Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

Immune Rejection Mediated by prf1 and gzmb Affects the Colonization of Fat Greenling (Hexagrammos otakii) Spermatogonia in Heterotransplantation.

Fish germ cell transplantation holds great potential for conserving endangered species, improving cultured fish breeds, and exploring reproductive techniques. However, low transplantation efficiency is a common issue in heterotransplantation. This study transplanted fat greenling (Hexagrammos otakii) spermatogonia into the testes of spotted sea bass (Lateolabrax maculatus) to investigate factors that might affect the colonization and fixation of heterologous transplanted germ cells. Results indicated that transplanted fat greenling spermatogonia cells were successfully detected in the early transplantation phase in spotted sea bass. Their numbers gradually decreased over time, and after 10 days post-transplantation, more than 90% of the transplanted cells underwent apoptosis. Transcriptome sequencing analysis of the testes of spotted sea bass and fat greenling spermatogonia on days 1 and 10 post-transplantation revealed that this apoptosis process involved many immune-related genes and their associated signaling pathways. Acute immune rejection marker genes prf1 and gzmb were detected in the spotted sea bass testes, while immune tolerance genes lck and zap-70 were expressed in the fat greenling spermatogonia. Additionally, differential expression of prf1 and gzmb genes was screened from spotted sea bass, with experimental evidence indicating that PRF1 and GZMB protein from spotted sea bass primarily induce apoptosis in transplanted fat greenling spermatogonia via the mitochondrial apoptosis pathway, at the protein level. This suggests that the difficulties in heterotransplantation are primarily related to acute immune rejection, with PRF1 and GZMB playing significant roles.

Radiotherapy Improves Survival of Patients With Lymphovascular Invasion in pT1b Esophageal Squamous Cell Cancer After Endoscopic Submucosal Dissection.

INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC. METHODS: This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared. RESULTS: Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI+ group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P = 0.050; 5-year DFS: 92.9% vs 42.6%, P = 0.010). In the LVI- group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P = 0.148; 5-year DFS: 84.2% vs 84.7%, P = 0.907). The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI+ group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI- group without radiotherapy. DISCUSSION: Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI+ other than LVI- after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population.

300 Million years of coral treaders (Insecta: Heteroptera: Hermatobatidae) back to the ocean in the phylogenetic context of Arthropoda.

Among hundreds of insect families, Hermatobatidae (commonly known as coral treaders) is one of the most unique. They are small, wingless predaceous bugs in the suborder Heteroptera. Adults are almost black in colour, measuring about 5 mm in body length and 3 mm in width. Thirteen species are known from tropical coral reefs or rocky shores, but their origin and evolutionary adaptation to their unusual marine habitat were unexplored. We report here the genome and metagenome of Hermatobates lingyangjiaoensis, hitherto known only from its type locality in the South China Sea. We further reconstructed the evolutionary history and origin of these marine bugs in the broader context of Arthropoda. The dated phylogeny indicates that Hexapoda diverged from their marine sister groups approximately 498 Ma and that Hermatobatidae originated 192 Ma, indicating that they returned to an oceanic life some 300 Myr after their ancestors became terrestrial. Their origin is consistent with the recovery of tropical reef ecosystems after the end-Triassic mass extinction, which might have provided new and open niches for them to occupy and thrive. Our analyses also revealed that both the genome changes and the symbiotic bacteria might have contributed to adaptations necessary for life in the sea.

Research on Robot Screwing Skill Method Based on Demonstration Learning.

A robot screwing skill learning framework based on teaching-learning is proposed to improve the generalization ability of robots for different scenarios and objects, combined with the experience of a human operation. This framework includes task-based teaching, learning, and summarization. We teach a robot to twist and gather the operation's trajectories, define the obstacles with potential functions, and counter the twisting of the robot using a skill-learning-based dynamic movement primitive (DMP) and Gaussian mixture model-Gaussian mixture regression (GMM-GMR). The hole-finding and screwing stages of the process are modeled. In order to verify the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios, obstacle avoidance trends and tightening experiments were conducted. Obstacle avoidance and tightening experiments were conducted on the robot tightening platform for bolts, plastic bottle caps, and faucets. The robot successfully avoided obstacles and completed the twisting task, verifying the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios.

Electronic Interactions on Platinum/(Metal-Oxide)-Based Photocatalysts Boost Selective Photoreduction of CO2 to CH4.

By supporting platinum (Pt) and cadmium sulfide (CdS) nanoparticles on indium oxide (In2 O3 ), we fabricated a CdS/Pt/In2 O3 photocatalyst. Selective photoreduction of carbon dioxide (CO2 ) to methane (CH4 ) was achieved on CdS/Pt/In2 O3 with electronic Pt-In2 O3 interactions, with CH4 selectivity reaching to 100 %, which is higher than that on CdS/Pt/In2 O3 without electronic Pt-In2 O3 interactions (71.7 %). Moreover, the enhancement effect of electronic Pt-(metal-oxide) interactions on selective photoreduction of CO2 to CH4 also occurs by using other common metal oxides, such as photocatalyst supports, including titanium oxide, gallium oxide, zinc oxide, and tungsten oxide. The electronic Pt-(metal-oxide) interactions separate photogenerated electron-hole pairs and convert CO2 into CO2 δ- , which can be easily hydrogenated into CH4 via a CO2 δ- →HCOO*→HCO*→CH*→CH4 path, thus boosting selective photoreduction of CO2 to CH4 . This offers a new way to achieve selective photoreduction of CO2 .

MiR-323a-3p acts as a tumor suppressor by suppressing FMR1 and predicts better esophageal squamous cell carcinoma outcome.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has unfavorable outcomes with the highest incidence seen in China. Accordingly, exploring effective molecular biomarkers is of great value. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and modulate numerous biological processes in tumors. Our study aimed to identify prognostic miRNAs and investigate their role in ESCC. METHODS: Prognosis-related plasma miRNAs were detected by miRNA microarray and qRT-PCR. Functional assays and molecular mechanism studies were used to investigate the role of miRNA in ESCC. RESULTS: Over-expression of miR-323a-3p was associated with a favorable prognosis. MiR-323a-3p negatively regulated proliferation, migration, and invasion. Through biological predictions, the fragile X mental retardation 1 (FMR1) was found to be a potential target of miR-323a-3p. Further investigation revealed that miR-323a-3p directly targeted and suppressed FMR1. MiR-323a-3p and FMR1 mRNA, as well as miR-323a-3p and the FMR1-encoded protein FMRP, showed negative correlations. Luciferase activity of FMR1-3'-UTR, but not mutant counterparts, was decreased by mimic compared with that of the control. The compromised cell proliferation, migration, and invasion induced by transfection with miR-323a-3p mimic were rescued by transfection with a FMR1 expression plasmid. Tumors induced by miR-323a-3p overexpressed ESCC cells grew significantly slower in vivo and resulted in smaller tumor masses. Metastatic lung colonization was also inhibited by miR-323a-3p overexpression. CONCLUSIONS: MiR-323a-3p was significantly associated with survival and acted as a tumor suppressor by inhibiting proliferation, migration, and invasion via the regulation of FMR1. MiR-323a-3p is a promising biomarker and may be a potential therapeutic target.

Using suicide notes to understand suicide among cancer patients: A mixed-method study.

BACKGROUND: Cancer patients are at risk of suicide. However, no studies have used suicide notes to investigate their expressed reasons for suicide. The objectives of this study were to compare the characteristics between note leavers and non-leavers among cancer suicide cases and to understand the patterns in expressed reasons for suicide using suicide notes. METHOD: Suicide cases (2012-2017) were identified from the Hong Kong Coroner's Court reports, which provide detailed information as well as the content of suicide notes. Bivariate tests and multiple logistic regression were performed to compare the characteristics of note leavers and non-leavers among suicide cases with cancer. Thematic analysis was performed on suicide notes to extract themes of expressed reasons for suicides by cancer status and age group. RESULTS: Among cancer suicide cases and compared to non-leavers, note leavers were younger, more likely to be male, use non-violent suicide methods, have better housing conditions, and live alone. Suffering from physical disease was a major theme identified among cancer note leavers across all age groups. Young and middle-aged non-cancer note leavers had various themes identified. Physical illness was the major theme for elderly non-cancer note leavers. CONCLUSIONS: Cancer note leavers had unique characteristics and suffering from physical illness was the major expressed reason identified in the suicide notes. Healthcare professionals should pay attention to the mental as well as the physical needs of patients. Improving quality of life and regaining control of life are vital for suicide prevention among cancer patients.

Identification and functional analysis of dual-specificity phosphatases (DUSP) genes in Japanese flounder (Paralichthys olivaceus) against temperature and Edwardsiella tarda stress.

Dual-specificity Phosphatases (DUSPs) are not only the key regulators of dephosphorylating and inactivating mitogen-activated protein kinases (MAPKs), but play a crucial role in the immune response. However, the role of DUSP genes in Japanese flounder (PoDUSPs) is still unclear. In this study, 28 DUSP genes in Japanese flounder were identified and classified based on the whole genome database. Phylogenetic analysis and protein structure analysis revealed that DUSPs had highly conserved domains in teleosts. Molecular evolution analysis indicated that the PoDUSP genes were conservative during evolution and were functional-constrained. Meanwhile, PoDUSP genes were found to express in different embryonic and larval stages which might play the role of sentinel in healthy organisms. Furthermore, PoDUSP genes' expression profiles after temperature stress and Edwardsiella tarda (E. tarda) infection were determined in Japanese flounder without precedent, and the results demonstrated that Podusp1, Podusp2 and Podusp16 were more respective to temperature variation whereas Podusp1 and Podusp6 were more respective to E. tarda infection. In summary, our results provide useful resources for understanding the immune responsibilities of DUSP genes in flatfish.

Stage correlation of symbiotic bacterial community and function in the development of litchi bugs (Hemiptera: Tessaratomidae).

Bacterial symbionts of insects have been shown to play important roles in host fitness. However, little is known about the bacterial community of Tessaratoma papillosa which is one of the most destructive pests of the well-known fruits Litchi chinensis Sonn and Dimocarpus longan Lour in Oriental Region, especially in South-east Asia and adjacent areas. In this study, we surveyed the bacterial community diversity and dynamics of T. papillosa in all developmental stages with both culture-dependent and culture-independent methods by the third-generation sequencing technology. Five bacterial phyla were identified in seven developmental stages of T. papillosa. Proteobacteria was the dominant phylum and Pantoea was the dominant genus of T. papillosa. The results of alpha and beta diversity analyses showed that egg stage had the most complex bacterial community. Some of different developmental stages showed similarities, which were clustered into three phases: (1) egg stage, (2) early nymph stages (instars 1-3), and (3) late nymph stages (instars 4-5) and adult stage. Functional prediction indicated that the bacterial community played different roles in these three phases. Furthermore, 109 different bacterial strains were isolated and identified from various developmental stages. This study revealed the relationship between the symbiotic bacteria and the development of T. papillosa, and may thus contribute to the biological control techniques of T. papillosa in the future.

Home as the first site for suicide prevention: a Hong Kong experience.

INTRODUCTION: There has been little research into at-home suicide cases globally, and particularly in Asian regions. This study aimed to investigate the differences in characteristics between suicide cases in Hong Kong that occurred at home and elsewhere; identify at-home suicide hotspots in the community and compare the differences in area-level characteristics between suicide hotspots and other areas. METHODS: Suicide cases (2013-2017) were identified from Hong Kong Coroner's Court reports. Area-level socioeconomic data were retrieved from the 2016 Hong Kong census. Wilcoxon signed-rank tests, χ2 tests and multiple logistic regression models were applied to compare differences in characteristics between people committing suicide at home and elsewhere. Global hotspot tests (Moran's I and Getis-Ord General G) and local analysis (Getis-Ord Gi*) identified at-home suicide community hotspots. The Wilcoxon signed-rank test was used to compare differences in area-level characteristics between at-home suicide hotspots and non-hotspots. RESULTS: About 60% of suicide cases in Hong Kong occurred at home. Being female, widowed and/or living alone were significant predictors of at-home suicide cases. A U-shaped association between age and at-home suicide was identified, with 32 years of age being the critical turning point. An at-home suicide hotspot was identified in the north-western region of Hong Kong, which had lower median household income, higher income inequality and higher percentages of households with single elderly people, and new arrivals, compared with other areas. CONCLUSION: Suicide prevention should start at home by restricting access to suicide methods. Community-based suicide prevention interventions with improvement of social services should target vulnerable members in identified suicide hotspots.

Evaluation of Sample Preservation Approaches for Better Insect Microbiome Research According to Next-Generation and Third-Generation Sequencing.

The microbial communities associated with insects play critical roles in many physiological functions such as digestion, nutrition, and defense. Meanwhile, with the development of sequencing technology, more and more studies begin to focus on broader biodiversity of insects and the corresponding mechanisms of insect microbial symbiosis, which need longer time collecting in the field. However, few studies have evaluated the effect of insect microbiome sample preservation approaches especially in different time durations or have assessed whether these approaches are appropriate for both next-generation sequencing (NGS) and third-generation sequencing (TGS) technologies. Here, we used Tessaratoma papillosa (Hemiptera: Tessaratomidae), an important litchi pest, as the model insect and adopted two sequencing technologies to evaluate the effect of four different preservation approaches (cetyltrimethylammonium bromide (CTAB), ethanol, air dried, and RNAlater). We found the samples treated by air dried method, which entomologists adopted for morphological observation and classical taxonomy, would get worse soon. RNAlater as the most expensive approaches for insect microbiome sample preservation did not suit for field works longer than 1 month. We recommended CTAB and ethanol as better preservatives in longer time field work for their effectiveness and low cost. Comparing with the full-length 16S rRNA gene sequenced by TGS, the V4 region of 16S rRNA gene sequenced by NGS has a lower resolution trait and may misestimate the composition of microbial communities. Our results provided recommendations for suitable preservation approaches applied to insect microbiome studies based on two sequencing technologies, which can help researchers properly preserve samples in field works.

Postoperative radiotherapy is effective in improving survival of patients with stage pIII-N2 non-small-cell lung Cancer after pneumonectomy.

BACKGROUND: There were few reports of postoperative radiotherapy (PORT) in stage pIII-N2 Non-small-cell Lung Cancer (NSCLC) patients receiving pneumonectomy followed by adjuvant chemotherapy. This study aims to evaluate safety and efficacy of PORT among these patients. METHODS: Between Jan. 2004 and Dec. 2015, stage pIII-N2 NSCLC patients receiving pneumonectomy and adjuvant chemotherapy with or without PORT in our institution were retrospectively reviewed. RESULTS: Totally 119 patients were included, 32 patients receiving adjuvant chemotherapy and PORT (PORT group) and 87 receiving adjuvant chemotherapy alone (Control group). There were more patients with non-R0 resection in PORT group than Control group (25% vs. 8%, p = 0.031). In PORT group, ≥Grade 2 radiation-induced pneumonitis was 2/32. No severe radiation-related heart injury was observed. There was no PORT-related death. Of all patients, median follow-up time was 25 months. Median overall survival time (mOS) and median disease-free survival time (mDFS) were 46 months and 15 months, respectively. The PORT group had significantly better OS (not reached vs. 34 months, p = 0.003), DFS (19 months vs. 13 months, p = 0.024), local recurrence free survival (LRFS, p = 0.012), and distant metastasis free survival (DMFS, p = 0.047) than the Control group. As for failure pattern, PORT significantly reduced local regional failure rate (39.1% vs. 15.6%, p = 0.016). In subgroup analysis, patients with R0 resection (n = 104), OS and LRFS in PORT group were significantly longer, and PORT tended to increase DFS and DMFS. CONCLUSION: For patients with stage pIII-N2 NSCLC after pneumonectomy and adjuvant chemotherapy, PORT can improve OS, DFS, LRFS and DMFS with tolerable toxicity.

Selective CO Evolution from Photoreduction of CO2 on a Metal-Carbide-Based Composite Catalyst.

A selective CO evolution from photoreduction of CO2 in water was achieved on a noble-metal-free, carbide-based composite catalyst, as demonstrated by a CO selectivity of 98.3% among all carbon-containing products and a CO evolution rate of 29.2 µmol h-1, showing superiority to noble-metal-based catalyst. A rapid separation of the photogenerated electron-hole pairs and improved CO2 adsorption on the surface of the carbide component are responsible for the excellent performance of the catalyst. The high CO selectivity is accompanied by a predominant H2 evolution, which is believed to provide a proton-deficient environment around the catalyst to favor the formation of hydrogen-deficient carbon products. The present work provides general insights into the design of a catalyst with a high product selectivity and also the carbon evolution chemistry during a photocatalytic reaction.

Photocatalytic CO2 Reduction by Carbon-Coated Indium-Oxide Nanobelts.

Indium-oxide (In2O3) nanobelts coated by a 5-nm-thick carbon layer provide an enhanced photocatalytic reduction of CO2 to CO and CH4, yielding CO and CH4 evolution rates of 126.6 and 27.9 µmol h-1, respectively, with water as reductant and Pt as co-catalyst. The carbon coat promotes the absorption of visible light, improves the separation of photoinduced electron-hole pairs, increases the chemisorption of CO2, makes more protons from water splitting participate in CO2 reduction, and thereby facilitates the photocatalytic reduction of CO2 to CO and CH4.

MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAD) is considered to be a highly aggressive disease with heterogeneous prognosis and the molecular mechanisms underlying tumor progression remain elusive. Growing evidence demonstrates that the dysregulation of microRNAs (miRNAs) plays an important role in various tumor processes. The aim of this study is to discover prognostic miRNA and investigate its role involved in progression of LAD. METHODS: Prognosis related miRNA was detected by miRNA microarray using formalin-fixed paraffin-embedded (FFPE) specimens from 87 patients with IIIA-N2 LAD. The cell proliferation was evaluated by Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS), and the migration/invasion was evaluated by transwell assay. The bioinformatics methods and luciferase reporter assay were applied to detect the relationship between miRNA and its target. The mRNA and protein levels of miRNA target were determined by quantitative real time polymerase chain reaction (qRT-PCR) analysis, western blot and enzyme-linked immunosorbent assay (ELISA). Changes of angiogenesis induced by miRNA was evaluated by human umbilical vein endothelial cell (HUVEC) tube formation assay. Immunohistochemistry (IHC) analysis was performed in FFPE specimens of patients to evaluate the correlation between miR-29c with microvessel density (MVD) and vascular endothelial growth factor A (VEGFA) expression. RESULTS: MiR-29c expression downregulation was significantly associated with unfavorable prognosis in IIIA-N2 LAD. MiR-29c inhibited cell proliferation, migration and invasion in cell lines. Integrated analysis revealed that VEGFA was a direct target of miR-29c. MiR-29c reduced the capability of tumor cells to promote HUVEC tube formation. The compromised cell proliferation, migration/invasion and angiogenesis induced by miR-29c mimic transfection were reversed by transfection of VEGFA expression plasmid. Furthermore, the correlation of miR-29c with MVD and VEGFA was confirmed in patients' samples. CONCLUSIONS: MiR-29c acts as a tumor suppressor by targeting VEGFA and may represent a promising prognostic biomarker as well as a potential therapeutic target for LAD.

Intensity-Modulated Radiation Therapy May Improve Local-Regional Tumor Control for Locally Advanced Non-Small Cell Lung Cancer Compared With Three-Dimensional Conformal Radiation Therapy.

BACKGROUND: Consistent results are lacking as regards the comparative effectiveness of intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Patients treated with definitive radiotherapy (RT) between 2002 and 2010 were retrospectively reviewed. Overall survival (OS), local-regional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were compared among patients irradiated with different techniques. The association between RT technique and survival indexes was assessed in a Cox proportional hazard regression model. Propensity score matching (PSM) was used to balance known confounding factors. RESULTS: A total of 652 patients were eligible for analysis, including 206 with 3DCRT and 446 with IMRT. The median OS of the 3DCRT and IMRT groups were 19.4 and 23.3 months, with the 5-year rate of 13% and 19%, respectively (p = .043). Multivariate analysis identified IMRT as an independent favorable factor associated with LRPFS and DMFS. PSM analysis further verified the beneficial effect of IMRT on LRPFS. No difference in OS or PFS was observed between the two techniques. Subgroup analysis revealed that IMRT might be differentially more effective in both OS and LRPFS among patients who were female, nonsmokers, with adenocarcinoma, or without weight loss. There was a significant reduction of lung toxicity and similar esophagus toxicity in the IMRT group when compared with the 3DCRT group. CONCLUSION: IMRT may confer superior LRPFS and comparable OS than can be achieved with 3DCRT in LA-NSCLC, along with the reduction of pulmonary toxicity. IMPLICATIONS FOR PRACTICE: Based on the largest number of patients from a single institution, the present study demonstrated that intensity-modulated radiotherapy (IMRT) could provide superior local-regional progression-free survival and similar overall survival compared with the traditional three-dimensional conformal radiotherapy (3DCRT) for stage III non-small cell lung cancer (NSCLC). IMRT was also found to be associated with the significantly decreased incidence of pulmonary toxicity. These results suggest that IMRT should be considered a surrogate for 3DCRT in locally advanced NSCLC and might be the preferred option for a female nonsmoker with adenocarcinoma and a potentially high risk of pulmonary toxicity from radiotherapy.

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.

Network analysis of histopathological image features and genomics data improving prognosis performance in clear cell renal cell carcinoma.

INTRODUCTION: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge. METHODS: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (n = 197) and validation (n = 84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators. RESULTS: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC) = 0.726, 3-year AUC = 0.727, and 5-year AUC = 0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUC = 0.682, 3-year AUC = 0.734, and 5-year AUC = 0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model. CONCLUSION: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.

Effects of Local Treatment in Combination with Systemic Therapy for Advanced Esophageal Cancer: A Systematic Review and Meta-analysis.

Purpose: Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC. Methods and Materials: A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests. Results: A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; P < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; P < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; P < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; P < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; P = .002). Conclusions: In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.