Further understanding of an uncommon disease of combined small cell lung cancer： clinical features and prognostic factors of 114 cases

Objective： Combined small cell lung cancer （C-SCLC） is an uncommon subgroup of small cell lung cancer （SCLC） and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods： Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results： One hundred and fourteen patients were enrolled, with a median age of 59 （range： 20-79） years old. The most common combined component was squamous cell carcinoma （52.6%）. Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients （70.2%） received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival （OS） was 26.2 months. On univariate analysis, smoking （P=0.029）, Karnofsky performance score （KPS） 〈80 （P=0.000）, advanced TNM stage （P=0.000）, no surgery （P=0.010）, positive resection margin （P=0.000）, positive lymph nodes ≥4 （P=0.000）, positive lymph node ratio 〉10% （P=0.000） and non-multimodality treatment （P=0.004） were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions： C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.

Improving cancer therapy by combining cell biological, physical, and molecular targeting strategies

Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.

ASFV pp62 Protein Has 9 Dominant B-T Cell Combined Epitopes

[Objective]The paper was to study the basic characteristics of the pp62 protein of the African swine fever virus strain Pig/HLJ/2018,and to provide more basic data for the study of the virus.[Method]We used the ProtParam program to analyze the physical and chemical properties of the pp62 protein.TMHMM-2.0 and SignalP-5.0 were used to analyze protein transmembrane region and signal peptide,and Lasergene 7.0 Protean program was used to study protein antigen index,hydrophilicity,surface accessibility and titration curve.Protein N-glycosylation site and O-glycosylation site came out with NetNGlyc-1.0 and NetOGlyc-4.0 online servers.Then,PSIPRED-4.0,NetSurfP-2.0,and PSRSM were used to analyze protein secondary structure,BepiPred1.0 and IEDB tools were used to analyze protein B-cell epitopes,and NetMHC 4.0 and NetMHCpan tools were used to analyze protein T-cell epitopes.And we used Swiss-Model to analyze the high-level structure of the protein,the EzMol tool to visually analyze B-T cell combined epitopes,and finally,MEGA 7.0 to analyze the genetic evolutionary relationship of the protein.[Result]The pp62 protein of African swine fever viral strain Pig/HLJ/2018 had a molecular weight of 60.5 kDa.It was a hydrophilic acid labile protein,and had no transmembrane region and signal peptide.There were 5 N-glycosylation sites and 4 O-glycosylation sites.Analysis of the secondary structure of the protein showed that the proportions of helix,coil and strands were 45.5%,41.7%and 12.8%,respectively.The study of dominant epitopes revealed that there were 14 dominant B-cell epitopes and 16 dominant T-cell epitopes.And 9 dominant B-T cell combined epitopes located on the surface of the protein molecule were found.The phylogenetic tree constructed with the pp62 protein showed that the evolutionary relationship of Pig/HLJ/2018 strain was the closest to Georgia/2007/1,which belonged to genotype II.[Conclusion]The results will provide basic information for pp62 research.

Envafolimab combined with chemotherapy in the treatment of combined small cell lung cancer: A case report

BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.

Combination of tumor-associated regulatory T cell deletion and PD-1/PD-L1 blockade: A promising immunotherapy for hepatocellular carcinoma?

During the past decades,the treatment of hepatocellular carcinoma(HCC)has been limited to surgical resection and liver transplantation,but the prognosis is still poor.Recently,tumor immunotherapy,particularly immune checkpoints programmed cell death-1/programmed cell death ligand-1(PD-1/PD-L1)blockade,brings a breakthrough for HCC[1,2].However,anti-PD-1/PD-L1 immunotherapy is not satisfactory and the response rates were between 20%and 30%[3].How to improve the efficacy of PD-1/PD-L1blockade is the main issue.

Monitoring the changes in plasm C-reactive protein,fibrinogen and blood white cell in patients with primary hypertension combined with acute cerebral infarction

BACKGROUND： Inflammatory reaction and the increased level of its accompanying active protein play an important role in the occurrence and development of cerebral infarction. C-reactive protein, fibrinogen and white blood cell, as the monitoring index of inflammatory reaction, are very important in the occurrence and development of acute cerebral infarction. OBJECTIVE： To make a comparison between patients with primary hypertension accompanied with acute cerebral infarction and with simple primary hypertension by observing the changes in plasma C-reactive protein and fibrinogen levels as well as white blood cell and differential counts and analyzing their significances. DESIGN ： Controlled observation SETTING ： Ward Building for VIP, Shenzhen Hospital, Peking University. PARTICIPANTS： Totally 133 patients with primary hypertension were selected from Ward Building for VIP, Shenzhen Hospital, Peking University during September 2003 to September 2005, The diagnostic criteria were based on the hypertension diagnosis criteria formulated by the 7^th World Health Organization-International Society of Hypertension Guidelines （WHO-ISH） in 1998. The informed consents were obtained from all the participants. The involved patients were assigned into two groups： primary hypertension group, in which, there were 65 patients with primary hypertension （ degree 2）, including 42 males and 23 females, with mean age of （61 ±14）years and mean blood pressure of （162.7±6.8）/（94.2±8.4） mm Hg （1 mm Hg =0.133 kPa）, and primary hypertension combined with cerebral infarction group, in which, there were 68 patients with primary hypertension combined with cerebral infarction （ meeting the diagnostic criteria formulated in the 4^th National Cerebrovascular Diseases Meeting in 1995 and diagnosed by skull CT or MRI to exclude the patients with lacunar infarction）, including 42 males and 26 females, with mean age of （56±15） years and mean blood pressure of （176.4±9.2）/（96.3±9.7） mm Hg. METHODS： Plasm C-reactive protein and fibrinogen levels, and white blood cell and differential counts of patients in the two groups were examined 24 hours after stroke. The above indexes were re-examined in the primary hypertension combined with cerebral infarction group 72 hours after stroke. White blood cell and differential counts were performed with laser method （East Asia FE-95001 RAM-1, Japan）. The level of C-reactive protein was measured with turbidimetry （BNII Automatic Systems For Analysis, USA）. The level of fibrinogen was measured with algorithm method when prothrombin time was normal and with Clauss method when prothrombin time was abnormal （ACL Automatic Coagulation Analyzer, USA）. MAIN OUTCOME MEASURES： The plasm C-reactive protein and flbrinogen levels, and white blood cell and differential counts 24 hours after stroke in two groups and 72 hours after stroke in primary hypertension combined with cerebral infarction group. RESULTS： All the 133 involved patients participated in the result analysis. The plasm C-reactive protein and fibrinogen levels, and white blood cell and neutrophil counts in patients with primary hypertension were all within the normal range. The plasm C-reactive protein and fibrinogen levels, and white blood cell and neu- trophil counts in patients with primary hypertension combined with cerebral infarction were significantly higher than those in patients with primary hypertension 24 hours after stroke and 72 hours after stroke respectively[24 hours after stroke：（32.12±11.76） mg/L vs. （5.02±3.21 ） mg/L;（4.64±0.75） g/L vs. （3.12±0.49） g/L; （9.32±81）×10^9 L^- 1 vs. （5.78±1.32）×10^9L^- 1 （7.85±2.38）×10^9 L^- 1 vs.（3.49±1.28）×10^9 L^-1,t =7.094, 5.759,4.106,5.491, respectively,all P〈 0.01; 72 hours after stroke： （47.62±18.43） mg/L vs. （32.12±11.76） mg/L; （5.08±0.82） g/L vs. （4.64±0.75） g/L, t =2.864,2.220, respectively, both P 〈 0.05]. CONCLUSION： The increase in fibrinogen level and white blood cell count are the important index in monitoring primary hypertension combined with acute cerebral infarction. The increase in plasm C-reactive protein and fibrinogen levels 72 hours after stroke indicates that plasma C-reactive protein and fibrinogen are very important in the development of disease.

Com bined effect of alphafetoprotein antisense oligodeoxynucleotidesand 5-fluorouracil on human hepato ma cell growth

Objective To investigate the effect of alpha fetoprotein (AFP) antisense phosphorothioate oligodeoxynucleotides in combination with 5 fluorouracil (5 FU) on the growth of BEL 7404 human hepatoma cells in vitro Methods Phosphorothioate oligodeoxynucleotides were synthesized by β cyanoethyl phosphoramidite chemistry AFP gene expression in human hepatoma cells was determined by avidin biotin peroxidase complex (ABC) immunocytochemical method Cell growth in the presence or absence of experimental agents was measured using 3 (4, 5 dimethylthiazol 2 yl) 2, 5 dipheny ltetrazolium (MTT) microculture tetrazolium assay Results AFP antisense oligomers markedly suppressed the growth of BEL 7404 human hepatoma cells in vitro by sequence specific blocking of the AFP gene expression in the cells (P<0 05) 5 FU also inhibited the hepatoma cell growth in a dose dependent manner when used alone (P<0 05) The combined treatment with AFP antisense oligomers and 5 FU showed significantly enhanced hepatoma cell growth inhibition than either AFP antisense or 5 FU treated cells alone (P<0 05) Conclusion Combined use of AFP antisense oligomers and 5 FU could more effectively inhibit the growth of BEL 7404 human hepatoma cells in vitro

Spotlight on chimeric antigen receptor engineered T cell research and clinical trials in China

T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for decades. Recently, the biosynthetic chimeric antigen receptor engineered T cell(CAR-T) strategy was developed and exhibited encouraging clinical efficacy, especially in hematological malignancies. Chimeric antigen receptor research reports began in 2009 in China according to our Pub Med search results. Clinical trials have been ongoing in China since 2013 according to the trial registrations on clinicaltrials.gov.. After years of assiduous efforts, research and clinical scientists in China have made their own achievements in the CAR-T therapy field. In this review, we aim to highlight CAR-T research and clinical trials in China, to provide an informative reference for colleagues in the field.

ADVANCE NON SMALL CELL LUNG CANCER ACCEPTING CHEMOTHERAPY COMBINED WITH SHENMAI INJECTION

The aim of the study was to observe the changes of vascular endothelial growth factor(VEGF)and the efficacy of patients with advanced non-small-cell lung cancer(NSCLC)after the treatment of chemotherapy with Shenmai Injection.This study is a randomized controlled,prospective,single blind trial.63 eligible patients with NSCLC were

Effect of Fuzheng Kang'ai recipe combined with gefitinib on lung cancer A549 cells and its mechanism research

Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with

Value assessment of hydrogen-based electrical energy storage in view of electricity spot market

Hydrogen as an energy carrier represents one of the most promising carbon-free energy solutions.The ongoing development of power-to-gas(Pt G)technologies that supports large-scale utilization of hydrogen is therefore expected to support hydrogen economy with a final breakthrough.In this paper,the economic performance of a MW-sized hydrogen system,i.e.a composition of water electrolysis,hydrogen storage,and fuel cell combined heat and power plant(FCCHP),is assessed as an example of hydrogen-based bidirectional electrical energy storage(EES).The analysis is conducted in view of the Danish electricity spot market that has high price volatility due to its high share of wind power.An economic dispatch model is developed as a mixed-integer programming(MIP)problem to support the estimation of variable cost of such a system taking into account a good granularity of the technical details.Based on a projected technology improvement by 2020,sensitivity analysis is conducted to illustrate how much the hydrogen-based EES is sensitive to variations of the hydrogen price and the capacity of hydrogen storage.