Application of Anchored Instructional Method in Cardiac Surgery ICU Nursing Education.

BACKGROUND: This study investigated the impact of applying the anchored teaching mode with nursing interns on the cardiac surgery intensive care unit (CSICU). METHOD: A total of 110 interns were divided into a control group (taught through traditional methods) and an experimental group (taught using the anchored teaching mode). The anchored mode, emphasizing student-centered learning, included creating scenarios, identifying problems, using self-directed and collaborative learning, and evaluating outcomes. RESULTS: Our study found that the experimental group showed significantly higher scores in emergency response ability, nursing skills, and teaching effectiveness compared with the control group at graduation. CONCLUSION: The findings suggest that implementing the anchored teaching mode can effectively enhance the education of nursing interns on the CSICU, emphasizing the need for further research across different departments and types of hospitals. [J Contin Educ Nurs. 202x;5x(x):xx-xx.].

Construction of a nomogram risk prediction model for prolonged mechanical ventilation in patients following surgery for acute type A aortic dissection.

Background: This study aims to analyze the risk factors associated with prolonged mechanical ventilation (PMV) in patients following surgical treatment for acute type A aortic dissection (ATAAD). The objectives include constructing a predictive model for risk assessment and validating its predictive efficacy. Methods: A total of 452 patients diagnosed with ATAAD and undergoing surgical procedures at a tertiary hospital in Nanjing between January 2021 and April 2023 were selected using a convenience sampling method. Patients were categorized into two groups: PMV group (n = 132) and non-PMV group (n = 320) based on the occurrence of prolonged mechanical ventilation (PMV), and their clinical data were compared. The data were randomly divided into a modeling set and a validation set in a 7:3 ratio. Risk factors for PMV were identified in the modeling group using logistic regression analysis. A risk prediction model was constructed using R 4.1.3 software, visualized via a column chart. Receiver Operating Characteristic (ROC) curves were generated using the validation set to assess model differentiation. Calibration curves were plotted to evaluate accuracy and consistency, and Decision Curve Analysis (DCA) was applied to evaluate clinical utility. Results: The logistic regression analysis identified age, body mass index, preoperative white blood cell count, preoperative creatinine, preoperative cerebral hypoperfusion, and cardiopulmonary bypass time as significant risk factors for postoperative PMV in patients with ATAAD. The area under the curve (AUC) for the validation set ROC curve was 0.856, 95% confidence interval (0.805-0.907), indicating good discrimination. Calibration curves revealed strong alignment with the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated a well-fitted model (P = 0.892). The DCA curve demonstrated a high net benefit value, highlighting the model's strong clinical utility. Conclusions: The risk prediction model developed in this study for PMV in patients undergoing surgery for ATAAD exhibits robust predictive performance. It provides valuable insights for healthcare practitioners in predicting the likelihood of PMV and devising timely and personalized intervention strategies.

Risk factors for postoperative delirium in patients with Stanford type A aortic dissection: a systematic review and meta-analysis.

BACKGROUND: Delirium is a common postoperative complication among patients who undergo Stanford Type A aortic dissection (TAAD). It is associated with increased mortality, as well as other serious surgical outcomes. This study aimed to analyze the risk factors for delirium in TAAD patients. METHODS: Pubmed, Web of science, Embase, the Cochrane Library and CINAHL were searched by computer to collect literatures on risk factors for postoperative delirium (POD) after TAAD. The retrieval period was from the establishment of the database to September 2022. After literature screening, two reviewers independently assessed the quality of the included studies using the Newcastle-Ottawa Scale (NOS). Data were extracted according to standard protocols, and then meta-analysis was performed using Revman 5.3 software. RESULTS: A total of 9 articles, comprising 7 case-control studies and 2 cohort studies, were included in this analysis. The sample size consisted of 2035 patients. POD was associated with increased length of ICU stay (MD 3.24, 95% CI 0.18-6.31, p = 0.04) and length of hospital stay (MD 9.34, 95% CI 7.31-11.37, p < 0.0001) in TAAD patients. Various perioperative risk factors were identified, including age (MD 4.40, 95% CI 2.06-6.73, p = 0.0002), preoperative low hemoglobin levels (MD - 4.44, 95% CI - 7.67 to - 1.20, p = 0.007), body mass index (MD 0.92, 95% CI 0.22-1.63, p = 0.01), history of cardiac surgery (OR 3.06, 95% CI 1.20-7.83, p = 0.02), preoperative renal insufficiency (OR 2.50, 95% CI 1.04-6.04, p = 0.04), cardiopulmonary bypass (CPB) duration (MD 19.54, 95% CI 6.34-32.74, p = 0.004), surgery duration (MD 44.88, 95% CI 5.99-83.78, p = 0.02), mechanical ventilation time (SMD 1.14, 95% CI 0.34-1.94, p = 0.005), acute physiology and chronic health evaluation (APACHE II) score (MD 2.67, 95% CI 0.37-4.98, p = 0.02), postoperative renal insufficiency (OR 2.82, 95% CI 1.40-5.68, p = 0.004), electrolyte disturbance (OR 6.22, 95% CI 3.08-12.54, p < 0.0001) and hypoxemia (OR 3.56, 95% CI 1.70-7.44, p = 0.0007). CONCLUSIONS: POD can prolong ICU stay and hospital stay in TAAD patients. This study identified a number of risk factors for POD after TAAD, suggesting the possibility of early identification of high-risk patients using relevant data.

Analysis of the Influencing Factors of Postoperative Constipation in Patients Undergoing Cardiovascular Surgery: A Cross-Sectional and Prospective Study.

BACKGROUND: The aim of this study was to estimate the potential influencing factors of postoperative constipation in patients undergoing cardiovascular surgery. METHODS: This study included a cohort of 379 patients who underwent cardiovascular surgery at Nanjing Drum Tower Hospital. The patient cohort was stratified into two groups based on the presence or absence of postoperative constipation. Utilizing logistic regression analysis, both univariate and multivariate analyses were conducted to elucidate the factors influencing defecation problems. The predictive accuracy of the findings was subsequently evaluated through the receiver operating characteristic (ROC) curve. RESULTS: Among the cohort of 379 patients subjected to cardiovascular surgery, a noteworthy 20.8% (n = 79) reported incidences of postoperative defecation issues. A multivariate logistic regression analysis showed that age (odds ratio (OR) = 1.063, 95% confidence interval (CI) 1.034-1.097, p < 0.001), operation time (OR = 1.004, 95% CI: 1.000-1.008, p = 0.028), ventilator usage time (OR = 1.032, 95% CI: 1.010-1.055, p = 0.004), polypharmacy (OR = 2.134, 95% CI: 1.069-4.321, p = 0.032), use of cough medicine (OR = 2.981, 95% CI: 1.271-6.942, p = 0.011) and psychological or behavioral barriers to defecation in the hospital environment (OR = 31.039, 95% CI: 14.313-73.179, p < 0.001) were independent risk factors for postoperative constipation in patients undergoing cardiovascular surgery. The area under the curve (AUC) for predicting postoperative constipation was 0.885. CONCLUSION: In the pursuit of optimizing postoperative recovery and mitigating postoperative constipation incidence, a targeted approach is imperative. Specifically, a focused intervention directed towards elderly patients, extended operation and prolonged ventilator durations, polypharmacy regimens, use of cough medicine, and those with psychological or behavioral barriers to defecation within the hospital milieu emerges as pivotal.

New-Onset Post-Operative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting Surgery - A Retrospective Case-Control Study

ABSTRACT Introduction: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. Objective: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. Methods: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. Results: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. Conclusion: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.

New-Onset Post-Operative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting Surgery - A Retrospective Case-Control Study.

INTRODUCTION: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. OBJECTIVE: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. METHODS: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. RESULTS: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. CONCLUSION: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.

Deep sternal wound infection and pectoralis major muscle flap reconstruction: A single-center 20-year retrospective study.

Background: One of the most drastic complications of median sternal incision is deep sternal wound infection (DSWI), as it can lead to prolonged hospitalization, increased expected costs, re-entry into the ICU and even reoperation. Since the pectoralis major muscle flap (PMMF) technique was proposed in the 1980s, it has been widely used for sternal reconstruction after debridement. Although numerous studies on DSWI have been conducted over the years, the literature on DSWI in Chinese population remains limited. The purpose of this study was to investigate the clinical characteristics of DSWI in patients and the clinical effect of the PMMF at our institution. Methods: This study retrospectively analyzed all 14,250 consecutive patients who underwent cardiac surgery in the Department of Cardiothoracic Surgery of Drum Tower Hospital from 2001 to 2020. Ultimately, 134 patients were diagnosed with DSWI.,31 of whom had recently undergone radical debridement and transposition of the PMMF in the cardiothoracic surgery or burns and plastic surgery departments because of DSWIs, while the remaining patients had undergone conservative treatment or other methods of dressing debridement. Results: In total, 9,824 patients were enrolled in the study between 2001 and 2020, of whom 134 met the DSWI criteria and 9690 served as controls. Body mass index (OR = 1.08; P = 0.02; 95% CI, 1.01∼1.16) and repeat sternotomy (OR = 5.93; P < 0.01; 95% CI, 2.88∼12.25) were important risk factors for DSWI. Of the 134 patients with DSWI, 31 underwent the PMMF technique, and the remaining 103 served as controls. There were significant differences in coronary artery bypass grafting (CABG) (P < 0.01), valve replacement (P = 0.04) and repeat sternotomy (P < 0.01) between the case group and the control group. The postoperative extubation time (P < 0.001), ICU time (P < 0.001), total hospitalization time (P < 0.001) and postoperative hospitalization time (P < 0.001) in the PMMF group were significantly lower than those in the control group. The results of multivariate regression analysis showed that PMMF surgery was an important protective factor for the postoperative survival of DSWI patients (OR = 0.12; P = 0.04; 95% CI, 0.01∼0.90). Conclusions: Staphylococcus aureus was the most common bacteria causing DSWI, which was associated with BMI and reoperation, and can be validly treated with PMMF.

Different cerebral functional segregation in Sjogren's syndrome with or without systemic lupus erythematosus revealed by amplitude of low-frequency fluctuation.

BACKGROUND: Sjögren's syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity. PURPOSE: To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF). MATERIAL AND METHODS: Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation. RESULTS: ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE. CONCLUSION: SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Headache frequency associates with brain microstructure changes in patients with migraine without aura.

Neuroimaging studies have implicated abnormal brain microstructure in episodic migraine (EM), but whether the pattern is altered during migraine chronification is not well known. Fifty-six patients with migraine without aura, including 39 EM patients and 17 chronic migraine (CM) patients, and 35 healthy controls (HCs) were enrolled. Voxel-based morphometry analysis was performed to assess gray matter (GM) volume differences among groups and their association with clinical feature was examined. Compared with the HC group, both migraine groups showed increased GM volume in the periaqueductal grey matter (PAG) and decreased GM volume in the anterior cingulate cortex (ACC). The left hippocampus/parahippocampal gyrus (PHG) volume of the HC group was smaller than that of the EM group, but was larger than that of the CM group. For the dorsolateral prefrontal cortex (dlPFC), the EM group showed the smallest GM volume while the CM group had the largest volume. Higher headache frequency was associated with greater GM volume in the PAG and dlPFC, but was associated with smaller GM volume in the ACC and hippocampus/PHG across all patients. GM volume changes in regions involved in pain generation and control are potential neural mechanism underlying migraine, and are associated with migraine types and headache frequency.

Altered local and distant functional connectivity density in chronic migraine: a resting-state functional MRI study.

PURPOSE: Previous studies have indicated disrupted functional connectivity in multiple brain regions and resting-state networks in episodic migraine, but it is unclear how brain network property is disrupted in chronic migraine. METHODS: Using resting-state functional magnetic resonance imaging and voxel-wise functional connectivity density analysis, we examined the large-scale functional connectivity pattern over the whole brain in 17 patients with chronic migraine without medication overuse compared to 35 healthy controls. The associations between functional connectivity density and clinical variables were also explored. RESULTS: Compared with controls, chronic migraine patients showed decreased local and distant functional connectivity density in the dorsolateral and medial prefrontal cortexes and precuneus and increased local and distant functional connectivity density in the hippocampal complex. The patients also presented increased local functional connectivity density in the orbital frontal gyrus and cerebellum and increased distant functional connectivity density in the temporal pole. Moreover, local functional connectivity density in several brain regions, such as the left superior temporal gyrus and dorsal anterior cingulate cortex, was found to be correlated with headache frequency or pain intensity. CONCLUSION: Chronic migraine is associated with functional connectivity alterations in regions involved in multisensory integration, affective and cognitive processing, and pain modulation. Both local and distant functional connectivity density are complementary biomarkers for investigating the neural mechanism of this disorder. Some local functional connectivity density alterations may be useful for assessing the disease burden of chronic migraine.

Functional Alterations in the Posterior Insula and Cerebellum in Migraine Without Aura: A Resting-State MRI Study.

Background: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis. Methods: Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach. Results: Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC. Conclusion: Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.

Dynamics and Concordance Abnormalities Among Indices of Intrinsic Brain Activity in Individuals With Subjective Cognitive Decline: A Temporal Dynamics Resting-State Functional Magnetic Resonance Imaging Analysis.

Individuals with subjective cognitive decline (SCD) are more likely to develop into Alzheimer disease (AD) in the future. Resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown alterations of intrinsic brain activity (IBA) in SCD individuals. However, rs-fMRI studies to date have mainly focused on static characteristics of IBA, with few studies reporting dynamics- and concordance-related changes in IBA indices in SCD individuals. To investigate these aberrant changes, a temporal dynamic analysis of rs-fMRI data was conducted on 94 SCD individuals (71.07 ± 6.18 years, 60 female), 75 (74.36 ± 8.42 years, 35 female) mild cognitive impairment (MCI) patients, and 82 age-, gender-, and education-matched controls (NCs; 73.88 ± 7.40 years, 49 female) from the Alzheimer's Disease Neuroimaging Initiative database. The dynamics and concordance of the rs-fMRI indices were calculated. The results showed that SCD individuals had a lower amplitude of low-frequency fluctuations dynamics in bilateral hippocampus (HP)/parahippocampal gyrus (PHG)/fusiform gyrus (FG) and bilateral cerebellum, a lower fractional amplitude of low-frequency fluctuation dynamics in bilateral precuneus (PreCu) and paracentral lobule, and a lower regional homogeneity dynamics in bilateral cerebellum, vermis, and left FG compared with the other two groups, whereas those in MCI patients were higher (Gaussian random field-corrected, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, SCD individuals had higher concordance in bilateral HP/PHG/FG, temporal lobe, and left midcingulate cortex than NCs, but those in MCI were lower than those in NCs. No correlation between concordance values and neuropsychological scale scores was found. SCD individuals showed both dynamics and concordance-related alterations in IBA, which indicates a compensatory mechanism in SCD individuals. Temporal dynamics analysis offers a novel approach to capturing brain alterations in individuals with SCD.

Timely coordinated phototherapy mediated by mesoporous organosilica coated triangular gold nanoprisms.

A variety of nanocarriers have been designed to deliver photosensitizers (PSs) and promote the clinical applications of photodynamic therapy (PDT). However, most of them suffer from insufficient loading capability, premature leakage, and/or unstable therapeutic efficacy. Herein, we constructed a novel nanocomposite (TGP@MOS) with a benzene-bridged mesoporous organosilica shell and a triangular gold nanoprism core. The TGP@MOS could load model PS molecules, zinc phthalocyanine (ZnPc), with high loading capacity (11.8 wt%) and minimal premature leakage (only 2.6% after incubation in PBS with 10% FBS for 60 h) viaπ-π stacking interactions and hydrophobic interactions. We demonstrated that the obtained TGP@MOS-ZnPc could realize timely coordinated photodynamic/photothermal therapy upon single irradiation, and thus stabilize and maximize the therapeutic efficacy of phototherapy both in vitro and in vivo. Other advantages of TGP@MOS-ZnPc include excellent water solubility, stability, hemocompatibility and biocompatibility.

High and low molecular weight hyaluronic acid-coated gold nanobipyramids for photothermal therapy.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is known that hyaluronic acid (HA) binds CD44 receptors, which are overexpressed on the surface of TNBC cells. To optimize the targeting ability of HA, in this study we coated gold nanobipyramids (GBPs) with high and low molecular weight HA (380 kDa and 102 kDa), named GBPs@h-HA and GBPs@l-HA, respectively. GBPs@l-HA and GBPs@h-HA had excellent stability when dispersed in water and PBS (pH 7.4) for seven days. The HA density was calculated by the ratio of HA to GBPs@l-HA and GBPs@h-HA, which was 13.22 and 4.77, respectively. The two nanoparticles displayed good photostability, which was evaluated by their photothermal performance and similar biocompatibility. Inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed superior cellular uptake of GBPs@h-HA over GBPs@l-HA. Upon 808 nm laser irradiation, the GBPs@h-HA also showed higher therapeutic efficacy than GBPs@l-HA both in vitro and in vivo. Overall, our study demonstrates that the molecular weight of HA plays an important role in the targeting ability and thus photothermal therapeutic efficacy of HA-coated gold nanobipyramids.

Tumor Acidic Microenvironment Targeted Drug Delivery Based on pHLIP-Modified Mesoporous Organosilica Nanoparticles.

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.

Effect of histone modifications on hMLH1 alternative splicing in gastric cancer.

hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10-11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines. Lower level of H4K16ac and H3ac was detected in hMLH1 exon 10-11 region in gastric cancer cell lines when compared with human gastric mucosal epithelial cell line GES-1. A significant decrease of hMLH1 delEx11 and delEx10-11 was observed in gastric cancer cell lines after trichostatin A treatment. H3K36me3 and H3K4me2 levels were lower in hMLH1 exon 10-11 and exon 16-17 regions in gastric cancer lines when compared with GES-1. Aberrant transcripts such as hMLH1 delEx11 and delEx10-11 were significantly higher in gastric cancer cell lines after small interfering RNA-mediated knockdown of SETD2 (the specific methyltransferase of H3K36). The hMLH1 delEx10 and delEx10-11 transcripts were increased after interference of SRSF2. Taken together, our study demonstrates that lower level of histone acetylation and specific histone methylation such as H3K36me3 correlate with aberrant transcripts in hMLH1 exon 10-11 region. SRSF2 may be involved in these specific exons skipping as well.

Periodic Mesoporous Organosilica Coated Prussian Blue for MR/PA Dual-Modal Imaging-Guided Photothermal-Chemotherapy of Triple Negative Breast Cancer.

Complete eradication of highly aggressive triple negative breast cancer (TNBC) remains a notable challenge today. In this work, an imaging-guided photothermal-chemotherapy strategy for TNBC is developed for the first time based on a periodic mesoporous organosilica (PMO) coated Prussian blue (PB@PMO) nanoplatform. The PB@PMOs have organic-inorganic hybrid frameworks, uniform diameter (125 nm), high surface area (866 m2 g-1), large pore size (3.2 nm), excellent photothermal conversion capability, high drug loading capacity (260 µg mg-1), and magnetic resonance (MR) and photoacoustic (PA) imaging abilities. The MR and PA properties of the PB@PMOs are helpful for imaging the tumor and showing the accumulation of the nanoplatform in the tumor region. The bioluminescence intensity and tumor volume of the MDA-MB-231-Luc tumor-bearing mouse model demonstrate that TNBC can be effectively inhibited by the combined photothermal-chemotherapy than monotherapy strategy. Histopathological analysis further reveals that the combination therapy results in most extensive apoptotic and necrotic cells in the tumor without inducing obvious side effect to major organs.

Synergistic Chemo-Photothermal Therapy of Breast Cancer by Mesenchymal Stem Cell-Encapsulated Yolk-Shell GNR@HPMO-PTX Nanospheres.

Mesenchymal stem cells (MSCs) have attracted increasing attention as vehicles for cancer treatment. Herein, MSC-based synergistic oncotherapy strategy is presented for the first time. To achieve this goal, yolk-shell structured gold nanorod embedded hollow periodic mesoporous organosilica nanospheres (GNR@HPMOs) with high paclitaxel (PTX) loading capability and excellent photothermal transfer ability upon near-infrared (NIR) light irradiation are first prepared. Cytotoxicity and migration assays show that the viability and tumor-homing capability of MSCs are well-retained after internalization of high content of PTX loaded GNR@HPMOs (denoted as GNR@HPMOs-PTX). In vitro experiments show the GNR@HPMOs-PTX loaded MSCs (GNR@HPMOs-PTX@MSCs) possess synergistic chemo-photothermal killing effects for breast cancer cells. Also, photoacoustic imaging shows that the MSCs can improve dispersion and distribution in tumor tissue for GNR@HPMOs-PTX after intratumoral injection. In vivo experiments in breast cancer model of nude mice further demonstrate that the GNR@HPMOs-PTX@MSCs significantly inhibit tumor growth, suggesting their great potential for synergistic therapy of cancer.

Smart Cancer Cell Targeting Imaging and Drug Delivery System by Systematically Engineering Periodic Mesoporous Organosilica Nanoparticles.

The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24 h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.

NIR photoresponsive drug delivery and synergistic chemo-photothermal therapy by monodispersed-MoS2-nanosheets wrapped periodic mesoporous organosilicas.

Two-dimensional (2D) MoS2 nanosheets have attracted increasing attention in recent years owing to their various fascinating properties, particularly excellent near-infrared (NIR) photothermal feature. In this study, we synthesized a novel NIR-light-triggered drug-delivery system by wrapping MoS2 nanosheets around doxorubicin (Dox)-loaded periodic mesoporous organosilicas (PMOs) and then decorating with polyethylene glycol (PEG) to form a PMO-Dox@MoS2-PEG nanoplatform for the first time. The obtained PMO-Dox@MoS2-PEG nanoplatforms had a uniform diameter (326 nm), high Dox loading capacity (160 µg mg-1 PMOs), excellent photothermal transformation ability, and good dispersibility in physiological conditions. Note that the Dox was almost completely blocked in the PMO-Dox@MoS2-PEG nanoplatforms, and the photothermal effect of the MoS2 nanosheets could efficiently trigger the release of Dox under an 808 nm laser irradiation. Simultaneously, the PMO-Dox@MoS2-PEG nanoplatforms realized a combined chemotherapy and photothermal therapy for liver cancer cells and breast cancer cells upon NIR laser irradiation. Compared with the single photothermal therapy or chemotherapy, the combined treatment had an improved synergistic therapeutic efficacy. We believe the NIR-light-triggered drug-delivery system with synergistic chemo-photothermal therapeutic property provides a promising strategy for cancer treatment.