Efficacy and Safety of 125I Seed Implantation in the Treatment of Pelvic Recurrent Cervical Cancer Following Radiotherapy: A Single-Arm Meta-Analysis of Chinese Patients.

BACKGROUND: The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. RECENT FIDINGS: The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. CONCLUSION: In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. TRIAL REGISTRATION: PROSPERO: CRD42023423857.

Transcriptomic and proteomic strategies to reveal the mechanism of Gymnocypris przewalskii scale development.

BACKGROUND: Fish scales are typical products of biomineralization and play an important role in the adaptation of fish to their environment. The Gymnocypris przewalskii scales are highly specialized, with scales embedded in only specific parts of the dermis, such as the areas around the anal fin and branchiostegite, making G. przewalskii an ideal material for biomineralization research. In this study, we aimed to unveil genes and pathways controlling scale formation through an integrated analysis of both transcriptome and proteome, of which G. przewalskii tissues of the dorsal skin (no scales) and the rump side skin (with scales) were sequenced. The sequencing results were further combined with cellular experiments to clarify the relationship between genes and signaling pathways. RESULTS: The results indicated the following: (1) a total of 4,904 differentially expressed genes were screened out, including 3,294 upregulated genes and 1,610 downregulated genes (with a filtering threshold of |log2Fold-Change|> 1 and p-adjust < 0.05). The identified differentially expressed genes contained family members such as FGF, EDAR, Wnt10, and bmp. (2) A total of 535 differentially expressed proteins (DEPs) were filtered out from the proteome, with 204 DEPs downregulated and 331 DEPs upregulated (with a filtering threshold of |Fold-Change|> 1.5 and p < 0.05). (3) Integrated analyses of transcriptome and proteome revealed that emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were important genes contributing to scale development and that PI3K-AKT was the most important signaling pathway involved. (4) With the use of the constructed G. przewalskii fibroblast cell line, emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were confirmed to be positively regulated by the PI3K-AKT signaling pathway. CONCLUSION: This study provides experimental evidence for PI3K-AKT controlled scale development in G. przewalskii and would benefit further study on stress adaptation, scale biomineralization, and the development of skin appendages.

Thermobacterium salinum gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from a hydrothermal zone.

A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain, designated as strain TK19130T, was isolated from the Lonqi hydrothermal zone in the Southwest Indian Ridge. Growth occurred with 1-12 % (w/v) NaCl (optimum, 2-4 %), at 10-40 °C (optimum, 30-35 °C) and at pH 6.0-9.0 (optimum, pH 7.0-8.0). The genome of strain TK19130T was 3.15 Mb, with a DNA G+C content of 41.35 %. Based on the results of 16S rRNA gene sequence analysis, strain TK19130T was affiliated with the family Flavobacteriaceae, in which the highest similarity was 90.54 % to Aureisphaera salina A6D-50T, under the genus demarcation boundary (94.50 %). Average nucleotide identity values between strain TK19130T and adjacent strains were 67.17-72.00 %, lower than the recommended threshold of 73.98 % for genus delineation. The predominant respiratory quinone of strain TK19130T was menaquinone 6. Major polar lipids were phosphatidylethanolamine, three aminolipids and one unidentified polar lipid. Major fatty acids were detected as iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. Based on the polyphasic taxonomic evidence presented above, strain TK19130T formed an independent branch representing a new species of a novel genus within the family Flavobacteriaceae, for which the name Thermobacterium salinum gen. nov., sp. nov. is proposed. The type strain is TK19130T (=CGMCC 1.18993T=JCM 35842T=MCCC M28200T).

Radiotherapy dosimetry and radiotherapy related complications of immediate implant-based reconstruction after breast cancer surgery.

Backgrounds: The impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR. Methods: We retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data. Results: IBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P<0.05). IBBR group also had lower radiotherapy dosimetric parameters in the ipsilateral lung and the heart of left breast cancer patients. The differences in the rates of radiation pneumonia (RP) and radiation dermatitis (RD) between the two groups were not statistically significant (P > 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05). Conclusion: Patients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy.

Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib.

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.

Prevalence and associated factors of inappropriate hospital admissions and days of children in a secondary hospital in Shanghai, China.

BACKGROUND: Although the appropriateness of hospital utilization of adults and the elderly in China was audited by several studies, the appropriateness of hospital use by children in Shanghai remains to be determined. This study aims to assess the level of inappropriate hospital admissions and hospital days, to detect factors associated with inappropriateness, and to elucidate reasons for inappropriateness. METHODS: A retrospective review of the records of 291 admissions and 1449 hospital days of children inpatients from a secondary hospital in Shanghai was performed by two reviewers using the Chinese version Pediatric Appropriateness Evaluation Protocol (C-PAEP). Demographics, socio-economic characteristics, and other admission- or hospital stay-related information were collected and analyzed to determine factors associated with inappropriateness utilizing multivariate regression models. RESULTS: 38.5% (n = 112) of admissions and 9.5% (n = 137) of hospital days were categorized as inappropriate, according to the C-PAEP. Children who were non-Shanghai residents (p < 0.001), admitted through the emergency sector (p = 0.030), and/or received services in a surgical ward (p < 0.001) had a higher risk of being admitted inappropriately. Payment method (p = 0.006), service type (p < 0.001), comorbidity (p = 0.016), length of stay (p = 0.007), and appropriateness of admission (p < 0.001) were found to be associated with prevalence of inappropriate hospital days. Approximately three-fourths of the inappropriate admissions were premature admissions (75.9%, n = 85). The most frequent reasons for inappropriate hospital days were awaiting test results (34.3%, n = 47), awaiting surgery (19.7%, n = 27), awaiting test execution (10.9%, n = 15), and family unprepared for home care (10.9%, n = 15). CONCLUSIONS: Although the extent of inappropriate hospital days was moderate compared with that found by previous investigations, the prevalence of inappropriateness of admission was considerable. To enhance the appropriateness of hospital care for children, interventions could be implemented according to the associated factors and identified causes.

Identification of novel biomarkers in breast cancer via integrated bioinformatics analysis and experimental validation.

Breast cancer (BC), an extremely aggressive malignant tumor, causes a large number of deaths worldwide. In this study, we pooled profile datasets from three cohorts to illuminate the underlying key genes and pathways of BC. Expression profiles GSE42568, GSE45827, and GSE124646, including 244 BC tissues and 28 normal breast tissues, were integrated and analyzed. Differentially expressed genes (DEGs) were screened out based on these three datasets. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plugin were utilized to visualize protein protein interaction (PPI) of these DEGs. The module with the highest connectivity of gene interactions was selected for further analysis. All of these hub genes had a significantly worse prognosis in BC by survival analysis. Additionally, four genes (CDK1, CDC20, AURKA, and MCM4) dramatically were enriched in oocyte meiosis and cell cycle pathways through re-analysis of DAVID. Moreover, the mRNA and protein levels of CDK1, CDC20, AURKA, and MCM4 were significantly increased in BC patients. In addition, knockdown of CDK1 and CDC20 by small interfering RNA remarkably suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. In conclusion, our results suggested that CDK1, CDC20, AURKA, and MCM4 were reliable biomarkers of BC via bioinformatics analysis and experimental validation and may act as prospective targets for BC diagnosis and treatment.

Highly Enhancing Electrical, Thermal, and Mechanical Properties of Polypropylene/Graphite Intercalation Compound Composites by In Situ Expansion during Melt Mixing.

Polypropylene/graphite intercalation compound (PP/GIC) composites are prepared via melt mixing at three different temperatures (180, 200, and 220 °C). The dispersion of GICs in the composites is clearly improved due to the increased interlamellar spacing caused by in situ expansion of GICs at higher temperatures, which facilitates the intercalation of PP molecular chains into the GIC galleries. As a result, the PP/GIC composite with 10 wt% GICs prepared at 220 °C (PG220) presents a dielectric constant of about 1.3 × 108 at 103 Hz, which is about six orders higher than that of the composite prepared at 180 °C (PG180). Moreover, the thermal conductivity of the PG220 sample (0.63 Wm-1K-1) is 61.5% higher than that of the PG180 sample. The well-dispersed GICs accelerates the crystallization of PP by increasing the nucleation point and enhances the thermal stability of the composites. The PG220 sample shows a Young's modulus that is about 21.2% higher than that of the PG180 samples. The results provide an efficient approach for fabricating polymer/GIC composites without complex exfoliation and dispersion processes.

Baicalein modulates the radiosensitivity of cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway.

BACKGROUND: Increasing radiosensitivity of cancer cells can enhance the efficacy of cervical cancer treatment. OBJECTIVES: This study evaluated the potential roles and mechanism of baicalein in regulating the radiosensitivity of cervical cancer cells in vitro. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess miR-183 expression in End1/E6E7 cells, Hela cells and Hela cells irradiated with X-ray (0 Gy, 1 Gy, 3 Gy, 5 Gy, and 10 Gy). Cell Counting Kit-8 (CCK-8) method measured cell viability of Hela cells after miR-183 regulation, baicalein or RO8191 treatment. Apoptosis rates were detected using flow cytometry. Thereafter, expression of Bcl-2, Bax and caspase-3 RNA was also detected through RT-qPCR. Protein concentrations of E-cadherin, N-cadherin, Vimentin in epithelial-mesenchymal transition (EMT), phospho-JAK2/STAT3, and total Janus kinase 2/signal transducer and activator of transcription 3 STAT3 (JAK2/STAT3) were examined using enzyme-linked immunosorbent assay (ELISA) methods. RO8191, a JAK2/STAT3 activator, was used to activate the JAK2/STAT3 signaling pathway. RESULTS: The miR-183 expression was significantly lower in Hela cells compared to End1/E6E7 cells. Following upregulation of miR-183 in Hela cells, cell viability was inhibited while apoptosis was promoted. Moreover, EMT was inhibited after miR-183 over-expression. X-ray treatment markedly reduced the cell survival rate and increased miR-183 RNA expression. Baicalein treatment severely reduced the cell viability of 10-Gy X-ray-irradiated Hela cells, partially reversing the effect of miR-183, and also increased apoptosis and prevented EMT in irradiated cells. Y1007/8 in JAK2 and tyrosine (Tyr) residue 705 of STAT3 were phosphorylated, resulting in high expression of JAK2/STAT3, which was decreased by irradiation and baicalein treatment. RO8191 activated JAK2/STAT3 signaling, promoted cell viability and EMT, and inhibited cell apoptosis, while baicalein partly reversed the functions of RO8191. CONCLUSIONS: Baicalein inhibited cell viability and EMT, and induced cell apoptosis of Hela cells, through upregulating miR-183 via inactivation of the JAK2/STAT3 signaling pathway.

Safety and efficacy of 3D-printed templates assisted CT-guided radioactive iodine-125 seed implantation for the treatment of recurrent cervical carcinoma after external beam radiotherapy.

OBJECTIVE: To investigate the safety and efficacy of 3-dimensional (3D) printing non-coplanar templates (PNCT) assisted computer tomography (CT) guided radioactive 125I seed implantation (RISI) for the treatment of recurrent cervical carcinoma (RCC) after external beam radiotherapy (EBRT). METHODS: A total of 103 patients with inoperable post-EBRT RCC were included in this retrospective study. A total of 111 lesions received RISI. Eight lesions were at the pelvic center, 75 lesions were at the pelvic lateral, and 28 lesions were extra-pelvic metastasis. The median prescription dose was 120 Gy. The primary end points were adverse events and local control (LC), and the secondary end points were overall survival (OS) and progression-free survival. RESULTS: Grade 2 adverse events of acute nausea, diarrhea, and pollakiuria occurred in 1, 2, and 1 patient, respectively. One patient suffered from grade 3 acute proctitis. Late toxicity was observed in 2 patients with rectovaginal fistula. No grade 5 toxicity occurred. The 3-year LC and OS rates were 75.1% and 20.8%, respectively. The median OS was 17 months. The multivariate analysis showed that the minimum dose received by the "hottest" 90% of the gross tumor volume (D90) ≥130 Gy, squamous cell carcinoma, hemoglobin ≥80 g/L and good short-term efficacy (complete response or partial response) were independent predictors of LC and OS (all p<0.05). CONCLUSIONS: 3D-PNCT assisted CT-guided RISI is a safe, effective, and minimally invasive modality for RCC. The hemoglobin level, pathological type, dose distribution and short-term efficacy are considered as independent factors for clinical outcomes.

Association Between 17-ß-Estradiol and Interleukin-8 and Visual Field Progression in Postmenopausal Women with Primary Angle Closure Glaucoma.

PURPOSE: To investigate an association between sex hormones and inflammatory cytokines, and to determine whether baseline 17-ß-estradiol (E2) and interleukin-8 (IL-8) are associated with visual field (VF) progression in postmenopausal women with primary angle closure glaucoma (PACG). DESIGN: A prospective cross-sectional and cohort study. PARTICIPANTS: The cross-sectional study enrolled 200 postmenopausal women with PACG and 151 healthy postmenopausal women as normal control subjects. A total of 105 postmenopausal women with PACG were included and followed up for ≥2 years in the cohort study. METHODS: All participants were evaluated for levels of baseline sex hormones (follicle-stimulating hormone, prolactin, progesterone, testosterone, luteinizing hormone, and E2) and inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-10, and C-reactive protein) and underwent VF examinations. The cross-sectional study was conducted to establish risk factors for postmenopausal women with PACG using logistic regression analysis. The cohort study was designed to identify factors that could be used to predict VF progression in postmenopausal women with PACG using multivariate Cox regression analyses. The main outcome measures included factors associated with VF progression over time. RESULTS: Decreased E2 (odds ratio 0.88 [95% confidence interval {CI} 0.78-0.99], P = .007) and increased IL-8 (odds ratio 1.12 [95% CI 1.01-1.23], P < .001) levels were risk factors in postmenopausal women with PACG. A significant negative correlation was observed between IL-8 levels and E2 (r = -0.21, P = .02). Multivariable regression analyses revealed a significant correlation between E2 levels and visual field mean deviation (MD) (B = -0.16, P = .04 [95% CI -.09 to -.003) and between IL-8 levels and MD (B = 0.36, P < .001 [95% CI 0.01-0.02]). During follow-up, 48 (45.71%) patients showed VF progression. Lower baseline E2 (hazard ratio 0.85 [95% CI 0.82-0.88], P = .04) and higher baseline IL-8 levels (hazard ratio 1.01 [95% CI 1.00-1.02], P = .004) were associated with progression of glaucoma. Patients with lower E2 levels had a significantly higher rate of PACG progression (log-rank test P < .001), similar to those with higher IL-8 levels (log-rank test P = .04). CONCLUSIONS: Decreased E2 and increased IL-8 levels at baseline are significant predictors of VF progression in postmenopausal women with PACG.

Extent and cost of inappropriate use of tumour markers in patients with pulmonary disease: a multicentre retrospective study in Shanghai, China.

OBJECTIVES: The currently implemented healthcare reform in China requires substantial capital investment. Although overtreatment results in serious waste, inappropriate laboratory use is widespread, and overuse of tumour markers (TMs) has attracted increasing attention. DESIGN: Retrospective study. SETTING: The respiratory, thoracic surgery and oncology departments of three hospitals in Shanghai from 2014 to 2015. PARTICIPANTS: Patients with chronic obstructive pulmonary disease (COPD) and primary bronchogenic lung cancer (PLC). Based on clinical guidelines and physician experience, the criteria of suitability of TM examinations were determined, and the number, cost and proportion of inappropriate TM requests were analysed. RESULTS: The area under the receiver operating characteristic curve for carcinoembryonic antigen+cytokeratin fragment 21-1+squamous cell carcinoma antigen+neuron-specific enolase in patients with COPD and PLC was 0.813, in accordance with the cost-effectiveness principle, indicating good clinical and health economics values. In the 2706 patients, 12 496-16 956 (58.27%-79.06%) of TM requests were inappropriate. Furthermore, the involved expense was 650 200-1 014 156 yuan, accounting for 7.69%-12.00% of examination expenses and 1.35%-2.11% of hospitalisation costs. CONCLUSIONS: We found that the inappropriate use of TMs was widespread for patients with pulmonary disease. Clinicians should use TMs strictly according to the guidelines to effectively manage laboratory resources and control costs.

miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT.

MicroRNAs (miRNAs) are a class of endogenous, evolutionarily conserved small non-coding RNA molecules that mediate the posttranscriptional process of target gene, leading to translational repression or degradation of target mRNAs. A series of studies have indicated that miRNAs play an important role in tumor initiation, development and progression. In this study, we found that down regulation of miR-598 was a frequent event in CRC tissues compared to the paracarcinoma tissues. And the study demonstrated that miR-598 was implicated in CRC metastasis. Transwell migration assay revealed that elevated miR-598 expression reduces CRC cell migration. Moreover, our study showed that suppression of miR-598 expression induces CRC cell epithelialmesenchymal transition(EMT) and overexpression of miR-598 inhibits CRC cell EMT. In addition, bioinformatics target prediction identified JAG1 as a putative target of miR-598. Knockdown of miR-598 was shown to upregulate JAG1 expression. Furthermore, overexpression of miR-598 suppressed the expression of JAG1. Consistent results were also obtained when the regulation of JAG1 expression by miR-598 was further specified in CRC tissues. Moreover, overexpression of JAG1 induces epithelialmesenchymal transition(EMT) and promotes the metastasis of CRC cells. Decreased Notch2 expression suppresses CRC cells metastasis and EMT. Together, these results indicate that miR-598 is a novel regulator of colorectal cancer metastasis. Our data suggest miR-598 is implicated in regulating Epithelial-mesenchymal transitions by directly suppressing its downstream target gene JAG1 to inactivate Notch signaling pathway.

[Outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy].

OBJECTIVE: To evaluate the outcomes and prognostic factors of distant metastasis in patients with advanced cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). METHODS: A total of 118 patients with International Federation of Gynecology and Obstetrics (FIGO, 2009 version) stage II b-IVa cervical squamous cell carcinoma treated with CCRT between 2006 and 2010 in the Second Affiliated Hospital of Dalian Medical University were analyzed. Their median age was 48 years (range, 23-70 years). FIGO stages were as follows: IIb stage 56 cases, IIIa stage 6 cases, IIIb stage 52 cases, and IVa stage 4 cases. Of the all patients, 55 cases showed bulkly tumor (tumor size >4 cm) and 35 cases were pelvic lymph node positive. Forty patients had pretreatment hemoglobin (Hb) levels no greater than 110 g/L. Patients with elevated squamous cell carcinoma antigen (SCC- Ag) >1.5 µg/L before CCRT and at one month after CCRT were 91 cases and 34 cases, respectively. Kaplan-Meier method was used to estimate survival. For the analysis of prognostic factors affecting distant metastasis, log- rank test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. RESULTS: Thirty- seven patients were diagnosed with recurrence, 19 cases of whom developed distant metastasis, 13 cases developed loco-regional recurrence and 5 cases had both distant and loco-regional recurrence. The 5- year overall survival rates and distant disease- free survival of all patients were 64.0% and 78.8% , respectively. Two patients had grade 3 acute gastrointestinal toxicity (mainly diarrhea) and 20 cases had grade 3 to 4 hematologic toxicity. Seven patients experienced grade 3 to 4 late toxicity, 5 cases of them were gastrointestinal and 2 cases were genitourinary toxicity. Univariate analysis showed that FIGO stages, SCC-Ag level at one month after treatment, pretreatment hemoglobin level, and pelvic lymph node metastasis were significantly correlated with distant metastasis (all P < 0.05). Multivariate analysis showed that FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis were independent prognostic factors for distant metastasis (all P < 0.05). CONCLUSIONS: For stage IIb-IVa cervical squamous cell carcinoma, the regimen of CCRT was efficacious and safe. The predictive factors for distant metastasis in patients with IIb-IVa stage squamous cell carcinoma of cervix treated with CCRT included FIGO stage, SCC- Ag level at one month after treatment, and pelvic lymph node metastasis. New treatment strategies should be considered to control distant metastasis for these patients.

BioXpress: an integrated RNA-seq-derived gene expression database for pan-cancer analysis.

BioXpress is a gene expression and cancer association database in which the expression levels are mapped to genes using RNA-seq data obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, Expression Atlas and publications. The BioXpress database includes expression data from 64 cancer types, 6361 patients and 17 469 genes with 9513 of the genes displaying differential expression between tumor and normal samples. In addition to data directly retrieved from RNA-seq data repositories, manual biocuration of publications supplements the available cancer association annotations in the database. All cancer types are mapped to Disease Ontology terms to facilitate a uniform pan-cancer analysis. The BioXpress database is easily searched using HUGO Gene Nomenclature Committee gene symbol, UniProtKB/RefSeq accession or, alternatively, can be queried by cancer type with specified significance filters. This interface along with availability of pre-computed downloadable files containing differentially expressed genes in multiple cancers enables straightforward retrieval and display of a broad set of cancer-related genes.

Human germline and pan-cancer variomes and their distinct functional profiles.

Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 549 variations that significantly affect 10 major functional sites. Furthermore, we found distinct patterns of site disruptions due to germline and somatic nsSNVs. Pan-cancer analysis across 12 different cancer types led to the identification of 51 genes with 106 nsSNV affected functional sites found in 3 or more cancer types. 13 of the 51 genes overlap with previously identified Significantly Mutated Genes (Nature. 2013 Oct 17;502(7471)). 62 mutations in these 13 genes affecting functional sites such as DNA, ATP binding and various PTM sites occur across several cancers and can be prioritized for additional validation and investigations.

Curcumin protects mice from coxsackievirus B3-induced myocarditis by inhibiting the phosphatidylinositol 3 kinase/Akt/nuclear factor-κB pathway.

Viral myocarditis is an inflammation of the myocardium, and coxsackievirus B3 (CVB3) is one of the most important etiologic agents. Curcumin is an active ingredient of Curcumin longa, which has been used as a traditional Chinese herb for the treatment of various inflammatory diseases. The aim of this study was to explore the therapeutic effect of curcumin on CVB3-induced myocarditis and the underlying mechanism. Our results showed that treatment with curcumin could significantly attenuate CVB3-induced myocarditis, as demonstrated by improved weight loss, increased survival rate, reduced serological level cardiac enzymes, and improved heart histopathology. Of importance, curcumin administration was revealed to significantly reduce the systemic and local myocardial expression of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL) 6, and IL-1ß, in the CVB3-infected mice. Further study showed that curcumin treatment significantly inhibited the CVB3-induced activation of nuclear factor-κB (NF-κB), a key transcription factor in the pathogenesis of inflammation, in a phosphatidylinositol 3 kinase (PI3K)/Akt pathway-dependent manner. These data indicate that curcumin has protective effect against CVB3-induced myocarditis by inhibiting PI3K/Akt/NF-κB signaling pathway and thus reducing the inflammatory response.

Progress and prospects in stem cell therapy.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

Glycyrrhizin administration ameliorates coxsackievirus B3-induced myocarditis in mice.

In this study, the authors explored the therapeutic effect of glycyrrhizin (GL) on Coxsackievirus B3 (CVB3)-induced myocarditis and its possible mechanisms involved. The results of this study showed that GL exhibited a profound amelioration of CVB3-induced myocarditis, as evidenced by improved weight loss profile, less increased serological levels of cardiac enzymes, less myocardial inflammation and increased survival rate. Further study showed that this effect was not due to the viral clearance but ascribed to weakened proinflammatory responses, as evidenced by significantly reduced expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß and interleukin-6. Moreover, the authors demonstrated that GL administration inhibited CVB3-induced nuclear factor-κB activity efficiently by blocking the degradation of nuclear factor -κB inhibitor IκBκ. These data suggest that GL can effectively attenuate the severity of CVB3-induced myocarditis and may present as a new therapeutic approach for the treatment of viral myocarditis.