRI and diffusion-weighted MRI in detecting intranodal lesions in patients with lymphoma.</p><p><b>METHODS</b>Whole body MRI and diffusion-weighted MRI (DWI) were performed in 23 patients with histologically proven lymphoma. A conventional coronal MRI scan from head to inguinal groove was done for whole body scanning. In the DWI, axial MRI scans were performed after segmentation based on SENSE technique, and all images were merged into whole body image reconstruction by software.</p><p><b>RESULTS</b>417 lymph nodes were detected by MRI in the 23 patients. The overall positive rate of whole body MRI and DWI was 79.1% and 89.7%, respectively. It was 70.9% versus 85.2% and 79.4% versus 90.1% for the lymph nodes of < 2 cm and 2-3 cm in diameter, with a significant difference between the two methods (P < 0.01). However, it was 94.7% versus 97.9% for the lymph nodes of > 3 cm in diameter, not significantly different between the two methods (P > 0.05). Both methods had similar sensitivity in detecting the lymph nodes in the neck, supraclavicular and infraclavicular fossae, mediastinum and axillary fossa. However, the positive rate of whole body MRI was 51.2%, 43.8% and 52.2%, significantly less sensitive than 83.7%, 71.9% and 87.0%, respectively, by DWI in detecting the lymph nodes in the retroperitoneal space, pelvic cavity and inguinal groove (all P < 0.01).</p><p><b>CONCLUSION</b>Both whole body MRI and diffusion-weighted MRI have a relative high sensitivity in detecting intranodal lesions for patients with lymphoma, showing a certain value in clinical application.</p>

Mechanism of differentiation of mesenchymal stem cells into neuron-like cells in vitro / 中国康复理论与实践

@#ObjectiveTo study the mechanism of differentiation of mesenchymal stem cells(MSCs) into neuron-like cells in vitro.MethodsMSCs of Wistar rats were separated and cultured, and then induced with DMSO and BHA in vitro. The specific marking proteins of neurons, glia and neural stem cells were detected before preinduction, at 24h after preinduction, at 6h, 24h, and 48h after neuronal induction.ResultsAfter the inducement, many MSCs turned into bipolar,multipolar and taper,and then intersected as network structure. Nestin was strong positive at 6h after neuronal induction, and decreased at 24h, 48h after the induction. NeuN was present at 6 h after neuronal induction, and increased at 24h, 48h after the induction.ConclusionMSCs can be induced into neural stem cells(NSCs) at first, and then differentiate into neuron-like cells in vitro.

Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells / 华中科技大学学报（医学）（英德文版）

In order to study whether marrow stromal cells (MSCs) can be induced into nerve-like cells in vitro, and the mechanism, the MSCs in Wistar rats were isolated and cultured, and then induced with DMSO and BHA in vitro. The expression of specific marking proteins in neurons, glia and neural stem cells were detected before preinduction, at 24 h of preinduction, at 6 h, 24 h, and 48 h of neuronal induction by using immunohistochemistry and Western blotting. The ultrastructural changes after the inducement were observed. The results showed that after the inducement, many MSCs turned into bipolar, multipolar and taper, and then intersected as network structure. At the same time, some MSCs had the typical neuron-like ultrastructure. Immunohistochemistry revealed that NeuN and Nestin expression was detectable after inducement, but there was no GFAP and CNP expression. Western blotting showed the expression of Nestin was strong at 6 h of neuronal induction, and decreased at 24 h, 48 h of the induction. NeuN was detectable at 6 h of neuronal induction, and increased at 24 h, 48 h of the induction. It was concluded MSCs were induced into neural stem cells, and then differentiated into neuron-like cells in vitro.

Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells / 华中科技大学学报（医学）（英德文版）

In order to study whether marrow stromal cells (MSCs) can be induced into nerve-like cells in vitro, and the mechanism, the MSCs in Wistar rats were isolated and cultured, and then induced with DMSO and BHA in vitro. The expression of specific marking proteins in neurons, glia and neural stem cells were detected before preinduction, at 24 h of preinduction, at 6 h, 24 h, and 48 h of neuronal induction by using immunohistochemistry and Western blotting. The ultrastructural changes after the inducement were observed. The results showed that after the inducement, many MSCs turned into bipolar, multipolar and taper, and then intersected as network structure. At the same time, some MSCs had the typical neuron-like ultrastructure. Immunohistochemistry revealed that NeuN and Nestin expression was detectable after inducement, but there was no GFAP and CNP expression. Western blotting showed the expression of Nestin was strong at 6 h of neuronal induction, and decreased at 24 h, 48 h of the induction. NeuN was detectable at 6 h of neuronal induction, and increased at 24 h, 48 h of the induction. It was concluded MSCs were induced into neural stem cells, and then differentiated into neuron-like cells in vitro.