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BACKGROUND: The unilateral biportal endoscopic (UBE) technique has been widely used in spine surgery. At present, a traditional rigid working channel is available for the UBE system. A metal semicircular canal is located in the working channel. However, due to the metal material of the working channel, arthroscopy and instruments are constrained from moving in UBE surgery. Additionally, an assistant is needed during the procedure to hold the traditional working channel. OBJECTIVE: For simplicity of operation and convenient movement of the arthroscopy and instrument, we describe a new method for establishing operative channels in UBE surgery. METHODS: We retrospectively reviewed 50 patients who underwent unilateral biportal endoscopic discectomy (UBED) from February 2020 to August 2020 via our new method. The Oswestry Disability Index (ODI) and visual analogue scale (VAS) score were measured preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Statistical comparisons were made using analysis of covariance and paired t tests. RESULTS: The VAS scores for back pain at the five time points were 5.20 ± 2.57, 1.96 ± 0.95, 1.50 ± 0.84, 1.64 ± 1.08 and 1.18 ± 0.39. The leg pain VAS scores were 7.02 ± 2.25, 2.02 ± 1.27, 1.48 ± 0.89, 1.32 ± 0.79 and 0.88 ± 0.52. The ODI values were 51.08 ± 19.97, 19.62 ± 15.51, 8.26 ± 7.40, and 7.54 ± 6.42 to 3.24 ± 1.10. The postoperative ODIs and VAS scores of low back pain and leg pain were significantly lower than those before surgery, and differences were statistically significant (all p< 0.05). The pressure of the closed outflow was significantly higher than that of the open outflow (37.35 ± 13.11 mm Hg vs. 24.55 ± 12.64 mm Hg p= 0.003). After we tightened the infusion strap to open the outflow, the pressure decreased significantly (26.4 ± 14.08 mm Hg vs. 37.35 ± 13.11 mm Hg p= 0.015). There were 2 cases of complications, including 1 case of postoperative recurrence and 1 case of dural tears. CONCLUSION: This study demonstrates the technical feasibility, safety, and efficacy of modified channel establishment in UBE surgery.

International sport has always been associated with nationalism. The purpose of the study was to explore how Chinese media and the general public perceived the doping scandal of their national sports hero, Sun Yang. Through analyzing 11 Chinese media outlets’ coverage on Chinese social media Weibo, the results revealed that Chinese media covered Sun and his team’s reaction and perspectives on this issue more when compared with other news. The general public’s perceptions toward this scandal tended to be favorable toward Sun, with 55.5% of selected Weibo comments defending Sun after his 8-year ban for doping was handed down. The analysis of these social media comments posted by sports fans showed that the general public’s perceptions might have been impacted by their nationalism, international relations, and media coverage. In addition, the study revealed the Chinese public’s perceptions toward current antidoping regulations.

Clear party political culture concept is a scientific understanding of the communist party of China party politics culture construction rule and the precondition of constructing party political culture system. Since xi general secretary on the sixth plenary session of 18 first proposed "the party's political culture" in this era proposition, domestic academia on its relevant concepts "launched a multi-angle and deep worth research and the elaboration, has achieved rich results. At the same time should also be aware of, because "the party's political culture" in this era proposition put forward by the time is short, scholars for the study of the concept of "political culture" party is still in its infancy, there are the core concepts definition is not clear, the research Angle of view of a single, lack of comparative study and deficiency, so need to be promoted from the three aspects.

Skin is a complex ecosystem colonized by millions of microorganisms, including bacteria, fungi, and viruses. Skin microbiota is believed to exert critical functions in maintaining host skin health. Profiling the structure of skin microbial community is the first step to overview the ecosystem. However, the community composition is highly individualized and extremely complex. To explore the fundamental factors driving the complexity of the ecosystem, namely the selection pressures, we review the present studies on skin microbiome from the perspectives of ecology. This review summarizes the following: (1) the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment, highlighting their proposed function on skin microbiota; (2) the features of dominant skin commensals to occupy ecological niches, through self-adaptation and microbe–microbe interactions; (3) how skin microbes, by their structures or bioactive molecules, reshape host skin phenotypes, including skin immunity, maintenance of skin physiology such as pH and hydration, ultraviolet (UV) protection, odor production, and wound healing. This review aims to re-examine the host–microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.

Lead halide perovskite nanocrystals (PNCs) have emerged as new-generation light-emitting materials with important potentials in optoelectronic applications. However, the toxicity of lead metal and ...

Background: Current identification of chronic myelogenous leukemia markers tends to mine diagnostic or prognostic biomarkers, ignoring susceptibility markers in normal samples. Objective: We aim to identify possible susceptibility markers for preventing chronic myelogenous leukemia. Methods: Functional links of H3K79me2 patterns and gene expression changes were inferred by correlation analyses. DNase-seq read distribution, transcription factor motifs, and their binding data were acquired via ceasBW and HOMER. Normalized transcription factor binding signals were submitted to a random forest algorithm to predict susceptibility gene expression changes. Three strategies were performed to validate the influence of low H3K79me2 signals on gene expression changes. Results: The gene-body H3K79me2 signals in normal samples were negatively related to gene expression changes during leukemogenesis (ρ=-0.92), regardless of gene lengths and expression levels. Characterization revealed that genes with lower H3K79me2 signals in normal samples have more open environments. Transcription factors GATA3, GATA4, TEAD1, TEAD3, TEAD4, and TRPS1 may induce the upregulation of up-susceptibility genes (ρ=0.95), and ASCL2, IRF4, IRF3, E2A, OCT4, and ZEB2 may mediate the downregulation of down-susceptibility genes (ρ=0.97). Enrichment analysis implied that the screened susceptibility genes were involved in leukemia-related pathways, and about 50% of leukemia stem cell differentially expressed genes were included in these genes. Besides, all hub genes extracted from susceptibility genes were well documented in different leukemia subtypes. Finally, the effect of H3K79me2 signals on gene expression changes were validated in a mouse model and three cell models. Conclusion: Low gene-body H3K79me2 signals in normal samples may serve as susceptibility markers for chronic myelogenous leukemia.

Background: Epithelial-Mesenchymal Transition (EMT) and its reverse Mesenchymal- Epithelial Transition (MET) are essential for tumor cells metastasis. However, the effect of epigenetic modifications on this transition is unclear. Objective: We aimed to explore the key histone modifications and hub genes of EMT/MET during Colorectal Cancer (CRC) metastasis. Method: The differentially expressed genes and differentially histone modified genes were identified. Based on the histone modification features, the up- and down-regulated genes were predicted by Random Forest algorithm. Through protein-protein interaction network and Cytoscape analysis, the hub genes with histone modification changes were selected. GO, KEGG and survival analyses were performed to confirm the importance of the hub genes. Results: It was found that H3K79me3 plays an important role in EMT/MET. And the 200-300bp and 400-500bp downstream of TSS may be the key regulatory regions of H3K79me3. Moreover, we found that the expression of the hub genes was down-regulated in EMT and then up-regulated in MET. And the changes of the hub genes expression were consistent with the changes of H3K79me3 signal in the specific regions of the genome. Finally, the hub genes KRT8 and KRT18 were involved in the metastasis process and were significantly related to the survival time. Conclusion: H3K79me3 may be crucial for EMT/MET, and the hub genes KRT8 and KRT18 may be the key genes in this process.

Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm in precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases in vivo has limited their utility. Here we exploit chemically stabilized nucleic acids to multiplex synthetic biomarkers and produce diagnostic signals in biofluids that can be ‘read out’ via CRISPR nucleases. The strategy relies on microenvironmental endopeptidase to trigger the release of nucleic acid barcodes and polymerase-amplification-free, CRISPR-Cas-mediated barcode detection in unprocessed urine. Our data suggest that DNA-encoded nanosensors can non-invasively detect and differentiate disease states in transplanted and autochthonous murine cancer models. We also demonstrate that CRISPR-Cas amplification can be harnessed to convert the readout to a point-of-care paper diagnostic tool. Finally, we employ a microfluidic platform for densely multiplexed, CRISPR-mediated DNA barcode readout that can potentially evaluate complex human diseases rapidly and guide therapeutic decisions.

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Purpose: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival.Experimental Design: We searched PubMed and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS).Results: From 1,201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and noncarriers in patients with ovarian or breast cancer. Fourteen studies examined ovarian cancer survival and 13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2 mutation carriers had better OS (HR, 0.76; 95% CI, 0.70–0.83 for BRCA1 mutation carriers; HR, 0.58; 95% CI, 0.50–0.66 for BRCA2 mutation carriers) and PFS (HR, 0.65; 95% CI, 0.52–0.81 for BRCA1 mutation carriers; HR, 0.61; 95% CI, 0.47–0.80 for BRCA2 mutation carriers) than noncarriers, regardless of tumor stage, grade, or histologic subtype. Among patients with breast cancer, BRCA1 mutation carriers had worse OS (HR, 1.50; 95% CI, 1.11–2.04) than noncarriers but were not significantly different from noncarriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis.Conclusions: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancers and these mutations should be taken into account when devising appropriate therapeutic strategies. Clin Cancer Res; 21(1); 211–20. ©2014 AACR.

Complete Supplementary Information for the manuscript, including Supplemental Figures 1-16 and tables 1-4.

Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due to a lack of methods to measure and localize protease activity directly within the tissue microenvironment, the design of protease-activated agents has been necessarily empirical, yielding suboptimal results when translated to patients. To address the need for spatially resolved protease activity profiling in cancer, we developed a new class of in situ probes that can be applied to fresh-frozen tissue sections in a manner analogous to immunofluorescence staining. These activatable zymography probes (AZP) detected dysregulated protease activity in human prostate cancer biopsy samples, enabling disease classification. AZPs were leveraged within a generalizable framework to design conditional cancer diagnostics and therapeutics and showcased in the Hi-Myc mouse model of prostate cancer, which models features of early pathogenesis. Multiplexed screening against barcoded substrates yielded a peptide, S16, that was robustly and specifically cleaved by tumor-associated metalloproteinases in the Hi-Myc model. In situ labeling with an AZP incorporating S16 revealed a potential role of metalloproteinase dysregulation in proliferative, premalignant Hi-Myc prostatic glands. Systemic administration of an in vivo imaging probe incorporating S16 perfectly classified diseased and healthy prostates, supporting the relevance of ex vivo activity assays to in vivo translation. We envision AZPs will enable new insights into the biology of protease dysregulation in cancer and accelerate the development of conditional diagnostics and therapeutics for multiple cancer types.Significance:Visualization of protease activity within the native tissue context using AZPs provides new biological insights into protease dysregulation in cancer and guides the design of conditional diagnostics and therapeutics.

Supplementary Tables S1 and S2. Table S1. Clinical characteristics of the included studies for ovarian cancer. Table S2. Clinical characteristics of the included studies for breast cancer.

Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC.Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC.Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro. In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1–positive HNC samples than in negative samples.Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659–73. ©2017 AACR.

charateritics of 84 HNSCC patients

Supplementary Figure S1. Funnel plots of the meta-analyses assessing the associations between BRCA mutations and survival. (A) Studies about effect of BRCA1 mutation on ovarian cancer OS, (B) Studies about effect of BRCA2 mutation on ovarian cancer OS, (C) Studies about effect of BRCA1 mutation on breast cancer OS, (D) Studies about effect of BRCA1 mutation on breast cancer PFS.

S1. Identification of RARS-MAD1L1 by RNA-Seq. S2. RARS-MAD1L1 promotes the proliferation and colony-formation ability of p53-/- MEFs and S26 cells. S3. RARS-MAD1L1 enhances CSC properties in NPC cells. S4. Knockdown of endogenous RARS-MAD1L1 reduces the CSC characteristics of C666-1 cells. S5. Knockdown of RARS-MAD1L1 reduces the oncogenic function of S26 cells induced by RARS-MAD1L1. S6. RARS-MAD1L1 overexpression presents a stronger oncogenic function than wild-type RARS in NPC cells. S7. Knockdown of c-Myc reduces the expression of ABCG2 S8. Schematic illustration of the mechanism through which RARS-MAD1L1 induces cancer stem cell properties and therapeutic resistance through the FBP1/c-Myc axis.

Supplemental Methods and Materials

RARS-MAD1L1 gDNA fusion sequence by Sanger Sequencing

RARS-MAD1L1 sequence

Epstein-Barr virus (EBV) immortalization of resting B lymphocytes (RBLs) to lymphoblastoid cell lines (LCLs) models human DNA tumor virus oncogenesis. RBL and LCL chromatin interaction maps are compared to identify the spatial and temporal genome architectural changes during EBV B cell transformation. EBV induces global genome reorganization where contact domains frequently merge or subdivide during transformation. Repressed B compartments in RBLs frequently switch to active A compartments in LCLs. LCLs gain 40% new contact domain boundaries. Newly gained LCL boundaries have strong CTCF binding at their borders while in RBLs, the same sites have much less CTCF binding. Some LCL CTCF sites also have EBV nuclear antigen (EBNA) leader protein EBNALP binding. LCLs have more local interactions than RBLs at LCL dependency factors and super-enhancer targets. RNA Pol II HiChIP and FISH of RBL and LCL further validate the Hi-C results. EBNA3A inactivation globally alters LCL genome interactions. EBNA3A inactivation reduces CTCF and RAD21 DNA binding. EBNA3C inactivation rewires the looping at the CDKN2A/B and AICDA loci. Disruption of a CTCF site at AICDA locus increases AICDA expression. These data suggest that EBV controls lymphocyte growth by globally reorganizing host genome architecture to facilitate the expression of key oncogenes.

BackgroundThis randomized controlled trial (RCT) aimed to compare two different routes of postoperative estrogen treatment on the improvements of menstruation, postoperative endometrial thickness, and fertility outcomes in patients with moderate to severe intrauterine adhesions (IUA).MethodsThis study prospectively included 78 women (age: 25 to 45 years) with moderate to severe IUA who underwent hysteroscopic resection of adhesions between March 2019 and October 2020. The enrolled patients were randomized 1:1 into either the transdermal gel group (n = 39) or the estradiol valerate oral tablet group (n = 39) on the day of receiving hysteroscopy. Postoperative endometrial thickness, AFS (American Fertility Society) score, estrogen level, and the pattern and amount of menstruation were compared. Pregnancy information was actively collected during 1-year follow-up after the operation.ResultsThe postoperative endometrium thickness was improved in both groups, and both groups gained menstruation improvement rates of 67%. For patients who underwent second-look hysteroscopy (17 from the oral group and 19 from the transdermal group), the mean AFS score declined greater than 2 in both groups. For patients with postoperative pregnancy intention, the pregnancy rates at 1-year follow-up after the procedures were 40.5% and 28% in the transdermal group and oral group, respectively. Although no statistically significant difference was observed between the two groups, patients in the transdermal group had a tendency toward increased pregnancy rate.ConclusionsTransdermal administration of estrogen is equally efficacious as oral estrogen in postoperative treatment of IUA patients with a relatively safe profile. It is very likely to broaden its indication to the field of IUA.Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=37197, identifier ChiCTR1900022110.

Background: Despite the complexity, distinct ecological niches are believed to primarily drive the skin microbiome composition. Meanwhile, skin aging is a dynamic process with a spectrum of phenotypical changes, making it an attractive model for studying microbiome-phenotype interactions. Although a large number of studies confirmed the impact of chronological age in skin bacterial communities, the understanding of cross-kingdom microbiome variation with skin aging remains minimal. And this is not trivial because one’s skin condition or perceived age may deviate largely from their actual age as skin aging is a complex process combining chronological and extrinsic aging. Results: To this end, 822 facial microbial samples and skin phenotypes from the corresponding area were assessed in a Chinese cohort, the largest population size to date for skin shotgun metagenomic profiling. Our data revealed that among 14 measured variables, porphyrin and chronological age explained the most significant microbial variability. Consistent with previous studies based on 16S rRNA gene sequencing, we revealed increased biodiversity with aging and further specified age-associated species across kingdoms. While the abundance of most bacteria increased with age, two species, Cutibacterium acnes and Aeromicrobium choanae, declined. Microbiome undergoes active function selection from energy demands/growth to stress adaptation along aging. In addition, we characterized microbial changes in skin aging, asa combined consequence of both intrinsic and extrinsic reasons and reflecting the actual dynamic of niche conditions rather than chronological age. Using the multiple linear regression model, we predicted premature-aging/delayed-aging-related microbial species, mainly localizing to Moraxella osloensis and C. acnes. Furthermore, we validated the biological functions in vitro of some host-microbe interactions predicted by the microbiome-skin phenome association network. M. osloensis regulated collagen metabolism, extracellular matrix assembly and promoted cell senescence in human keratinocyte and fibroblast cells. Conclusions: We presume that application of both culture-independent and culture-dependent approaches can advance a good understanding of microbiome-phenotype interactions. Our study is of significance for designing interventions against aging-related skin conditions.

Hepatocellular carcinoma (HCC) is a common cancer with high morbidity and mortality. As we all know, the alteration of DNA methylation has a crucial impact on the occurrence of HCC. However, the mechanism of the effect of DNA methylation in different regions on gene expression is still unclear. Here, by computing and analyzing the distribution of differential methylation in 12 different regions in HCC tissues and adjacent normal tissues, not only the hypermethylation of CpG islands and global hypomethylation were found, but also a stable distribution pattern of differential methylation in HCC was found. Then the correlations between DNA methylations in different regions and gene expressions were calculated, and the diversity of correlations in different regions was determined. The key genes of differential methylation and differential expression related to the survival of HCC patients were obtained by using Cox regression analysis, a four-gene prognostic risk scoring model was constructed, and the prognostic performance was well verified. The regions of the differentially methylated CpG sites corresponding to the four key genes were located and their influences on the expression were analyzed. The results indicate that the promoter, first exon, 5'UTR, sixth exon, N_Shore, and S_Shore hypomethylation promotes the expression of key oncogenes, which together lead to the occurrence of HCC. These results might help to study the role of DNA methylation in HCC and provide potential biomarkers for the diagnosis of HCC.

Chemotherapy offers long-term clinical benefits to many cancer patients. However, several pre-clinical studies have demonstrated that certain cytotoxic drugs enhance metastasis via multiple mechanisms. These studies have mainly focused on tumor cell-derived inflammation. The importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Here, we showed that multi-dose Gemcitabine (GEM) treatment promoted breast cancer lung metastasis in a transgenic spontaneous breast cancer animal model. Both CCR2+macrophages and monocytes were increased in the lungs of GEM-treated mice. Further, the increase of CCR2+macrophages and monocytes were observed in naïve (tumor-free) mice after GEM treatment. These changes were largely caused by chemotherapy-induced reactive myelopoiesis that are biased toward monocyte development. Mechanistically, enhanced production of mitochondrial ROS (mtROS) was observed in GEM-treated BM LSK cells and monocytes. Treatment with the mitochondrial targeted antioxidant abrogated GEM induced hyper differentiation of BM progenitors. In addition, GEM treatment induced up-regulation of host cell-derived CCL2, and CCL2/CCR2 axis played essential role in the pro-metastatic host response induced by chemotherapy. Further, GEM and Paclitaxel (PTX) in combination with Doxorubicin (DOX) treatment resulted in up-regulation of coagulation factor X (FX) in lung interstitial macrophages. Targeting activated FX (FXa) using FXa inhibitor or F10 gene knockdown reduced pro-metastatic effect of chemotherapy-triggered host response. Together, these studies suggest a novel mechanism for chemotherapy induced metastasis via the host response-induced accumulation of monocytes/macrophages and interplay between coagulation and inflammation in the lungs.

Purpose This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). Methods A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler’s formula was employed to estimate the patient’s blood volume (PBV), Gross’s formula to estimate TBL, and Sehat’s formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. Results TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. Conclusions Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.

LZTR1 is associated with several diseases, including liver cancer, childhood cancer, and schwannomas. However, LZTR1’s role in colon cancer and its mechanism of action have not been reported. The colon cancer tissues and adjacent tissues were collected to measure the expression of LZTR1 by Real time PCR. Colon cancer SW620 cell lines were cultured and randomly divided into control group and LZTR1 group followed by analysis of LZTR1 expression by real time PCR, cell proliferation by MTT assay, Caspase3 activity, Bcl-2 and Bax level by Real time PCR, cell invasion by Transwell chamber; NF-κB/VEGF expression by Western blot. LZTR1 expression was significantly reduced in colon cancer tissues compared to adjacent tissues (P P κB and VEGF (P κB/VEGF signaling pathway.

Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first-line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second-line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first-line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1-14.5). Only four (20%) patients were observed of the grade 3 treatment-related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently.

Media coverage of the Winter Olympic Games provides an invaluable opportunity for athletes to promote themselves to a global audience that otherwise would not be reached through regular calendar events. An important element of athlete promotion occurs during press conferences when athletes speak to global media after winning a medal. The purpose of this study was to investigate how Olympic medalists presented themselves in front of the media aft er achieving Olympic success. A thematic analysis was conducted using press conference transcripts from 307 Olympic medalists during the 2018 PyeongChang Winter Olympic Games. The results indicated that athletes were likely to use media opportunities to self-promote their achievements, share secrets and stories, exhibit gratefulness, protest, show patriotism, and provide expert opinion. Overall, six categories of self-presentation were identified and discussed. Practical and theoretical implications are offered throughout, including a contribution to self-presentation theory and suggestions for athlete media literacy training.

Rapid detection and response to visual threats are critical for survival in animals. The amygdala (AMY) is hypothesized to be involved in this process, but how it interacts with the visual system to do this remains unclear. By recording flash-evoked potentials simultaneously from the superior colliculus (SC), lateral posterior nucleus of the thalamus, AMY, lateral geniculate nucleus (LGN) and visual cortex, which belong to the cortical and subcortical pathways for visual fear processing, we investigated the temporal relationship between these regions in visual processing in rats. A quick flash-evoked potential (FEP) component was identified in the AMY. This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC, which was assumed to be an important area in visual fear. This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection, but was diminished by RU38486, a glucocorticoid receptor blocker. By injecting a monosynaptic retrograde AAV tracer into the AMY, we found that it received a direct projection from the retina. These results confirm the existence of a direct connection from the retina to the AMY, that the latency in the AMY to flashes is equivalent to that in the sensory thalamus, and that the response is modulated by glucocorticoids.

We previously reported that cyclin D1 silencing interferes with RAD51 accumulation and increases the sensitivity of BRCA1 wild-type ovarian cancer cells to olaparib. However, the mechanisms associated with cyclin D1 overexpression in ovarian cancer are not fully understood. TargetScan predicted the potential binding sites for microRNA-20b (miR-20b) and the 3′-untranslated region of cyclin D1 mRNA; thus, we used luciferase reporter assay to verify those binding sites. The Kaplan-Meier method and log-rank test were used to examine the relationship between miR-20b and progression-free survival of ovarian cancer patients in The Cancer Genome Atlas ( n = 367) dataset. In vitro experiments were performed to evaluate the effects of miR-20b on cyclin D1 expression, cell cycle and response to olaparib. A peritoneal cavity metastasis model of ovarian cancer was established to determine the effect of miR-20b on the sensitivity of olaparib. Immunohistochemistry was performed to evaluate molecular mechanisms. In this work, we demonstrated that miR-20b down-regulates cyclin D1, increases the sensitivity of ovarian cancer cells to olaparib, reduces the expression of RAD51, and induces cell cycle arrest in G0/G1 phase. Ovarian cancer patients with higher expression of miR-20b had significantly longer progression-free survival. These results indicate that miR-20b may be a potential clinical indicator for the sensitivity of ovarian cancer to olaparib and the survival of ovarian cancer patients. Our findings suggest that miR-20b may have therapeutic value in combination with olaparib treatment for ovarian cancer.