The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication.

IMPORTANCE: Generation of virus-host protein-protein interactions (PPIs) maps may provide clues to uncover SARS-CoV-2-hijacked cellular processes. However, these PPIs maps were created by expressing each viral protein singularly, which does not reflect the life situation in which certain viral proteins synergistically interact with host proteins. Our results reveal the host-viral protein-protein interactome of SARS-CoV-2 NSP3, NSP4, and NSP6 expressed individually or in combination. Furthermore, REEP5/TRAM1 complex interacts with NSP3 at ROs and promotes viral replication. The significance of our research is identifying virus-host interactions that may be targeted for therapeutic intervention.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

BACKGROUND AND AIMS: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. METHODS: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. RESULTS: Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. CONCLUSION: This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Convolutional neural network based anatomical site identification for laryngoscopy quality control: A multicenter study.

OBJECTIVES: Video laryngoscopy is an important diagnostic tool for head and neck cancers. The artificial intelligence (AI) system has been shown to monitor blind spots during esophagogastroduodenoscopy. This study aimed to test the performance of AI-driven intelligent laryngoscopy monitoring assistant (ILMA) for landmark anatomical sites identification on laryngoscopic images and videos based on a convolutional neural network (CNN). MATERIALS AND METHODS: The laryngoscopic images taken from January to December 2018 were retrospectively collected, and ILMA was developed using the CNN model of Inception-ResNet-v2 + Squeeze-and-Excitation Networks (SENet). A total of 16,000 laryngoscopic images were used for training. These were assigned to 20 landmark anatomical sites covering six major head and neck regions. In addition, the performance of ILMA in identifying anatomical sites was validated using 4000 laryngoscopic images and 25 videos provided by five other tertiary hospitals. RESULTS: ILMA identified the 20 anatomical sites on the laryngoscopic images with a total accuracy of 97.60 %, and the average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100 %, 99.87 %, 97.65 %, and 99.87 %, respectively. In addition, multicenter clinical verification displayed that the accuracy of ILMA in identifying the 20 targeted anatomical sites in 25 laryngoscopic videos from five hospitals was ≥95 %. CONCLUSION: The proposed CNN-based ILMA model can rapidly and accurately identify the anatomical sites on laryngoscopic images. The model can reflect the coverage of anatomical regions of the head and neck by laryngoscopy, showing application potential in improving the quality of laryngoscopy.

Comprehensive analysis of tumor immune microenvironment and prognosis of m6A-related lncRNAs in gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal roles in gastric cancer (GC) progression. The emergence of immunotherapy in GC has created a paradigm shift in the approaches of treatment, whereas there is significant heterogeneity with regard to degree of treatment responses, which results from the variability of tumor immune microenvironment (TIME). How the interplay between m6A and lncRNAs enrolling in the shaping of TIME remains unclear. METHODS: The RNA sequencing and clinical data of GC patients were collected from TCGA database. Pearson correlation test and univariate Cox analysis were used to screen out m6A-related lncRNAs. Consensus clustering method was implemented to classify GC patients into two clusters. Survival analysis, the infiltration level of immune cells, Gene set enrichment analysis (GSEA) and the mutation profiles were analyzed and compared between two clusters. A competing endogenous RNA (ceRNA) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied for the identification of pathways in which m6A-related lncRNAs enriched. Then least absolute shrinkage and selection operator (LASSO) COX regression was implemented to select pivotal lncRNAs, and risk model was constructed accordingly. The prognosis value of the risk model was explored. In addition, the response to immune checkpoint inhibitors (ICIs) therapy were compared between different risk groups. Finally, we performed qRT-PCR to detect expression patterns of the selected lncRNAs in the 35 tumor tissues and their paired adjacent normal tissues, and validated the prognostic value of risk model in our cohort (N = 35). RESULTS: The expression profiles of 15 lncRNAs were included to cluster patients into 2 subtypes. Cluster1 with worse prognosis harbored higher immune score, stromal score, ESTIMATE score and lower mutation rates of the genes. Different immune cell infiltration patterns were also displayed between the two clusters. GSEA showed that cluster1 preferentially enriched in tumor hallmarks and tumor-related biological pathways. KEGG pathway analysis found that the target mRNAs which m6A-related lncRNAs regulated by sponging miRNAs mainly enriched in vascular smooth muscle contraction, cAMP signaling pathway and cGMP-PKG signaling pathway. Next, eight lncRNAs were selected by LASSO regression algorithm to construct risk model. Patients in the high-risk group had poor prognoses, which were consistent in our cohort. As for predicting responses to ICIs therapy, patients from high-risk group were found to have lower tumor mutation burden (TMB) scores and account for large proportion in the Microsatellite Instability-Low (MSI-L) subtype. Moreover, patients had distinct immunophenoscores in different risk groups. CONCLUSION: Our study revealed that the interplay between m6A modification and lncRNAs might have critical role in predicting GC prognosis, sculpting TIME landscape and predicting the responses to ICIs therapy.

Risk stratification of LI-RADS M and LI-RADS 4/5 combined hepatocellular cholangiocarcinoma: prognostic values of MR imaging features and clinicopathological factors.

OBJECTIVES: To investigate the role of clinicopathological factors and MR imaging factors in risk stratification of combined hepatocellular cholangiocarcinoma (cHCC-CCA) patients who were classified as LR-M and LR-4/5. METHODS: We retrospectively identified consecutive patients who were confirmed as cHCC-CCA after surgical surgery in our institution from June 2015 to November 2020. Two radiologists evaluated the preoperative MR imaging features independently, and each lesion was assigned with a LI-RADS category. Preoperative clinical data were also collected. Multivariate Cox proportional hazards model was applied to separately identify the independent factors correlated with the recurrence of cHCC-CCAs in LR-M and LR-4/5. Risk stratifications were conducted separately in LR-M and LR-4/5. Recurrence-free survival (RFS) rates and overall survival (OS) rates were analyzed by using the Kaplan-Meier survival curves and log-rank test. RESULTS: A total of 131 patients with single primary lesion which met the 2019 WHO classification criteria were finally included. Corona enhancement, delayed central enhancement, and microvascular invasion (MVI) were identified as predictors of RFS in LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in LR-4/5. Based on the number of these independent predictors, patients were stratified into favorable-outcome groups (LR-ML subgroup and LR-4/5L subgroup) and dismal-outcome groups (LR-MH subgroup and LR-4/5H subgroup). The corresponding median RFS for LR-ML, LR-MH, LR-5L, and LR-5H were 25.6 months, 8.2 months, 51.7 months, and 18.1 months. CONCLUSION: Our study explored the prognostic values of imaging and clinicopathological factors for LR-M and LR-4/5 cHCC-CCA patients, and different survival outcomes were observed among four subgroups after conducting risk stratifications. KEY POINTS: • Corona enhancement, delayed central enhancement, and MVI were identified as predictors of RFS in cHCC-CCAs which were classified into LR-M. Mosaic architecture, CA19-9, and MVI were independently associated with RFS in cHCC-CCAs which were classified into LR-4/5. • Based on the identified risk factors, LR-M and LR-4/5 cHCC-CCA patients could be stratified into two subgroups respectively, with significantly different RFS and OS. • cHCC-CCA patients from LR-M did not always have worse RFS and OS than those from LR-4/5 in some cases.

Clinical Study on Systemic Lupus Erythematosus Complicated with Knee Bone Infarction.

Objective: The present study aims to (1) analyze the clinical characteristics and related influencing factors of knee bone infarction in systemic lupus erythematosus (SLE) and (2) improve the understanding of SLE complicated with knee bone infarction. Methods: The data of patients with SLE complicated with knee bone infarction were retrospectively analysed; patients with SLE during the same period who matched in age, gender, and disease duration were selected as control subjects, with a 1 : 1 ratio with the SLE group. The clinical data were collected to analyze the risk factors for SLE complicated with knee bone infarction. Results: In a total of 36 (6.4%) of 563 patients aged 19-33 (25.8 ± 4.8) years who had SLE during the same period, the disease was complicated with knee bone infarction. The diagnosis of knee bone infarction was made at an SLE duration of 7-65 (26.2 ± 15.7) months. During the SLE course, knee bone infarction occurred within 1 year in 6 cases (16.7%), within 1-5 years in 28 cases (77.8%), and in >5 years in 2 cases (5.6%). Raynaud's phenomenon incidence and anti-nRNP antibody positivity were significantly higher in the knee bone infarction group than in the control group (P < 0.01 and P < 0.05, respectively). The cumulative glucocorticoid dose at 1, 3, and 6 months was significantly higher in the knee bone infarction group than in the control group (P < 0.05). SLE complicated with knee necrosis had a statistically significant rank correlation with Raynaud's phenomenon (r = 0.445, P < 0.001), anti-nRNP antibody (r = 0.309, P=0.008), and renal injury (r = 0.252, P=0.032). The multivariate analysis of SLE complicated with knee bone infarction showed that Raynaud's phenomenon was an independent influencing factor for the complicated knee bone infarction in SLE patients (OR = 4.938, P=0.004), and the probability of SLE complicated with knee bone infarction in Raynaud's phenomenon positive patients was 4.938 times that of Raynaud's phenomenon negative patients. Conclusions: The risk of knee bone infarction was relatively high in patients with SLE within a 5-year disease course and in young patients. The risk factors were Raynaud's phenomenon, anti-nRNP antibody positivity, and early high-dose glucocorticoid therapy.

Circular RNA WHSC1 exerts oncogenic properties by regulating miR-7/TAB2 in lung cancer.

Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy.

HNRNPAB-regulated lncRNA-ELF209 inhibits the malignancy of hepatocellular carcinoma.

Our previous study demonstrated that heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) is a key gene that facilitates metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms behind this relationship are not fully understood. In our study, we utilized long-noncoding RNA (lncRNA) microarrays to identify a HNRNPAB-regulated lncRNA named lnc-ELF209. Our findings from chromatin immunoprecipitation assays indicate that HNRNPAB represses lnc-ELF209 transcription by directly binding to its promoter region. We also analyzed clinical samples from HCC patients and cell lines with quantitative real-time polymerase chain reactions, RNA in situ hybridization and immunohistochemistry, and found that there is a negative relationship between HNRNPAB and lnc-ELF209 expression. Up/downregulation assays and rescue assays indicate that lnc-ELF209 inhibits cell migration, invasion and epithelial-mesenchymal transition regulated by HNRNPAB. This suggests a new regulatory mechanism for HNRNPAB-promoted HCC progression. RNA pull-down and LC-MS/MS were used to determine triosephosphate isomerase, heat shock protein 90-beta and vimentin may be involved in the tumor-suppressed function of lnc-ELF209. Furthermore, we found lnc-ELF209 could stabilize TPI protein expression. We also found that lnc-ELF209 overexpression in HCCLM3 cell resulted in a lower rate of lung metastatic, which suggested a less aggressive HCC phenotype. Collectively, these findings offer new insights into the regulatory mechanisms that underlie HNRNPAB cancer-promoting activities and demonstrate that lnc-ELF209 is a HNRNPAB-regulated lncRNA that may play an important role in the inhibition of HCC progression.

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications.

BACKGROUND: Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy. METHODS: A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validation of immunogenomic classification was performed across six microarray datasets of 1406 samples. RESULTS: We found approximately half of gastric cancer samples to have higher immune cell infiltrates, PD-L1 expression, markers of cytolytic activity, and fewer copy number aberrations (all P < 0.05). We termed this group of tumours the Immune Class, which incorporated two components, namely Immune Activation and Immunosuppressive Subtype, according to immunosuppressive or activated microenvironment. Immune Activation Subtype was associated with improved survival in multivariate survival analysis and shared similar genomic characteristics with responders of anti-PD-1 therapy. Immunosuppressive Subtype featured high immune infiltration, stromal enrichment, and transforming growth factor (TGF)-ß signalling pathway activation and correlated with non-responsiveness signature of checkpoint blockade therapy, which might be suitable for anti-PD-L1 and anti-TGF-ß combined therapy. CONCLUSIONS: We proposed and independently validated three reproducible immune molecular subtypes of gastric cancer, which may provide implications for patient selection of immunotherapy.

Comparative efficacy and safety of immunosuppressive therapies for systemic sclerosis related interstitial lung disease: A Bayesian network analysis.

Objectives: Immunosuppressive therapies for the treatment of patients with systemic sclerosis (SSc) and SSc related interstitial lung diseases (SSc-ILD) include cyclophosphamide (CYC), mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX). The objectives were to compare and rank these therapies in term of forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLco) % predicted and adverse events (AEs).Methods: We present pooled estimates of mean difference (MD) and odds rates (ORs) with 95% confidence intervals (CIs) among different therapies. We also ranked these agents with surface under the cumulative ranking probability (SUCRA).Results: CYC plus AZA had the highest SUCRA probability (70%) on reducing risk of the deterioration of FVC compared with CYC, observation (OBS), MMF and AZA. While for the prevention of the deterioration of DLco, MMF showed the highest SUCRA probability (76%) compared with others. Moreover, AZA showed the lowest probability (32%) for AEs among active interventions.Conclusions: CYC plus AZA was the preferred immunosuppressive strategies compared to others on preventing the deterioration of FVC. MMF resulted with the highest probability as the best in preventing the deterioration of DLco. Monotherapy of AZA was less pulmonary function benefit but related less AEs.

[Vascular damage-related risk factors for erectile dysfunction in patients with type 2 diabetes mellitus: Analysis based on a nomogram model].

OBJECTIVE: To analyze vascular damage-related risk factors for ED in patients with type 2 diabetes mellitus (DM) and develop a nomogram for the prediction of the factors. METHODS: A total of 181 patients with type 2 DM were included for sexual function assessment, and the clinical data on vascular damage were retrieved from the patients system. After preprocessing, the data were described by the number and percentage of different types of cases and subjected to statistical analysis with the R software. The Lasso regression model was used to optimize feature selection. On the premise of the sample size required for logistic regression analysis according to the number of events per variable, multivariable logistic regression analysis was performed on the selected variables and a nomogram was developed for diabetes-induced erectile dysfunction (DIED). Then, the performance of the nomogram was evaluated with respect to its calibration, discrimination and clinical utility using Harrell's concordance index (C-index), the calibration plot and decision curve analysis, as well as bootstrapping for internal validation. RESULTS: ED was diagnosed in 90 (49.7%) of the 181 patients. The risk factors subjected to logistic regression analysis included the duration of DM (OR = 4.440, 95% CI: 1.594－13.105; OR = 7.667, 95% CI: 1.444－48.733), status of carotid intima-media thickness (c-IMT) (OR = 3.767, 95% CI: 1.194－12.691), diabetic retinopathy (DR) (OR = 5.382, 95% CI: 1.373－28.301), diabetic kidney disease (DKD) (OR = 4.959, 95% CI: 1.156－27.728), low-density lipoprotein cholesterol (LDL-C) (OR = 8.210, 95% CI: 2.027－43.507), red blood cell distribution width (RDW) (OR = 2.418, 95% CI: 1.021－5.826), and plasma fibrinogen (Fbg) (OR = 4.649, 95% CI: 2.001－11.339). The C-index of the DIED model was 0.911 (95% CI: 0.869－0.954). The curve representing the performance of the nomogram fit in well with that representing a perfect prediction by the calibration plot. Decision curve analysis indicated that the nomogram was clinically useful for predicting DIED in the type 2 DM patients at the possibility threshold of 6% to 93%. CONCLUSIONS: A nomogram was preliminarily developed for predicting the risk of DIED in type 2 DM patients with respect to the seven independent influencing factors, including the duration of DM, status of c-IMT, DR, DKD, LDL-C, RDW, and Fbg.

Prognostic alternative mRNA splicing signature in hepatocellular carcinoma: a study based on large-scale sequencing data.

Most genes are alternatively spliced and increasing number of evidences show that alternative splicing (AS) is modified and related to tumor progression. Systematic profiles of AS signature in hepatocellular carcinoma (HCC) is absent and urgently needed. Here, differentially spliced AS transcripts between HCC and non-HCC tissues were compared, prognosis-associated AS events by using univariate Cox regression analysis were selected. Our gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognostic AS signatures were then constructed for HCC prognosis prediction by Lasso regression model. We also analyzed splicing factors (SFs) regulating underlying mechanisms by Pearson correlation and then built corresponding regulatory networks. In addition, we explored the performance of AS signature in the mutated HCC samples. Genome-wide AS events in 377 HCC patients from TCGA were profiled. Among 34 163 AS events in 8985 genes, 3950 AS events in 2403 genes associated with overall survival (OS) significantly for HCC were detected. In addition, computational algorithm results showed that metabolic and ribosome pathways may be the potential molecular mechanisms regulating the poor prognosis. More importantly, survival-associated AS signatures revealed high performance in predicting HCC prognosis. The area under curve for AS signature was 0.806 in all HCC and 0.944 in TP53 mutated HCC samples at 2000 days of OS. We submitted prognostic SFs to build the AS regulatory network, from which we found prognostic AS events were significantly enriched in metabolism-related pathways. A robust AS signature for HCC patients and revealed the regulatory splicing networks contributing to the potential significantly enriched metabolism-related pathways.

Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients.

BACKGROUND: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients' prognosis. We aim to identify new prognostic markers for resected HCC patients. METHODS: 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a "9-gene signature" associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). RESULTS: We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001). CONCLUSIONS: The 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended.

Characterization of the Complete Chloroplast Genomes of Buddleja colvilei and B. sessilifolia: Implications for the Taxonomy of Buddleja L.

Buddleja colvilei Hook.f. & Thomson (Scrophulariaceae) is a threatened alpine plant with a distribution throughout the Himalayas, also used as an ornamental plant. The name Buddleja sessilifolia B.S. Sun ex S.Y. Pao was assigned in 1983 to a plant distributed throughout the Gaoligong Mountains, but the name was later placed in synonymy with B. colvilei in the Flora of China. In this study we sequenced the complete chloroplast (cp) genomes of two individuals of B. colvilei and three individuals of B. sessilifolia from across the range. Both molecular and morphological analysis support the revision of B. sessilifolia. The phylogenetic analysis constructed with the whole cp genomes, the large single-copy regions (LSC), small single-copy regions (SSC), inverted repeat (IR) and the nuclear genes 18S/ITS1/5.8S/ITS2/28S all supported B. sessilifolia as a distinct species. Additionally, coalescence-based species delimitation methods (bGMYC, bPTP) using the whole chloroplast datasets also supported B. sessilifolia as a distinct species. The results suggest that the B. sessilifolia lineage was early diverging among the Asian Buddleja species. Overall gene contents were similar and gene arrangements were found to be highly conserved in the two species, however, fixed differences were found between the two species. A total of 474 single nucleotide polymorphisms (SNPs) were identified between the two species. The Principal Coordinate Analysis of the morphological characters resolved two groups and supported B. sessilifolia as a distinct species. Discrimination of B. colvilei and B. sessilifolia using morphological characters and the redescription of B. sessilifolia are detailed here.

Prolonged survival of patients with EGFR-mutated non-small cell lung cancer with solitary brain metastases treated with surgical resection of brain and lung lesions followed by EGFR TKIs.

BACKGROUND: The standard combination of initial and subsequent treatments of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with solitary brain metastases (BM) remain unclear. Thus, the management options and the progression-free survival (PFS) and the overall survival (OS) of EGFR-mutated NSCLC patients with solitary BM were investigated in the study. METHODS: We retrospectively reviewed the clinical data from NSCLC patients who harbored EGFR mutations and who presented solitary BM at diagnosis in our institute between 2012 and 2014. PFS and OS were evaluated using Kaplan-Meier methods and compared using log-rank tests. RESULTS: In total, 36 NSCLC patients with solitary BM who harbored EGFR mutations were enrolled in this study. The PFS and OS of these patients was 12.4 and 19.3 months, respectively. Sixteen patients underwent surgical resection of brain and lung lesions followed by EGFR-TKIs treatment, and the median OS was 28.0 months, which was significantly longer than 16.4 months of 14 patients received radiotherapy combined with or followed by EGFR-tyrosine kinase inhibitors (TKIs) and 15.8 months of 6 patients received radiotherapy followed by chemotherapy. The median PFS also showed the same trend in each group (16.1, 10.4, and 9.8 months, respectively). CONCLUSIONS: The survival was extended in the patients receiving surgical resection of brain and lung lesions followed by EGFR-TKIs treatment, and surgery combined with EGFR-TKIs could be a recommended treatment for EGFR mutated NSCLC patients with solitary BM.

Kidney bioengineering in regenerative medicine: An emerging therapy for kidney disease.

The prevalence of end-stage renal disease is emerging as a serious worldwide public health problem because of the shortage of donor organs and the need to take lifelong immunosuppressive medication in patients who receive a transplanted kidney. Recently, tissue bioengineering of decellularization and recellularization scaffolds has emerged as a novel strategy for organ regeneration, and we review the critical technologies supporting these methods. We present a summary of factors associated with experimental protocols that may shed light on the future development of kidney bioengineering and we discuss the cell sources and bioreactor techniques applied to the recellularization process. Finally, we review some artificial renal engineering technologies and their future prospects, such as kidney on a chip and the application of three-dimensional and four-dimensional printing in kidney tissue engineering.