BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods:A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results:After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased.Conclusions:Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.

Objective:To investigate the role of p21 gene in the radiation-induced heart disease (RIHD) and to evaluate the effect on p21 gene knockout on RIHD phenotype in mouse models.Methods:p21 -/-mice were utilized in the experimental group, and p21 + /-mice were allocated in the control group. RIHD mouse models were established by exposure to 10 Gy whole heart irradiation by using a small animal radiation research platform. The heart samples were collected at 6 weeks after irradiation, the gross specimens were measured and subject to HE staining. The wall thickness and left ventricular ejection fraction of the mice were detected by the Vevo2100 ultrasound imaging system. The hypoxia in cardiac tissues was detected by the hypoxia probe method. The apoptosis of cardiac cells was determined by Tunel method. Results:Compared with the p21 + /-mice, the survival of p21 -/-mice was significantly shortened ( P=0.004), the interventricular septum was significantly thinned during the diastolic and systolic phases ( P=0.049, P=0.006), the left ventricular posterior wall was remarkably thickened ( P<0.001) and the left ventricular ejection fraction was significantly decreased ( P=0.004). The gross heart tissue was enlarged in the p21 -/-mice. HE staining showed the aggregation of inflammatory cells in cardiac tissues and disordered arrangement of myocardial cells. Significant hypoxia and apoptosis could be observed in the p21 -/-mouse heart tissues. Conclusions:p21 -/-mice are prone to more severe RIHD after irradiation, manifested with shortened cardiac survival, weakened cardiac function, abnormal cardiac structure, hypoxia and apoptosis of cardiac tissues. p21 plays an important role in the repair after cardiac irradiation.

Immune checkpoint inhibitors (ICIs) is a negative regulatory factor antibody, which activates T cells to play an anti-tumor effect in immunotherapy, and can also cause immune-related adverse responses, thereby inducing a series of immune related adverse events (irAEs). Among these irAEs, although the incidence of ICIs-related myocarditis is very low, the fatality rate is significantly higher than other adverse reactions, close to 50%. Clinicians should be vigilant when applying ICIs, but the pathogenesis of ICIs-related myocarditis is still unclear. This article combines the recent research results of ICIs to summarize the mechanism and clinical manifestations of ICIs-related myocarditis, so as to improve clinicians' understanding of the adverse reactions.
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Biomedical Research/trends* ; Cardiotoxicity/physiopathology* ; Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy/adverse effects* ; Myocarditis/physiopathology* ; Neoplasms/drug therapy*

Leptomeningeal metastasis (LM) is one of the serious complications of advanced non-small cell lung cancer (NSCLC), although the incidence is not high, the clinical symptoms are severe and the prognosis is poor. LM is prone to occur in patients with positive driver gene than negative. At present, the treatment of LM mainly includes molecular targeted therapy, systemic chemotherapy, whole brain radiotherapy, intrathecal chemotherapy and immunotherapy. Although there are many treatments, the efficacy of LM is still unsatisfactory. This article reviews the drug therapy of sensitive driver gene positive NSCLC LM.

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.

AIM:To investigate whether specific small interfering RNA ( siRNA) targeting Toll-like receptor 4 ( TLR4) gene inhibits the proliferation of cervical cancer cell line HeLa through NF-κB signaling pathway and down-regula-tion of Bcl-2 expression.METHODS:Three specific TLR4 siRNAs and 1 negative siRNA were transfected respectively in-to HeLa cells.The expression of TLR4 at mRNA and protein levels was measured by reverse transcription-polymerase chain reaction ( RT-PCR) and Western blotting , respectively .The protein expression of p 65 and Bcl-2 was detected by Western blotting.The cell proliferation was determined by MTT assay and plate colony formation assay .The apoptotic rate of the cells and the cell cycle were analyzed by flow cytometry .RESULTS:In comparison with the other 2 kinds of TLR4 siR-NAs, TLR4-siRNA-003 demonstrated the strongest silencing effect on TLR4 gene expression in the HeLa cells at 48 h after transfection.The expression of TLR4 at mRNA and protein levels was reduced by 62% and 89%, respectively.The pro-tein levels of p65 and Bcl-2 significantly decreased .The growth rate of HeLa cells transfected with TLR 4-siRNA-003 was significantly inhibited .Moreover , the cell apoptotic rate increased significantly and the cell cycle was arrested at G 1 phase as the HeLa cells were transfected with TLR 4-siRNA-003 for 48 h.CONCLUSION:Specific TLR4 siRNA effectively in-hibits the expression of TLR4 and inhibits the proliferation of cervical cancer HeLa cells through NF-κB signaling pathway and down-regulation of Bcl-2 expression, indicating that TLR4 may be a new target for the treatment of cervical cancer .

Objective To investigate and design a coincidence detection system for an all-digital small animal PET scanner and evaluate its preliminary performance properties.Methods This coincidence module adopted a coincidence identification mode based on singles data in list-mode.Using digital signal processing technology,energy calibration,crystal identification,timing alignment and coincidence events extraction were performed on singles data in list-mode.The obtained data could be used for image reconstruction.Results The 13 × 13 crystal array was well recognized by the position histogram of one lutetium yttrium orthosilicate (LYSO) crystal block.In the coincidence timing histogram of the micro-Derenzo phantom,1.36 ns full width at half maximum was obtained.The rods with a diameter of 1.2 mm were clearly displayed in the reconstructed image of the micro-Derenzo phantom.Conclusion The coincidence module can provide satisfactory performance to meet the design needs of an all-digital small animal PET scanner.

Objective: To evaluate the therapeutic effects of Rituximab combined with CHOP on B cell non-Hodgkin's lymphoma. Methods: A prospective study with concurrent control group was carried out. A total of 60 cases of B cell non-Hodgkin's lympoma were divided into 2 groups. The 30 cases in the research group received Rituximab combined with CHOP regimen. The 30 cases in the control group were treated with CHOP regimen alone. CHOP regimen (Cyclophospham 600mg/m~2 IV, Vincristine 1.4mg/m~2 Ⅳ, and Adriamy-cin piarubicin 50mg/m~2 IV) was administered on the first day of chemotherapy course. Prednisone 100mg/m~2 was administered orally from the first day to the fifth day. The cycle was repeated every 21 days and the patients received at least 3-6 cycles of chemotherapy. The therapeutic effect was assessed. Results: The complete remission (CR) rate and total response rate were 66.7% (20/30) and 90.0% (27/30) in the research group and 39.97% (12/30) and 56.7% (17/30) in the control group. The therapeutic differences between the two groups showed a statistical significance (P＜0.05). Conclusion: Compared with CHOP regimen chemotherapy, Rituximab combined with CHOP regimen shows better therapeutic effect. The side effects in the research group are similar to those in the control group. Rituximab combined with CHOP regimen can be the first choice in the treatment for B cell non-Hodgkin's lymphoma.

To evaluate the effect of mobilization of peripheral blood stem cells (PBSC) with high dose cyclophosphamide combination chemotherapy and G-CSF in breast cancer patients, a new mobilization protocol was designed on the basis of standard combination chemotherapy regimen, in which the dose of cyclophosphamide was raised to 2 to 4 times, and G-CSF began to be used at the dose of 150 micro g twice everyday when white blood cell (WBC) decreased below 1.0 x 10(9)/L. PBSC collection was performed while WBC increased over 5.0 x 10(9)/L during bone marrow recovering. The PBSC mobilization protocol was completed in 10 patients, the median nadir of WBC was 0.8 (0.4 - 1.0) x 10(9)/L, the median time of PBSC collection was 2 (2 - 4), the median number of collected CD34(+) cells was 6.43 (1.99 - 8.75) x 10(6)/kg. The results showed that the protocol, high dose cyclophosphamide combination chemotherapy, was an optimal PBSC mobilization regimen in breast cancer patients.