Comprehensive pan-cancer analysis reveals CDC6 as a potential immunomodulatory agent and promising therapeutic target in pancreatic cancer.

Background: CDC6 is critical in DNA replication initiation, but its expression patterns and clinical implications in cancer are underexplored. This study uses multi-omics data from The Cancer Genome Atlas (TCGA) to comprehensively analyze CDC6 across various cancers, aiming to evaluate its potential as a prognostic biomarker and explore its role in immunotherapy. Methods: By leveraging multi-omics data from TCGA, we conducted a comprehensive analysis of CDC6 expression across a variety of cancer types. Least absolute shrinkage and selection operator (LASSO) regression was employed to assess the association of CDC6 with key molecules implicated in pancreatic cancer. Results: CDC6 expression was found to be significantly upregulated across a broad spectrum of cancers. High levels of CDC6 expression were associated with poor prognosis in several cancer types. Notable associations were observed between CDC6 expression and tumor mutational burden (TMB), microsatellite instability (MSI), as well as immune cell infiltration. Co-expression analysis revealed significant associations between CDC6 and prevalent immune checkpoint genes. A risk model incorporating CDC6-related genes, including CCNA1, CCNA2, CCND1, CCND2, CDC25B, CDC6, and CDK2, was developed for pancreatic cancer. Conclusions: CDC6 emerges as a promising prognostic biomarker and a potential target for immunotherapy across various cancers, including pancreatic cancer. It appears to modulate immune responses across cancer types, highlighting its regulatory role. Further exploration into the biological functions and clinical implications of CDC6 is warranted.

Prognosis and influencing factors of ER-positive, HER2-low breast cancer patients with residual disease after neoadjuvant chemotherapy: a retrospective study.

Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN_stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT_stage (P = 0.015), pN_stage (P = 0.029), ER (P = 0.020) and Ki67 (P < 0.001) levels after NACT were related to 5-year DFS in ER-positive, HER2-low patients with residual disease. Our study suggested that high proliferation, low ER expression and advanced stage before and after NACT are associated with a poor prognosis, providing useful information for developing long-term treatment strategies for ER-positive, HER2-low breast cancer in patients with residual disease in the future.

A new minimal invasive technique with in-situ stent-graft fenestration for type A aortic dissection.

Background: Aortic surgery successfully improves the prognosis of patients with type A aortic dissection. However, total arch replacement and reconstruction remain challenging. This study presents a new surgical modality, the in-situ stent-graft fenestration (ISSF) technique, for simplifying aortic arch reconstruction and assesses its short-term efficacy and safety in patients with type A aortic dissection. Methods: Data from 177 patients with type A aortic dissection who underwent aortic arch reconstruction were retrospectively analyzed. Sun's procedure was performed in 90 patients and ISSF was performed in the other 87. Results: The in-hospital mortality rate was 7.8% in the Sun's procedure group and 3.4% in the ISSF group (p = 0.357). Compared to the Sun's procedure group, the ISSF group had significantly shorter surgical duration, cardiopulmonary bypass time, circulatory arrest time, mechanical ventilation time, and aortic cross-clamp time (p < 0.05). Additionally, intraoperative blood loss was lower in the ISSF group than in the Sun's procedure group (p < 0.05). Patients who underwent ISSF also had a lower incidence of postoperative complications, including lung injury, renal failure, peripheral nerve injury, and chylothorax, than those who underwent Sun's procedure (p < 0.05). During the 6-month follow-up period after surgery, both groups showed significant improvements in the true lumen diameter of the descending thoracic aorta post-operation compared with the pre-operation measurements; meanwhile, the false lumen diameter decreased (p < 0.05). Conclusions: The ISSF technique appears to be an effective and safe alternative to conventional surgical procedures for patients with type A aortic dissection, with the potential to simplify the procedure, shorten the operation time, and yield satisfactory operative results. However, further investigation is needed to determine its long-term benefits.

S-NiSe/HG Nanocomposites with Balanced Dielectric Loss Encapsulated in Room-Temperature Self-Healing Polyurethane for Microwave Absorption and Corrosion Protection.

Exploring anticorrosion electromagnetic wave (EMW) absorbing materials in harsh conditions remains a challenge. Herein, S-NiSe/HG nanocomposites encapsulated in room-temperature self-healing polyurethane (S-NiSe/HG/SPU) were exploited as superior anticorrosion EMW absorbing materials. A dual-defect engineering collaborative Schottky interface construction endows S-NiSe/HG with a high vacancy concentration, abundant defects, and moderate conductivity. These structural merits synergistically balance dielectric loss by enhancing dipole-interface polarization loss and optimizing conduction loss. As a result, S-NiSe/HG demonstrates the optimal EMW absorption performance with a minimum reflection loss (RLmin) of -54.8 dB and an adequate absorption bandwidth (EAB) of 7.1 GHz. Besides, S-NiSe/HG/SPU combines the maze effect of S-NiSe/HG with the active repair capability of SPU, thereby providing long-term corrosion resistance for the Mg alloy. Even under corrosion for 10 days, S-NiSe/HG/SPU affords a low corrosion current density (1.3 × 10-5 A) and high charge transfer resistance (3796 Ω cm2). Overall, this work provides valuable insights for in-depth exploration of dielectric loss and development of multifunctional EMW-absorbing materials.

A liposomal etoposide with a sustained drug release effectively alleviated the therapy-related leukemia.

Etoposide (VP16) can induce therapy-related leukemia, which is reported to occur less frequently with a prolonged dose schedule. Therefore, we hypothesized that nanocarriers could decrease the VP16-induced leukemogenesis by reducing the rate of VP16 exposure via a sustained drug release. To test our hypothesis, the VP16-loaded liposome with a slow drug release behavior was constructed by encapsulating a rapidly-cleaved VP16-maleimide conjugate into liposomes using a glutathione-gradient loading method, and its toxicities and in vivo antitumor efficacy were compared with free VP16 in the LLC lung cancer xenograft. It was found that the repeated injection of free VP16 induced severe splenomegaly, lymphocytosis, and extensive lymphocyte infiltration in various tissues, indicating a sign of VP16 therapy-related leukemia. By contrast, the liposomal VP16 not only remarkably alleviated the syndrome of leukemogenesis, but also exhibited significantly enhanced antitumor activity as compared with free VP16 at the same dose. These results highlighted that the liposomal VP16 having a sustained drug release could effectively decrease the toxicity of leukemogenesis, which provided a new warranty to develop liposomal VP16 as a safe alternative to the commercial VP16 injection.

Structural basis of white-tailed deer, Odocoileus virginianus, ACE2 recognizing all the SARS-CoV-2 variants of concern with high affinity.

SARS-CoV-2 has been expanding its host range, among which the white-tailed deer (WTD), Odocoileus virginianus, became the first wildlife species infected on a large scale and might serve as a host reservoir for variants of concern (VOCs) in case no longer circulating in humans. In this study, we comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. We further determined the complex structures of WTD ACE2 with PT, Omicron BA.1, and BA.4/5 S trimer. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding. This study deepens our understanding of the interspecies transmission mechanisms of SARS-CoV-2 and further addresses the importance of constant monitoring on SARS-CoV-2 infections in wild animals. IMPORTANCE Even if we manage to eliminate the virus among humans, it will still circulate among wildlife and continuously be transmitted back to humans. A recent study indicated that WTD may serve as reservoir for nearly extinct SARS-CoV-2 strains. Therefore, it is critical to evaluate the binding abilities of SARS-CoV-2 variants to the WTD ACE2 receptor and elucidate the molecular mechanisms of binding of the RBDs to assess the risk of spillback events.

Simplified total arch reconstruction with a stented graft for extended aortic arch dilation.

Background: Reconstruction of the aortic arch and its three supra-aortic vessels remains a great surgical challenge with postoperative complications. We present a simplified total arch reconstruction with a modified stent graft (s-TAR) and compared its operative outcomes with conventional total arch replacement (c-TAR). Methods: This retrospective analysis of prospectively collected data from all consecutive patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and aortic arch reconstruction with the s-TAR or c-TAR between 2018 and 2021. The indication for intervention was maximum diameter of ascending aorta >55 mm and aortic arch in zone II >35 mm. Results: A total of 84 patients were analyzed: 43 in the s-TAR group and 41 in the c-TAR group. No inter-group differences were found for sex, age, comorbidities, or EuroSCORE II results. All patients were successfully treated with s-TAR or c-TAR, and none died intraoperatively. Cardiopulmonary bypass, selective cerebral perfusion, and lower-body circulatory arrest time were significantly shorter in the s-TAR group, which also had a lower incidence of prolonged ventilation and transient neurologic dysfunction. No patient in either group experienced permanent neurologic dysfunction. The incidence of recurrent laryngeal nerve injury and paraplegia was markedly increased in the c-TAR group; however, no such events were observed in the s-TAR group. Both perioperative blood loss and the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The in-hospital mortality rate was 0% in the s-TAR group and 4.9% in the c-TAR group. The s-TAR group had significantly shorter intensive care unit (ICU) stay and lower total hospitalization costs. Conclusions: The s-TAR technique is a safe and effective alternative for total arch reconstruction with shorter operation time, lower rate of postoperative complications and lower total hospitalization costs compared with c-TAR.

Biodegradable Microneedles Array with Dual-Release Behavior and Parameter Optimization by Finite Element Analysis.

Microneedles (MNs) are particularly attractive for transdermal administration because of the improved safety, patient compliance and convenience. Dissolving MNs could provide rapid transdermal delivery, but with relatively low mechanical strength and almost no sustainability. On the other hand, hydrogel MNs are complicated to fabricate and have risk concerns. Herein, we developed a biodegradable MNs array composed of biocompatible silk fibroin and poly(vinyl alcohol) to overcome these limitations. Finite element analysis was employed for parameter optimization. The MNs array fabricated by the optimal parameters and material displayed sufficient mechanical strength to disrupt stratum corneum and formed microchannels for transdermal delivery. Dual-release profile was observed in the MNs array, with rapid release in the beginning, and prolonged release afterward. This release behavior fits Weibull release model and is favorable for topical application. The initial immediate release can quickly deliver active compounds to reach the therapeutic effective concentration and facilitate skin penetration, and the sustained release may supply the skin with active compounds over a prolonged period. This biodegradable MNs array is easy to fabricate, mechanically robust, could eliminate safety concerns, and provide the sustainability and advantage for large-scale production.

Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

Cell Division Cycle-Associated Protein 3 (CDCA3) Is a Potential Biomarker for Clinical Prognosis and Immunotherapy in Pan-Cancer.

CDCA3 is an essential regulator in cell mitosis and can regulate many physiological and pathological processes in the human body by stimulating certain proteins such as cell cycle regulatory proteins, transcription factors, and signal transduction molecules. Although several studies have shown that dysregulation of CDCA3 is a common phenomenon in human cancers, no systematic pan-cancer analysis has been performed. In this study, we comprehensively investigated the role of CDCA3 in 33 human cancer types by utilizing multiple cancer-related databases and bioinformatics analysis tools, including TCGA, GTEx, GEPIA, TIMER, STRING, Metascape, and Cytoscape. Evidence from bioinformatics databases shows that CDCA3 is overexpressed in almost all human cancer types, and its overexpression is significantly associated with survival in patients with more than ten cancer types. CDCA3 expression positively correlates with immune cell infiltration levels in multiple human cancer types. Furthermore, the results of the GSEA analysis revealed that overexpression of CDCA3 may promote the malignant progression of cancer by activating various oncogenic signaling pathways in human cancers. In conclusion, our pan-cancer analysis provides a comprehensive overview of the oncogenic role of CDCA3 in multiple human cancer types, suggesting that CDCA3 may serve as a potential therapeutic target and prognostic biomarker in multiple human cancer types.

Clinical significance of multi-genic assay in identifying aggressive papillary thyroid carcinoma.

BACKGROUND: A minority of papillary thyroid carcinoma (PTC) is highly aggressive, with rapid progression and a poor prognosis. This study investigated the ability of multi-genic assay to identify patients with aggressive PTC. PATIENTS AND METHODS: A total of 117 PTC patients treated at The First Affiliated Hospital of Chongqing Medical University with clinicopathological data and multi-genic assay results and 389 patients with complete data from The Cancer Genome Atlas (TCGA) database were included. The chi-square test was used to analyze the relationship between the multi-genic assay results and clinicopathological characteristics. Univariate and multivariate regression analyses were used to analyze the impact of various factors on prognosis. RESULTS: The median follow-up times of the local and TCGA cohorts were 30 months and 34 months, respectively. The results showed that central lymph node metastasis (P = 0.036), lateral lymph node metastasis (P = 0.003) and mutations in genes other than BRAFV600E (P = 0.002) were significantly associated with disease-free survival (DFS) in the local cohort, while the analysis of TCGA data showed that mutations in genes other than BRAFV600E were significantly related to poor prognosis (P = 0.029). According to univariate and multivariate analyses, mutations in genes other than BRAFV600E (P = 0.021) and lateral lymph node metastasis (P = 0.022) were independent factors for postoperative recurrence, as well as, mutations in genes other than BRAFV600E were an independent factor of survival (P = 0.047). CONCLUSIONS: The multi-genic assay was able to identify aggressive PTC, providing an effective biological basis for surgical management and postoperative treatment.

Structural basis of SARS-CoV-2 and its variants binding to intermediate horseshoe bat ACE2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. Intermediate horseshoe bats (Rhinolophus affinis) are hosts of RaTG13, the second most phylogenetically related viruses to SARS-CoV-2. We report the binding between intermediate horseshoe bat ACE2 (bACE2-Ra) and SARS-CoV-2 receptor-binding domain (RBD), supporting the pseudotyped SARS-CoV-2 viral infection. A 3.3 Å resolution crystal structure of the bACE2-Ra/SARS-CoV-2 RBD complex was determined. The interaction networks of Patch 1 showed differences in R34 and E35 of bACE2-Ra compared to hACE2 and big-eared horseshoe bat ACE2 (bACE2-Rm). The E35K substitution, existing in other species, significantly enhanced the binding affinity owing to its electrostatic attraction with E484 of SARS-CoV-2 RBD. Furthermore, bACE2-Ra showed extensive support for the SARS-CoV-2 variants. These results broaden our knowledge of the ACE2/RBD interaction mechanism and emphasize the importance of continued surveillance of intermediate horseshoe bats to prevent spillover risk.

Remote drug loading into liposomes via click reaction.

The development of liposome-based drugs was severely limited due to inefficient loading strategies. Herein, we developed a click reaction-mediated loading procedure by designing an enzyme-sensitive maleimide (MAL) tag for ferrying chemotherapeutics into preformed liposomes containing glutathione (GSH). Based on this strategy, various hydrophobic drugs could be encapsulated into liposomes within 5-30 min with encapsulation efficiency >95% and loading capacity of 10-30% (w/w). The entrapped cargo could be slowly released from the liposomes, followed by rapid enzyme-mediated conversion into active drugs to exert antitumor activity under physiological conditions. The resulting drug-loaded liposomes significantly prolonged the blood circulation of cargos and displayed more potent in vivo antitumor efficacy than free drugs at the equitoxic dose. More importantly, this method is a remote drug loading strategy in nature, which is suitable for industrial production. This is the first demonstration of active loading of MAL-tagged chemotherapeutics in liposomes for improved antitumor efficacies, which has the potential to serve as a universal drug loading strategy for the development of liposomal formulations of chemotherapeutics.

Long noncoding RNA KB-1980E6.3 promotes breast cancer progression through the PI3K/AKT signalling pathway.

This research aims to investigate the effect of lncRNA KB-1980E6.3 on the biological behaviour of breast cancer cells under normoxic conditions and the underlying molecular mechanism. The expression of KB-1980E6.3 in breast cancer tissues and cells was detected by RT-qPCR. The proliferation, migration and invasion of cells were evaluated by CCK-8, colony formation, scratch and Transwell assays; KB-1980E6.3-related xenograft models were established for in vivo studies. The protein expression of PI3K, p-PI3K, AKT and p-AKT was validated by western blotting analysis. The levels of KB-1980E6.3 are significantly upregulated in breast cancer tissues and cells and are related to the poor prognosis. Functional research both in vivo and in vitro revealed that the downregulation of KB-1980E6.3 expression significantly decreased cell proliferation, invasion and migration, while ectopic KB-1980E6.3 expression obviously promoted these biological phenotypes. In terms of the mechanism, KB-1980E6.3 is involved in the activation of the PI3K/AKT signalling pathway. Knockdown of KB-1980E6.3 reduced the expression of the p-PI3K and p-AKT proteins, whereas KB-1980E6.3 overexpression showed the opposite result. The agonist 740Y-P and inhibitor LY294002 reversed the effect of KB-1980E6.3 knockdown and overexpression on the PI3K/AKT pathway in BC cells. KB-1980E6.3 promotes the proliferation, invasion and migration of breast cancer cells by activating PI3K/AKT signalling, which can be used as a potential target for breast cancer therapy.

Exploring the influencing factors of the pathologic complete response in estrogen receptor-positive, HER2-negative breast cancer after neoadjuvant chemotherapy: a retrospective study.

BACKGROUND: Pathological complete response (pCR) is the goal of neoadjuvant chemotherapy (NACT). We aimed to develop a nomogram to predict the probability of achieving pCR in estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer patients. METHODS: A total of 273 ER+, HER2- breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to screen the predictive factors to develop the nomograms. The discrimination and calibration abilities were assessed by the C-index, receiver operating characteristic curve (AUC), and calibration plot. RESULTS: There were 28 patients (10.3%) with overall pCR, 38 patients (13.9%) with breast pCR after NACT. ER expression, PgR expression, the neutrophil-to-lymphocyte ratio (NLR) and the Ki-67 index were independent predictive factors for achieving overall pCR. These indicators had good discrimination and calibration ability (AUC 0.843). The nomogram for breast pCR was established based on ER expression, PgR expression, the NLR, and the Ki-67 index and showed great discriminatory ability, with an AUC of 0.810. The calibration curve showed that the predictive ability of the nomogram was a good fit to actual observations. CONCLUSION: The nomograms exhibited a sufficient discriminatory ability for predicting pCR after NACT in ER+, HER2- breast cancer patients. Utilizing these nomograms will enable us to identify patients at high probability for pCR after NACT and provide a reference for preoperative adjuvant therapy.

Efficacy evaluation of neoadjuvant chemotherapy in patients with HER2-low expression breast cancer: A real-world retrospective study.

Background: To characterize the clinicopathological features and evaluate the neoadjuvant chemotherapy (NACT) efficacy of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer. Methods: A total of 905 breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled, including 685 cases with HER2-low expression and 220 cases with HER2-negative expression. Clinicopathological features were compared between patients with HER2-negative and HER2-low expression. Univariate and multivariate logistic regression analyses were used to find the independent factors of achieving a pathological complete response (pCR) after NACT. Results: There were significant differences in stage_N (P = 0.014), histological grade (P = 0.001), estrogen receptor (ER) status (P < 0.001), progesterone receptor (PgR) status (P < 0.001), NACT regimens (P = 0.032) and NACT efficacy (P = 0.037) between patients with HER2-negative and HER2-low expression breast cancer. In subgroup analysis, histological grade (P = 0.032), ER (P = 0.002), Ki-67 (P < 0.001) and HER2 status (P = 0.025) were independent predictors of achieving a pCR in ER-positive breast cancer. And the nomogram for pCR in ER-positive breast cancer showed great discriminatory ability with an AUC of 0.795. The calibration curve also showed that the predictive ability of the nomogram was a good fit to actual observations. Then, in the analysis of ER-negative breast cancer, only stage_N (P = 0.001) and Ki-67 (P = 0.018) were independent influencing factors of achieving a pCR in ER-negative breast cancer. Conclusion: HER2-low breast cancer was a different disease from HER2-negative breast cancer in clinicopathological features. Moreover, the NACT efficacy of HER2-low breast cancer patients was poorer.

Prediction Model of Pathologic Central Lymph Node Negativity in cN0 Papillary Thyroid Carcinoma.

BACKGROUND: Most patients with papillary thyroid carcinoma (PTC) have an excellent prognosis. Although central lymph node invasion is frequent, management via central lymph node dissection (CLND) remains controversial. The present study retrospectively investigated independent predictors of pathologic central lymph node negativity (pCLN-) and established a prediction model for pCLN- in clinical lymph node negativity (cN0) PTC. METHODS: A total of 2,687 patients underwent thyroid surgery for cN0 PTC from 2013 to 2018 at the First Affiliated Hospital of Chongqing Medical University, and lobectomy plus ipsilateral CLND was the basic surgical extent. Clinicopathological characteristics were reviewed and analyzed. Univariate and multivariate analyses were performed to identify factors related to pCLN-. A prediction model was established based on the results of multivariate analyses. RESULTS: The pCLN- rate was 51.5% (1,383/2,687). Multivariate analysis revealed that sex, age, thyroid stimulating hormone (TSH), size, location, laterality, unifocality and extrathyroidal extension negativity (ETE-) were independent predictors of pCLN-. The nomogram showed good discriminative ability (C-index: 0.784 and 0.787 in derivation and validation groups, respectively) and was well calibrated. We quantified the clinical usefulness of the nomogram by decision curve analysis. The median length of follow-up was 30 (range 12- 83) months, and 190 cases were lost, with a follow-up rate of 92.9% (2,497/2,687). Of the 2,687 patients included, 21 (0.8%) experienced recurrence. CONCLUSION: This nomogram, which integrates available preoperative clinicopathological features and intraoperative frozen biopsy outcomes, is a reliable tool with high accuracy to predict pCLN- in cN0 PTC.

A pseudo-targeted metabolomics study based on serum bile acids profiling for the differential diagnosis of benign and malignant breast lesions.

INTRODUCTION: Breast cancer (BC) has become the most commonly diagnosed cancer worldwide. It is very critical for the differential diagnosis between BC and benign breast diseases (BBD). The characteristics of serum bile acids (BAs) profiling in patients with BBD and BC was elucidated so that potential biomarkers could be find out for the differential diagnosis of BC and BBD. METHODS: A pseudo-targeted approach was used to perform BAs metabolomics analysis in serum of 29 patients with BBD and 47 patients with BC by ultra-high performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Partial least squares-discriminant analysis (PLS-DA) was used to establish a differential diagnostic model for BC, and the receiver operating characteristic (ROC) curve and logistic regression analysis were used to screen out bile acids as biomarkers for the differential diagnosis of BC and BBD. RESULTS: The serum BAs profile in BC group was quite different from that in BBD group. Compared with the BBD group, BC group had higher level of chenodeoxycholic acid (CDCA), while they had lower levels of dihydroxy tauro-conjugated BA (Tdi-1) and sulfated dihydroxy glyco-conjugated BA (Gdi-S-1). The sensitivity and specificity of PLS-DA model for patients classification were 100% and 92.3%, respectively. The combined biomarker, CDCA and Tdi-1, had high efficacy for the differential diagnosis (area under the curve was 0.954, 95% CI: 0.880-1.000) of BC. Besides, the performance was superior to traditional biomarkers in the differential diagnosis of BC with or without comorbidities. CONCLUSION: The profile of serum BAs in women with BC was quite different from that in patients with BBD. Serum BAs profiling analysis could be used as an effective tool for the differential diagnosis of BC and BBD.

Identification of candidate RNA signatures in triple-negative breast cancer by the construction of a competing endogenous RNA network with integrative analyses of Gene Expression Omnibus and The Cancer Genome Atlas data.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characterized by aggressive and metastatic clinical characteristics and generally leads to earlier distant recurrence and poorer prognosis than other molecular subtypes. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) serve a crucial role in a wide variety of biological processes by interacting with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) and, thus, affect the expression of target genes in multiple types of cancer. Seven datasets from the Gene Expression Omnibus (GEO) database, including 444 tumor and 88 healthy tissue samples, were utilized to investigate the underlying mechanisms of TNBC and identify prognostic biomarkers. Differentially expressed genes (DEGs) were further validated in The Cancer Genome Atlas database and the associations between their expression levels and clinical information were analyzed to identify prognostic values. A potential lncRNA-miRNA-mRNA ceRNA network was also constructed. Finally, 69 mRNAs from the integrated Gene Expression Omnibus datasets were identified as DEGs using the robust rank aggregation method with |log2FC|>1 and adjusted P<0.01 set as the significance cut-off levels. In addition, 29 lncRNAs, 21 miRNAs and 27 mRNAs were included in the construction of the ceRNA network. The present study elucidated the mechanisms underlying the progression of TNBC and identified novel prognostic biomarkers for TNBC.

Extracorporeal membrane oxygenation (ECMO) assisted mediastinal tumor resection and superior vena cava replacement are safe and feasible.

BACKGROUND: How to maximally improve the drainage of intracranial and upper body venous and to reduce neurological complications during thoracic tumor-causedsuperior vena cava replacement are still clinical problems to be solved. METHODS: We have innovatively used the bilateral jugular vein-left femoral vein ECMO shunting to perform mediastinal tumor resection and superior vena cava replacement in a 50-year-old woman. RESULTS: During the operation, this technique maintained the patient's hemodynamic stability, improved the cerebral oxygen saturation and reduced the cerebral ischemia, hypoxia as well as the neurological complications. CONCLUSION: It is indicated for patients with superior vena cava replacement who are unable to perform venous bypass (such as innominate vein to right atrial bypass) or venous shunting (such as differential pressure drainage from internal jugular vein to femoral vein).