Effect of Tranexamic Acid on Hidden Blood Loss in Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion: A Retrospective Study.

Purpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss. Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events. Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group. Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.

Unveiling hotspots and trends in hip arthroscopy research: A bibliometric and visualized analysis (1900-2022).

Over the past 10 years, hip arthroscopy has been increasingly employed to effectively diagnose and safely treat a range of hip pathologies. With research related to hip arthroscopy continually expanding, the number of articles connected with hip arthroscopy has also consistently grown. We aimed to investigate trends and hotspots in hip arthroscopy-related research, and analyze the top 100 most-cited articles on hip arthroscopy. We searched for ("hip arthroscopy") AND ("article" OR "review") AND "English" in the Web of Science database from 1900 to 2022, which was used to obtain all publications relating to hip arthroscopy. Distribution of country, affiliated institution, journal, authors, citation frequency and keywords were analyzed using VOSviewer. A total of 1094 articles were selected from the Web of Science Core Collection (WoSCC) from 1900 to 2022. The number of publications concerning hip arthroscopy displayed an ascending trend over time. Among the countries, the United States emerged as the largest contributor to the number of articles. The highest prolific institution was American Hip Institute. Among the journals, the highest-ranking journal was "Arthroscopy-the Journal of Arthroscopic and Related Surgery," with 8316 citation counts and 262 articles. The area of greatest research interest was diagnosis and therapy in the field. The scientific articles on the subject of hip arthroscopy have risen continuously in recent years. The United States was the most influential country and made the most significant contributions to this field globally. We identified the research direction and trend for the first time and provided the most recent bibliometric analysis on hip arthroscopy, which may assist researchers in conducting studies on hip arthroscopy.

Current understanding of subjective tinnitus in adults.

PURPOSE: An up-to-date overview of epidemiology, etiology and pathophysiological mechanisms, diagnostic and evaluation methods, current treatment status and future directions of subjective tinnitus in adults. METHODS: Review of current evidence-based literature on subjective tinnitus in adults. RESULTS: The prevalence of subjective tinnitus in the adult population is estimated to be around 14%, and it tends to increase with age. Subjective tinnitus is a complex condition with multiple factors contributing to its origin. However, the exact causes and underlying mechanisms remain unknown. Potential causes may include hearing loss, dysfunction in the somatosensory system, and auditory cortical dysfunction, although severe underlying pathology is rare. Currently, diagnosis primarily relies on patient self-reported medical history and physician-based clinical assessment due to the lack of objective testing. Various treatment and management options have been proposed, but their effectiveness varies, and there is no universally agreed-upon treatment option. CONCLUSIONS: Tinnitus is a complex and heterogeneous disease with a high incidence rate and a tendency to increase with age. A holistic perspective is needed to understand the generation, perception, and emotional responses to tinnitus. Diagnosis requires a comprehensive assessment based on medical history and relevant examinations, identification of concurrent psychosomatic comorbidities, and active pursuit of objective diagnostic methods. At the same time, on the basis of existing treatment plans and combining emerging technologies, we will develop new personalized, precise, and combined treatment plans.

Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets.

Cancer cells frequently change their metabolism from aerobic glycolysis to lipid metabolism and amino acid metabolism to adapt to the malignant biological behaviours of infinite proliferation and distant metastasis. The significance of metabolic substances and patterns in tumour cell metastasis is becoming increasingly prominent. Tumour metastasis involves a series of significant steps such as the shedding of cancer cells from a primary tumour, resistance to apoptosis, and colonisation of metastatic sites. However, the role of glutamine in these processes remains unclear. This review summarises the key enzymes and transporters involved in glutamine metabolism that are related to the pathogenesis of malignant tumour metastasis. We also list the roles of glutamine in resisting oxidative stress and promoting immune escape. Finally, the significance of targeting glutamine metabolism in inhibiting tumour metastasis was proposed, research in this field improving our understanding of amino acid metabolism rewiring and simultaneously bringing about new and exciting therapeutic prospects.

LINC00482 sponged miR-2467-3p to promote bone metastasis of prostate cancer through activating Wnt/ß-catenin signaling pathway.

This study was designed to investigate the biological functions of LINC00482 in prostate cancer (PCa) with bone metastasis. TCGA dataset of PCa was applied for LINC00482 expression analysis and real time PCR was used to verify the expression level of LINC00482 in PCa tissues as well as PCa bone metastatic tissues. To detect the biological functions of LINC00482 in vitro, various assays were used including CCK-8, EdU, colony formation and transwell assays. The biological functions of LINC00482 were also identified in vivo by inoculating PCa cells into the left cardiac ventricle of mice, followed by evaluating the osteolytic lesions and osteolytic score. In addition, Starbase and Lncbase databases were applied for predicting the potential target miRNA of LINC00482, while TargetScan and Starbase databases were used for predicting the potential target of miRNA. The luciferase reporter assay was utilized to determine the interactions among these molecules and western blotting was employed to verified the targeted proteins. Results showed that high expression level of LINC00482 was observed in bone metastatic PCa tissues and associated with PCa progression. Silencing of LINC00482 inhibited cell proliferation, migration and invasion in PCa. Furthermore, LINC00482 was proved to act as a competing endogenous RNA by sponging miR-2467-3p to activate Wnt/ß-catenin signaling pathway, which may be a promising therapeutic target for PCa with bone metastasis.

A Case Report of a Bilateral Carotid Body Tumor and a Review of Its Imaging Manifestations.

Bilateral carotid body tumors (CBTs) are extremely uncommon. In recent years, some clinical cases have been documented. A case of bilateral CBT is reported with a review of its imaging manifestations. When a unilateral CBT is discovered, assessment of the contralateral site is essential. The 'goblet' sign is a characteristic imaging feature of CBT. The preferred imaging modality is computed tomography angiography. Teaching Point: When a carotid body tumor is suspected on one side, careful examinationof the contralateral side is essential; The preferred imaging approach is CTA.

Bone metastasis risk and prognosis assessment models for kidney cancer based on machine learning.

Background: Bone metastasis is a common adverse event in kidney cancer, often resulting in poor survival. However, tools for predicting KCBM and assessing survival after KCBM have not performed well. Methods: The study uses machine learning to build models for assessing kidney cancer bone metastasis risk, prognosis, and performance evaluation. We selected 71,414 kidney cancer patients from SEER database between 2010 and 2016. Additionally, 963 patients with kidney cancer from an independent medical center were chosen to validate the performance. In the next step, eight different machine learning methods were applied to develop KCBM diagnosis and prognosis models while the risk factors were identified from univariate and multivariate logistic regression and the prognosis factors were analyzed through Kaplan-Meier survival curve and Cox proportional hazards regression. The performance of the models was compared with current models, including the logistic regression model and the AJCC TNM staging model, applying receiver operating characteristics, decision curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts. Results: Our prognosis model achieved an AUC of 0.8269 (95%CI: 0.8083-0.8425) in the internal validation cohort and 0.9123 (95%CI: 0.8979-0.9261) in the external validation cohort. In addition, we tested the performance of the extreme gradient boosting model through decision curve analysis curve, Precision-Recall curve, and Brier score and two models exhibited excellent performance. Conclusion: Our developed models can accurately predict the risk and prognosis of KCBM and contribute to helping improve decision-making.

A visualized dynamic prediction model for survival of patients with geriatric thyroid cancer: A population-based study.

Objective: Thyroid cancer (TC) is a common malignancy with a poor prognosis with aging. However, no accurate predictive survival model exists for patients with geriatric TC.We aimed to establish prediction models of prognosis in elderly TC. Methods: We retrospectively reviewed the clinicopathology characteristics of patients with geriatric TC in the Surveillance, Epidemiology, and End Results database (SEER) from 2004 to 2018. The risk predictors used to build the nomograms were derived from the Cox proportional risk regression. These nomograms were used to predict 1-, 3-, and 5-year overall survival and cancer-specific survival in elderly patients with TC. The accuracy and discriminability of the new model were evaluated by the consistency index (C-index) and calibration curve. The clinical applicability value of the model was assessed using the decision curve analysis. Results: We used the SEER database to include 16475 patients with geriatric TC diagnosed from 2004 to 2018. The patients from 2004 to 2015 were randomly sorted out on a scale of 7:3. They were classified into a training group (n = 8623) and a validation group (n = 3669). Patients with TC diagnosed in 2016-2018 were classified into external validation groups (n = 4183). The overall survival nomogram consisted of 10 variables (age, gender, marital status, histologic type, grade, TNM stage, surgery status, and tumor size). A cancer-specific survival nomogram consisted of eight factors (age, tumor size, grade, histologic type, surgery, and TNM stage). The C-index values for the training, validation, and external validation groups were 0.775 (95% confidence interval [CI] 0.785-0.765), 0.776 (95% CI 0.792-0.760), and 0.895(95% CI 0.873-0.917), respectively. The overall survival was consistent with a nomogram based on the calibration curve. Besides, the decision curve analysis showed excellent clinical application value of the nomogram. Additionally, we found that surgery could improve the prognosis of patients with geriatric at high-risk (P < 0.001) but not those at low-risk (P = 0.069). Conclusion: This was the first study to construct predictive survival nomograms for patients with geriatric TC. The well-established nomograms and the actual results could guide follow-up management strategies.

Osteoporosis, fracture and survival: Application of machine learning in breast cancer prediction models.

The risk of osteoporosis in breast cancer patients is higher than that in healthy populations. The fracture and death rates increase after patients are diagnosed with osteoporosis. We aimed to develop machine learning-based models to predict the risk of osteoporosis as well as the relative fracture occurrence and prognosis. We selected 749 breast cancer patients from two independent Chinese centers and applied six different methods of machine learning to develop osteoporosis, fracture and survival risk assessment models. The performance of the models was compared with that of current models, such as FRAX, OSTA and TNM, by applying ROC, DCA curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts. Three models were developed. The XGB model demonstrated the best discriminatory performance among the models. Internal and external validation revealed that the AUCs of the osteoporosis model were 0.86 and 0.87, compared with the FRAX model (0.84 and 0.72)/OSTA model (0.77 and 0.66), respectively. The fracture model had high AUCs in the internal and external cohorts of 0.93 and 0.92, which were higher than those of the FRAX model (0.89 and 0.86). The survival model was also assessed and showed high reliability via internal and external validation (AUC of 0.96 and 0.95), which was better than that of the TNM model (AUCs of 0.87 and 0.87). Our models offer a solid approach to help improve decision making.

Two Novel Nomograms Predicting the Risk and Prognosis of Pancreatic Cancer Patients With Lung Metastases: A Population-Based Study.

Background: Pancreatic cancer (PC) is one of the most common malignant types of cancer, with the lung being the frequent distant metastatic site. Currently, no population-based studies have been done on the risk and prognosis of pancreatic cancer with lung metastases (PCLM). As a result, we intend to create two novel nomograms to predict the risk and prognosis of PCLM. Methods: PC patients were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database from 2010 to 2016. A multivariable logistic regression analysis was used to identify risk factors for PCLM at the time of diagnosis. The multivariate Cox regression analysis was carried out to assess PCLM patient's prognostic factors for overall survival (OS). Following that, we used area under curve (AUC), time-dependent receiver operating characteristics (ROC) curves, calibration plots, consistency index (C-index), time-dependent C-index, and decision curve analysis (DCA) to evaluate the effectiveness and accuracy of the two nomograms. Finally, we compared differences in survival outcomes using Kaplan-Meier curves. Results: A total of 803 (4.22%) out of 19,067 pathologically diagnosed PC patients with complete baseline information screened from SEER database had pulmonary metastasis at diagnosis. A multivariable logistic regression analysis revealed that age, histological subtype, primary site, N staging, surgery, radiotherapy, tumor size, bone metastasis, brain metastasis, and liver metastasis were risk factors for the occurrence of PCLM. According to multivariate Cox regression analysis, age, grade, tumor size, histological subtype, surgery, chemotherapy, liver metastasis, and bone metastasis were independent prognostic factors for PCLM patients' OS. Nomograms were constructed based on these factors to predict 6-, 12-, and 18-months OS of patients with PCLM. AUC, C-index, calibration curves, and DCA revealed that the two novel nomograms had good predictive power. Conclusion: We developed two reliable predictive models for clinical practice to assist clinicians in developing individualized treatment plans for patients.

Application Progress of Gd-EOB-DTPA-Enhanced MRI T1 Mapping in Hepatic Diffuse Diseases.

BACKGROUND: In recent years, T1 mapping imaging based on Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has resulted in new research and clinical applications in hepatic diseases. OBJECTIVE: The objective of the study is to analyze, prospect, and summarize the Gd-EOB-DTPA- enhanced MRI T1 mapping technology in hepatic diseases in recent years. MAIN FINDINGS: Gd-EOB-DTPA-enhanced T1 mapping has been used more frequently in liver diseases regardless of 1.5T or 3.0T MRI equipment. Volume interpolated body examination (VIBE) mapping sequence seems to be the recommended MRI scan sequence. In the evaluation of T1 value on liver function, the hepatobiliary phase 10 minutes after enhancement is the recommended time point. The fat fraction and hepatic steatosis grade based on MRI-derived biomarkers are easier to implement and popularize than a liver biopsy. Gd-EOB-DTPA-enhanced MRI T1 mapping can not only be used to evaluate the degree of liver injury, the stage of liver fibrosis, and the liver reserve function of patients with liver cirrhosis but also to distinguish focal liver lesions and predict the differentiation degree of hepatocellular carcinoma. At the same time, it has some value in predicting tumor immunohistochemical indexes, such as Ki67, CD34. CONCLUSION: Gd-EOB-DTPA-enhanced MRI T1 mapping has great potential in the application of diffuse and focal liver lesions. It is a quantitative study, trying to select homogeneous research objects and try to use the same standards in scanning sequence and scanning time, especially for the study of liver function, which is a focus of future research. The research on the relationship between T1 value and tumor immunohistochemical indexes is worth consideration.

Identification and Validation of the Prognostic Stemness Biomarkers in Bladder Cancer Bone Metastasis.

BACKGROUND: Bladder urothelial carcinoma (BLCA) is one of the most common urinary system malignancies with a high metastasis rate. Cancer stem cells (CSCs) play an important role in the occurrence and progression of BLCA, however, its roles in bone metastasis and the prognostic stemness biomarkers have not been identified in BLCA. METHOD: In order to identify the roles of CSC in the tumorigenesis, bone metastasis and prognosis of BLCA, the RNA sequencing data of patients with BLCA were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) and the differential expressed genes (DEGs) were evaluated and identified. The associations between mRNAsi and the tumorigenesis, bone metastasis, clinical stage and overall survival (OS) were also established. The key prognostic stemness-related genes (PSRGs) were screened by Lasso regression, and based on them, the predict model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve and the risk score. Additionally, in order to explore the key regulatory network, the relationship among differentially expressing TFs, PSRGs, and absolute quantification of 50 hallmarks of cancer were also identified by Pearson correlation analysis. To verify the identified key TFs and PSRGs, their expression levels were identified by our clinical samples via immunohistochemistry (IHC). RESULTS: A total of 8,647 DEGs were identified between 411 primary BLCAs and 19 normal solid tissue samples. According to the clinical stage, mRNAsi and bone metastasis of BLCA, 2,383 stage-related DEGs, 3,680 stemness-related DEGs and 716 bone metastasis-associated DEGs were uncovered, respectively. Additionally, compared with normal tissue, mRNAsi was significantly upregulated in the primary BLCA and also associated with the prognosis (P = 0.016), bone metastasis (P < 0.001) and AJCC clinical stage (P < 0.001) of BLCA patients. A total of 20 PSRGs were further screened by Lasso regression, and based on them, we constructed the predict model with a relatively high accuracy (AUC: 0.699). Moreover, we found two key TFs (EPO, ARID3A), four key PRSGs (CACNA1E, LINC01356, CGA and SSX3) and five key hallmarks of cancer gene sets (DNA repair, myc targets, E2F targets, mTORC1 signaling and unfolded protein response) in the regulatory network. The tissue microarray of BLCA and BLCA bone metastasis also revealed high expression of the key TFs (EPO, ARID3A) and PRSGs (SSX3) in BLCA. CONCLUSION: Our study identifies mRNAsi as a reliable index in predicting the tumorigenesis, bone metastasis and prognosis of patients with BLCA and provides a well-applied model for predicting the OS for patients with BLCA based on 20 PSRGs. Besides, we also identified the regulatory network between key PSRGs and cancer gene sets in mediating the BLCA bone metastasis.

Antimicrobial peptide temporin-1CEa isolated from frog skin secretions inhibits the proinflammatory response in lipopolysaccharide-stimulated RAW264.7 murine macrophages through the MyD88-dependent signaling pathway.

Temporin-1CEa, which is isolated from the skin secretions of the Chinese brown frog Rana chensinensis, exhibits broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and antitumor activity. LK2(6) and LK2(6)A(L) are the analogs of temporin-1CEa obtained by replacing amino acids and displayed an improved anticancer activity. In the present study, the anti-inflammatory activity and mechanism of action of temporin-1CEa and its analogs LK2(6) and LK2(6)A(L) in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were investigated. The results showed that temporin-1CEa and its analogs decreased the production of the cytokines tumor necrosis factor-α and interleukin-6 by inhibiting the protein expression of nuclear factor-κB and mitogen-activated protein kinase and the MyD88-dependent signaling pathway. Isothermal titration calorimetry studies revealed that temporin-1CEa, LK2(6) and LK2(6)A(L) exhibited binding affinities to LPS, an important inflammatory inducer, with Kd values of 0.1, 0.03 and 0.06 µM, respectively. Circular dichroism and zeta potential experiments showed that temporin-1CEa and its analogs interacted with LPS by electrostatic binding between the positively charged peptides and negatively charged LPS, resulting in the neutralization of LPS toxicity.

Nomogram Predicts Risk and Prognostic Factors for Bone Metastasis of Pancreatic Cancer: A Population-Based Analysis.

Background: The overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low, and it is pretty hard to treat bone metastasis. However, there are currently no effective nomograms to predict the diagnosis and prognosis of pancreatic cancer with bone metastasis (PCBM). Therefore, it is of great significance to establish effective predictive models to guide clinical practice. Methods: We screened patients from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2016. The independent risk factors of PCBM were identified from univariable and multivariable logistic regression analyses, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors affecting the prognosis of PCBM. In addition, two nomograms were constructed to predict the risk and prognosis of PCBM. We used the area under the curve (AUC), C-index and calibration curve to determine the predictive accuracy and discriminability of nomograms. The decision curve analysis (DCA) and Kaplan-Meier(K-M) survival curves were employed to further confirm the clinical effectiveness of the nomogram. Results: Multivariable logistic regression analyses revealed that risk factors of PCBM included age, primary site, histological subtype, N stage, radiotherapy, surgery, brain metastasis, lung metastasis, and liver metastasis. Using Cox regression analyses, we found that independent prognostic factors of PCBM were age, race, grade, histological subtype, surgery, chemotherapy, and lung metastasis. We utilized nomograms to visually express data analysis results. The C-index of training cohort was 0.795 (95%CI: 0.758-0.832), whereas that of internal validation cohort was 0.800 (95%CI: 0.739-0.862), and the external validation cohort was 0.787 (95%CI: 0.746-0.828). Based on AUC of receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA), we concluded that the risk and prognosis model of PCBM exhibits excellent performance. Conclusion: Nomogram is sufficiently accurate to predict the risk and prognostic factors of PCBM, allowing for individualized clinical decisions for future clinical work.

Unimolecular Photodynamic O2-Economizer To Overcome Hypoxia Resistance in Phototherapeutics.

Tumor hypoxia has proven to be the major bottleneck of photodynamic therapy (PDT) to clinical transformation. Different from traditional O2 delivery approaches, here we describe an innovative binary photodynamic O2-economizer (PDOE) tactic to reverse hypoxia-driven resistance by designing a superoxide radical (O2•-) generator targeting mitochondria respiration, termed SORgenTAM. This PDOE system is able to block intracellular O2 consumption and down-regulate HIF-1α expression, which successfully rescues cancer cells from becoming hypoxic and relieves the intrinsic hypoxia burden of tumors in vivo, thereby sparing sufficient endogenous O2 for the PDT process. Photosensitization mechanism studies demonstrate that SORgenTAM has an ideal intersystem crossing rate and triplet excited state lifetime for generating O2•- through type-I photochemistry, and the generated O2•- can further trigger a biocascade to reduce the PDT's demand for O2 in an O2-recycble manner. Furthermore, SORgenTAM also serves to activate the AMPK metabolism signaling pathway to inhibit cell repair and promote cell death. Consequently, using this two-step O2-economical strategy, under relatively low light dose irradiation, excellent therapeutic responses toward hypoxic tumors are achieved. This study offers a conceptual while practical paradigm for overcoming the pitfalls of phototherapeutics.

Red Light-Triggered Polyethylene Glycol Deshielding from Photolabile Cyanine-Modified Mesoporous Silica Nanoparticles for On-Demand Drug Release.

PEGylation of drug delivery systems (DDSs) provides a promising approach to overcome the side effect of traditional chemotherapy via the enhanced permeability and retention (EPR) effect, although it further inhibits the internalization behavior of nanocarriers. PEGylation/dePEGylation of the nanocarriers at the desired site exhibits great advantages for nanocarrier-based on-demand drug release. Here, we reported a photoinduced polyethylene glycol (PEG) deshielding nanocarrier, SiO2@DOX-Cy-PEG, for on-demand drug release in an acidic tumor microenvironment. SiO2@DOX nanoparticles were functionalized with PEG-alkyne chains by click reaction with the photolabile cyanine-azide linkers. Under red light irradiation (650 nm), doxorubicin (DOX) can be effectively released from mesoporous silica nanoparticles (MSNs) due to the photolysis of Cy, resulting in the cleavage of the linkers and PEG deshielding in cancer cells. Therefore, SiO2@DOX-Cy-PEG nanoparticles with irradiation arouse a higher cell apoptosis and death ratio, further proving that dePEGylation of MSNs accelerates the release of DOX. In addition, the experiment of the antitumor effect in vivo demonstrated that dePEGylation of the SiO2@DOX-Cy-PEG could effectively promote the therapeutic effect on xenografted 4T1 tumor-bearing BALB/c mice. The results suggested that SiO2@DOX-Cy-PEG was a precisely and remotely on-demand drug delivery system controlled by red light.

Oligo Hyaluronan-Coated Silica/Hydroxyapatite Degradable Nanoparticles for Targeted Cancer Treatment.

Targeted drug delivery systems (TDDSs) provide a promising approach to overcome the side effect of traditional chemotherapy by specific tumor targeting and drug release. Hyaluronan (HA), as a selective CD44 targeting group, has been widely used in TDDSs for chemotherapy. However, different molecular weight HAs would demonstrate different binding ability to CD44, which may result in different therapeutic effects. Herein, a silica/hydroxyapatite (MSNs/HAP) hybrid carrier loaded with anticancer drug doxorubicin (DOX) (DOX@MSNs/HAP) is fabricated. HA and oligo HA (oHA) are coated onto the nanoparticles (HA-DOX@MSNs/HAP, oHA-DOX@MSNs/HAP), respectively, to investigate their performance in tumor targeting ability. oHA-DOX@MSNs/HAP shows much higher efficiency cellular uptake and drug release in tumor regions due to more effective CD44 targeting of oHA. Thus, the anticancer effect of oHA-DOX@MSNs/HAP is significantly enhanced compared to HA-DOX@MSNs/HAP, as demonstrated in a tumor-bearing mouse model. This study may enable the rational design of nanodrug systems for future tumor-targeted chemotherapy.

LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA.

ABSTACT: Conventional therapies and novel molecular targeted therapies against breast cancer have gained great advances over the past two decades. However, poor prognosis and low survival rate are far from expectation for improvement, particularly in patients with triple negative breast cancer (TNBC). Here, we found that lncRNA DANCR was significantly overregulated in TNBC tissues and cell lines compared with normal breast tissues or other type of breast cancer. Knockdown of DANCR suppressed TNBC proliferation both in vitro and in vivo. Further study of underlying mechanisms demonstrated that DANCR bound with RXRA and increased its serine 49/78 phosphorylation via GSK3ß, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis. Taken together, Our findings identified DANCR as an pro-oncogene and uncoverd a new working pattern of lncRNA to mediate TNBC tumorigenesis, which may be a potential therapeutic target for improving treatment of TNBC.

De Novo Design of Phototheranostic Sensitizers Based on Structure-Inherent Targeting for Enhanced Cancer Ablation.

Structure-inherent targeting (SIT) agents are of particular importance for clinical precision medicine; however, there still exists a great lack of SIT phototheranostics for simultaneous cancer diagnosis and targeted photodynamic therapy (PDT). Herein, for the first time, we propose a "one-for-all" strategy by using the Förster resonance energy transfer (FRET) mechanism to construct such omnipotent SIT phototheranostics. Of note, this novel tactic can not only endow conventional sensitizers with highly effective native tumor-targeting potency but also simultaneously improve their photosensitization activities, resulting in dramatically boosted therapeutic index. After intravenous injection of the prepared SIT theranostic, the neoplastic sites are distinctly "lighted up" and distinguished from neighboring tissues, showing a near-infrared signal-to-background ratio value as high as 12.5. More importantly, benefiting from the FRET effect, markedly amplified light-harvesting ability and 1O2 production are demonstrated. Better still, other favorable features are also simultaneously achieved, including specific mitochondria anchoring, augmented cellular uptake (>13-fold), as well as ideal biocompatibility, all of which allow orders-of-magnitude promotion in anticancer efficiency both in vitro and in vivo. We believe this one-for-all SIT platform will provide a new idea for future cancer precision therapy.

Rapidly progressive non-alcoholic fatty liver disease due to hypopituitarism. Report of 5 cases.

BACKGROUND: A few reports had revealed the clinical associations between hypopituitarism and non-alcoholic fatty liver disease (NAFLD). Further evidences were needed. OBJECTIVES: To report 5 cases of young patients with rapidly progressive NAFLD in conjunction with hypopituitarism, aiming to detect the associations. METHODS: Clinical data of the 5 patients were analyzed retrospectively. All had decompensated liver cirrhosis that was finally attributed to NAFLD. Hypopituitarism was a result of pituitary stalk interruption syndrome in 3 patients and craniopharyngioma in 2. RESULTS: 4 patients were overweight (BMI, 24.2 to 28.4kg/m2). All had insulin resistance (HOMA-IR, 4.8 to 7.2). All suffered from at least one metabolic disorder. All had decompensated liver cirrhosis. The average time duration was 6.9 years between the onset of abnormal liver function and decompensated liver cirrhosis. Fatty liver could be detected in all patients. All had anterior hypopituitarism, and 2 also had posterior pituitary dysfunction. The hormone supplements were insufficient. CONCLUSION: Hypopituitarism may be a rare cause of rapidly progressive NAFLD. Insulin resistance and metabolic disorders caused by multiple hormonal deficiencies may contribute to it. Hormone supplement therapy, especially the growth hormone supplement, should be given at the early age to prevent the severe liver disease.