Pulmonary blastoma treatment response to anti-PD-1 therapy: a rare case report and literature review.

Pulmonary blastoma (PB) is a rare and invasive malignancy of the lungs with a poor prognosis. Although the mainstay treatment of PB is surgery, and radiotherapy and chemotherapy have been reported, no standard therapy exists for patients inoperable in advanced stages. Moreover, little is known about driver mutation status and immunotherapy efficacy. This paper presents a male patient diagnosed with classic biphasic PB using CT-guided lung biopsy pathology and immunohistochemistry. The patient's symptoms included cough, chest pain, shortness of breath, hemoptysis, and hypodynamia. The primary focus of this paper is to discuss the impact of anti-PD-1 immunotherapy on PB. The patient experienced progression-free survival (PFS) of over 27 months following sintilimab second-line anti-PD-1 therapy. The patient has currently survived for nearly 40 months with a satisfactory quality of life.

High-sensitivity long-range surface plasmon resonance sensing assisted by gold nanoring cavity arrays and nanocavity coupling.

In many of the existing refractive index (RI) sensing works, only the shape and size of plasmonic structures are usually taken into account, while the parameters of spacer layers are ignored. In this publication, we explored the long-range surface plasmon resonance (LRSPR) and Fabry-Pérot resonance coupling effects of our proposed gold nanoring cavity array/spacer layer/Au mirror/glass substrate. Both the RI sensitivity and full width at half-maximum (FWHM) values were superior than those of conventional surface plasmon resonance substrates. We discussed the tunability of the RI sensitivity through changing the RI and thickness of the spacer layer. Then, under the optimized parameter conditions of the spacer layer, the geometry parameters (including size, gap and periodicity) of gold nanoring cavity arrays were tuned to optimize the best RI sensitivity. Finally, we broke the structural symmetry of a nanoring cavity to introduce Fano resonances into our system, and a high RI sensitivity and figure-of-merit (FOM) of 695 nm per RIU (refractive index unit) and 96.5, respectively, were achieved when the breaking angle θ was 30°. This study opens up many possibilities for boosting the FOM of RI sensing by taking into account the hybridization effects of localized surface plasmon resonance, LRSPR, and Fabry-Pérot and Fano resonances.

Prognostic Value of a CT Radiomics-Based Nomogram for the Overall Survival of Patients with Nonmetastatic BCLC Stage C Hepatocellular Carcinoma after Stereotactic Body Radiotherapy.

Purpose: This study aimed to investigatie the feasibility of pretherapeutic CT radiomics-based nomograms to predict the overall survival (OS) of patients with nondistant metastatic Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) undergoing stereotactic body radiotherapy (SBRT). Methods: A retrospective review of 137 patients with nondistant metastatic BCLC-C HCC who underwent SBRT was made. Radiomics features distilled from pretherapeutic CT images were selected by the method of LASSO regression for radiomics signature construction. Then, the clinical model was constructed based on clinical characteristics. A radiomics nomogram was constructed using the radiomics score (Rad-score) and clinical characteristics to predict post-SBRT OS in BCLC-C HCC patients. An analysis of discriminatory ability and calibration was performed to confirm the efficacy of the radiomics nomogram. Results: In order to construct the radiomic signature, seven significant features were selected. Patients were divided into low-risk (Rad-score < -0.03) and high-risk (Rad-score ≥ -0.03) groups based on the best Rad-score cutoff value. There were statistically significant differences in OS both in the training set (p < 0.0001) and the validation set (p=0.03) after stratification. The C-indexes of the radiomics nomogram were 0.77 (95% CI: 0.72-0.82) in the training set and 0.71 (95% CI: 0.61-0.81) in the validation set, which outperformed the clinical model and radiomics signature. An AUC of 0.76, 0.79, and 0.84 was reached for 6-, 12-, and 18-month survival predictions, respectively. Conclusions: The predictive nomogram that combines radiomic features with clinical characteristics has great prospects for application in the prediction of post-SBRT OS in nondistant metastatic BCLC-C HCC patients.

Research on Circular RNA Expression Profiles in the Photoaging Mouse Model.

Background: Nude mouse has been widely used to study photoaging induced by long-term chronic UV exposure. Circular RNAs (circRNAs) have been previously identified in several diseases. However, the roles of circRNAs in photoaging and potential regulatory mechanisms remain unclear. Objectives: To identify specific circRNAs differentially expressed in photoaged skin and investigate their potential role in aging. Materials and Methods: In this study, we screened out the microarray data to profile the expression of circRNAs. The circRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. Results: 36 circRNAs were identified to be differentially expressed between the UV group and control group (fold change > 1.5; P < 0.05), including 6 upregulated and 30 downregulated circRNAs. GO and KEGG biological pathway analyses indicated that the changes in circRNAs were associated with cancer, inflammation, oxidative stress, and metabolism. Conclusions: This present study revealed a circRNAs expression profiling in vivo. These findings not only provide a new possibility to prevent the occurrence of photoaging but also have therapeutic values for photoaging and associated skin diseases.

Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging.

Photoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and elastin degeneration, ultimately leads to skin photoaging, manifested by skin redness, coarse wrinkles, and pigmentation even skin cancer. There has been a large demand of effective prevention and medications but approaches in the current management of photoaging are very limited. In the previous study, we found that a non-coding circular RNA circ_0011129 acts as a miR-6732-5p adsorption sponge to inhibit the reduction of type I collagen and the denaturation and accumulation of elastin in UVA-induced HDF cells photoaging model. However, in vivo instability and efficient delivery to the target cell of circRNA is a major challenge for its clinical application. Therefore, improving its stability and delivery efficiency are desired. In this study, we proposed a strategy of delivering circ_0011129 with small extracellular vesicles (sEVs) from human adipose-derived stem cells (hADSCs) to intervene in the photoaging process. The results showed that sEVs from hADSCs in 3D bioreactor culture (3D-sEVs) can prevent photoaging. Consequently, by overexpressing circ_0011129 in hADSCs, we successfully loaded it into 3D-sEVs (3D-circ-sEVs) and its protective effect was better. Our studies provide a novel approach to preventing skin photoaging, which has important clinical significance and application value for the development of non-coding RNA drugs to treat skin photoaging. We first screened out hADSCs-derived sEVs with excellent anti-oxidant effects. We then compared the sEVs collected from traditional 2D culture with 3D bioreactor culture. By miRNA-seq and GEO data analysis, we found that miRNAs in 3D-sEVs were enriched in cell activities related to apoptosis, cellular senescence, and inflammation. Subsequently, we prepared circ_0011129-loaded 3D-sEVs (3D-circ-sEVs) by overexpressing it in hADSCs for the treatment of photoaging in vitro. We proved that 3D-circ-sEVs can interfere with the process of cell photoaging and protect cells from UVA radiation damage, as well as in a H2O2-induced oxidative stress model.

The Efficacy and Safety of Anlotinib Alone and in Combination with Other Drugs in Advanced Lung Cancer: A Retrospective Cohort Study.

OBJECTIVE: Lung cancer is a disease associated with high levels of morbidity and mortality, with approximately 2.1 million new cases every year. Anlotinib is a new small-molecule multitarget tyrosine kinase inhibitor independently developed in China that can inhibit the formation of tumor blood vessels and has a therapeutic effect on various cancers. However, the application of anlotinib in lung cancer needs further investigation. METHODS: We collected the progress notes of 43 patients with advanced lung cancer treated at the Oncology Department of Guangzhou Chest Hospital from March 2019 to March 2021. Additionally, we assessed the differences between drug combination therapy and single-drug therapy among patients treated with anlotinib. RESULTS: Patients in both the anlotinib-combination and anlotinib-monotherapy groups experienced remission; however, the overall disease control rate in the anlotinib-combination group was higher than that in the anlotinib-monotherapy group. Reexamination via computed tomography showed that patients in the anlotinib-combination group had better recovery than those in the anlotinib-monotherapy group. Although the overall incidence of adverse reactions in the anlotinib-combination group was higher than that in the monotherapy group, most of the adverse reactions were I-II levels and improved after symptomatic treatment. CONCLUSION: Anlotinib combined with other therapies is better than anlotinib alone for the management of patients with advanced lung cancer.

Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) is a skin cancer type characterized by a high degree of immune cell infiltration. The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients' risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.

Concomitant Pulmonary Tuberculosis Impair Survival in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinoma Patients Receiving EGFR-Tyrosine Kinase Inhibitor.

OBJECTIVE: Limited studies have clearly demonstrated the effect of EGFR-TKI in the treatment of EGFR mutant NSCLC patients with underlying pulmonary disease, like pulmonary tuberculosis (PTB). Here, we conducted the study to evaluate the impact of PTB on survival of Chinese EGFR mutant lung adenocarcinoma (LUAD) patients that underwent EGFR-TKI treatment. METHODS: Clinicopathologic data of 1448 LUAD patients harboring EGFR mutations from the Guangzhou Chest Hospital between 2017 and 2019 were reviewed retrospectively. Patients receiving EGFR-TKI treatment were divided into PTB and non-PTB groups. The differences in response to EGFR-TKIs and survival between the two groups were assessed. RESULTS: After EGFR-TKIs treatment, the objective response rate (58.14% vs 47.62%) as well as disease control rate (97.67% vs 85.71%) were higher in the non-PTB group than in the PTB group, but there was no statistical difference. In the survival analysis, both the median progression-free survival (7.47 months vs 11.77 months, p = 0.038) and the overall survival (13.00 months vs 20.00 months, p = 0.001) were significantly shorter in the PTB group than in the non-PTB group. Furthermore, for patients with 19Del mutation, or metastases sites less than 3, or using first-line EGFR-TKI, EGFR-TKIs treatment significantly prolonged the median PFS and OS in patients without PTB. CONCLUSION: LUAD patients with concomitant PTB have a poor response to EGFR-TKI treatment, especially in terms of survival outcome.

Clinical efficacy of the modified Helicobacter pylori eradication therapy for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a meta analysis.

BACKGROUND: Helicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP. METHODS: We searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I) statistic. RESULTS: A total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29-0.47). The combined estimate is I = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50-0.76), 0.16 (95% CI: 0.05-0.30), 0.38 (95% CI: 0.20-0.55), and 0.57 (95% CI: 0.08-1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries. CONCLUSION: Therefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

Simulation of climate change and thinning effects on productivity of Larix olgensis plantations in northeast China using 3-PGmix model.

Understanding the effects of thinning on forest productivity under climate change is vital to adaptive forest management. In the present study, the 3-PGmix model was applied to simulate the thinning effects on productivity of Larix olgensis plantations under climate change using 164 sample plots collected from the 6th, 7th and 8th National Forest Inventories in Jilin Province, northeast China. Climate scenarios of RCP 4.5 and RCP 8.5 were adopted from 2011 to 2100 with corresponding reference years (1981-2010). We simulated four cutting intensities: no-thinning, NT; low intensity thinning with 10% stem removal, LT; moderate thinning with 20% stem removal, MT and heavy thinning with 30% stem removal, HT for three times with 5- and 10-year thinning intervals. The results indicated that the mean net primary productivity (NPP) during the simulated 90 years was increased under RCP 4.5 and RCP 8.5. The LT and MT had positive but HT had negative effects on the mean NPP for the same climate scenario. Increased thinning intensity facilitated the positive effects of climate change on NPP but without a significant interaction effect. During the simulation, LT had the highest NPP value and HT had the biggest NPP increase under future climate change. We also discussed the management of larch plantations under climate change and advocated low intensity thinning with 10-year thinning interval to gain maximum NPP for mitigating climate change.

Spatial variability in the amount of forest litter at the local scale in northeastern China: Kriging and cokriging approaches to interpolation.

Litter is essential to promote nutrient cycling and maintain the sustainability of forest resources. However, its variability has not been sufficiently studied at the local scale. The prediction of litter amount using ordinary cokriging with Pearson correlation analysis (COKP) and ordinary cokriging with principal component analysis (COKPCA) was compared with that using ordinary kriging (OK) based on cross-validation at the local scale of a 1-ha plot over natural spruce-fir mixed forest in Jilin Province, China. Litter samples in semidecomposed (F) and complete decomposed (H) horizons were collected using an equidistant grid point sampling of 10 m × 10 m. Pearson correlation analysis and principal component analysis (PCA) were used to confirm auxiliary variables. The results showed that the amount of litter was 19.65 t/ha in the F horizon and 10.37 t/ha in the H horizon. The spatial structure variance ratio in the H horizon was smaller than that in the F horizon, indicative of its stronger spatial autocorrelation. Spatial distributions of litter amount in both horizons exhibited a patchy and heterogeneous pattern. Of the selected stand characteristics and litter properties, litter moisture content indicated the strongest relationship with litter amount. Cross-validation revealed that COKPCA using the comprehensive score as an auxiliary variable produced the most accurate map. The average standard error and root-mean-square error between the predicted and measured values were always smaller, the mean error and mean standardized error were much closer to 0, and the root-mean-square standardized error was closer to 1 than COKP using litter moisture and OK. Therefore, a clear advantage of cokriging based on principal component analysis was observed and COKPCA was found to be a very useful approach for further interpolation prediction.

Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing.

PURPOSE: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. MATERIALS AND METHODS: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. RESULTS: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. CONCLUSION: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.

Long noncoding RNA DANCR in various cancers: a meta-analysis and bioinformatics.

BACKGROUND: Differentiation antagonizing non-protein-coding RNA (DANCR) is a novel long noncoding RNA. Recent studies have shown that DANCR is aberrantly expressed in several types of cancer and is associated with poor outcomes. However, the clinical diagnostic significance of DANCR in tumors is not completely understood. METHODS: We searched the PubMed, Medline, Web of Science, EMBASE, Cochrane Library, and Ovid databases (up to December 30, 2018) for relevant literature. A total of 11 studies with 945 cancer patients were included in the present meta-analysis. We further validated the results using The Cancer Genome Atlas (TCGA) dataset. RESULTS: High expression of DANCR significantly predicted poor overall survival (low expression group vs high expression group; HR =0.56, 95% CI=[0.43, 0.72], =0.000); this was validated using TCGA. Moreover, DANCR expression was associated with advanced tumor node metastasis stage (I+II:III+IV; OR=0.22, 95% CI=[0.14, 0.35], P=0.001) and lymph node metastasis (no:yes; OR=0.21, 95% CI=[0.13, 0.35], P=0.001). CONCLUSION: Our results suggest that elevated DANCR is related to poor clinical outcomes and could serve as a potential prognostic biomarker of cancer.

[Gefitinib versus Erlotinib as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer].

OBJECTIVE: To compare the efficacy of the erlotinib versus gefitinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. METHODS: Fifty patients with untreated advanced EGFR mutation- positive NSCLC were randomly divided into gefitinib group (n=27) and erlotinib group (n=23). The progression-free survival, objective response rate and disease control rate were evaluated to compare the efficacy of gefitinib and erlotinib. RESULTS: There were no significant differences in the objective response rate (P=0.711) and disease control rate (P=0.861) between the two groups. The progression-free survival of gefitinib group and erlotinib group was 8.0 months and 10.0 months, respectively. The efficacy of the two drugs was similar (P=0.293). CONCLUSION: There is no significant differences between gefitinib and erlotinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

[Inhibitory effect of SHP-1 gene transfer on the proliferation of breast cancer cell line MDA-MB-231].

OBJECTIVE: To observe SHP-1 protein expression in breast cancer cell line MDA-MB-231 before and after SHP-1 gene transfer and its effect on the proliferation of MDA-MB-231 cells. METHODS: The eukaryotic expression vector pEGFP-C3-SHP-1 was constructed and transfected into breast cancer cell line MDA-MB-231 via Lipofectamine 2000, and the positive clones were selected using G418. SHP-1 expression in MDA-MB-231 cells was detected with immunocytochemistry and Western blotting, and the cell growth curve was observed using MTT assay. RESULTS: SHP-1 was highly expressed in transfected MDA-MB-231 cells, whose proliferation was significantly inhibited (P<0.05). CONCLUSION: SHP-1 gene transfer into MDA-MB-231 cells results in inhibition of the cell proliferation.