Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients.

BACKGROUND: Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. METHODS: Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. RESULTS: The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013-0.915). CONCLUSION: Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

A nomogram model for predicting lower extremity deep vein thrombosis after gynecologic laparoscopic surgery: a retrospective cohort study.

Objective: To investigate the risk factors associated with lower extremity deep vein thrombosis (LEDVT) and to establish a predictive model for patients who undergo gynecologic laparoscopic surgery. Methods: A review of clinical data was conducted on patients who underwent gynecologic laparoscopic surgery between November 1, 2020, and January 31, 2022. Patients who developed LEDVT after surgery were included as the observation group, while the control group comprised patients who did not experience complications. Multivariate forward stepwise logistic regression models were used to identify independent risk factors associated with LEDVT. A nomogram model was then developed based on these risk factors. Results: A total of 659 patients underwent gynecologic laparoscopic surgery during the study period, and 52 (7.89%) of these patients developed postoperative LEDVT. Multivariate logistic regression analysis showed that older age (adjusted OR, 1.085; 95% CI [1.034-1.138]; P < 0.05), longer operation duration (adjusted OR, 1.014; 95% CI [1.009-1.020]; P < 0.05), shorter activated partial thromboplastin time (APTT) (adjusted OR, 0.749; 95% CI [0.635-0.884]; P < 0.05), higher D-dimer (adjusted OR, 4.929; 95% CI [2.369-10.255]; P < 0.05), higher Human Epididymis Protein 4 (HE4) (adjusted OR, 1.007; 95% CI [1.001-1.012]; P < 0.05), and history of hypertension (adjusted OR, 3.732; 95% CI [1.405-9.915]; P < 0.05) were all independent risk factors for LEDVT in patients who underwent gynecologic laparoscopic surgery. A nomogram model was then created, which had an area under the curve of 0.927 (95% CI [0.893-0.961]; P < 0.05), a sensitivity of 96.1%, and a specificity of 79.5%. Conclusions: A nomogram model that incorporates information on age, operation duration, APTT, D-dimer, history of hypertension, and HE4 could effectively predict the risk of LEDVT in patients undergoing gynecologic laparoscopic surgery, potentially helping to prevent the development of this complication.

Improving the Sustainability of Processing By-Products: Extraction and Recent Biological Activities of Collagen Peptides.

Society and consumers are increasingly concerned about food safety and the sustainability of food production systems. A significant amount of by-products and discards are generated during the processing of aquatic animals, which still needs to be fully utilized by the food industry. The management and sustainable use of these resources are essential to avoiding environmental pollution and resource waste. These by-products are rich in biologically active proteins, which can be converted into peptides by enzymatic hydrolysis or fermentation treatment. Therefore, exploring the extraction of collagen peptides from these by-products using an enzymatic hydrolysis technology has attracted a wide range of attention from numerous researchers. Collagen peptides have been found to possess multiple biological activities, including antioxidant, anticancer, antitumor, hypotensive, hypoglycemic, and anti-inflammatory properties. These properties can enhance the physiological functions of organisms and make collagen peptides useful as ingredients in food, pharmaceuticals, or cosmetics. This paper reviews the general methods for extracting collagen peptides from various processing by-products of aquatic animals, including fish skin, scales, bones, and offal. It also summarizes the functional activities of collagen peptides as well as their applications.

Clinical relevance of serum lipids in the carcinogenesis of oral squamous cell carcinoma.

BACKGROUND: Dyslipidaemia is associated with cancers. However, the specific expression of serum lipids in oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) remains unclear, and it remains unknown whether serum lipids are associated with the development of OPMD and OSCC. This study investigated the serum lipid profiles of OPMD and OSCC patients, and the association of serum lipids with the occurrence of OPMD and OSCC. METHODS: A total of 532 patients were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Serum lipid parameters including total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo-A), apolipoprotein B (Apo-B), and lipoprotein (a) (Lpa) were analysed, and clinicopathological data were collected for further analysis. Furthermore, a regression model was used to evaluate the relationship between serum lipids and the occurrence of OSCC and OPMD. RESULTS: After adjusting for age and sex, no significant differences were observed in serum lipid or body mass index (BMI) between OSCC patients and controls (P > 0.05). HDL-C, Apo-A, and Apo-B levels were lower in OSCC patients than in OPMD patients (P < 0.05); HDL-C and Apo-A levels were higher in OPMD patients than in controls (P < 0.05). Furthermore, female OSCC patients had higher Apo-A and BMI values than males. The HDL-C level was lower in patients under 60 years of age than in elders (P < 0.05); and age was related to a higher risk of developing OSCC. Female patients with OPMD had higher TC, HDL-C, and Apo-A levels than males (P < 0.05); OPMD patients over 60 years of age had higher HDL-C than youngers (P < 0.05), whereas the LDL-C level was lower in elders (P < 0.05). The HDL-C and BMI values of the patients with oral leukoplakia (OLK) with dysplasia were more elevated than those of the oral lichen planus group, and the LDL-C, and Apo-A levels in patients with OLK with dysplasia were decreased (P < 0.05). Sex, high HDL-C and Apo-A values were associated with the development of OPMD. CONCLUSION: Serum lipids exhibited certain differences according to the occurrence and development of OSCC; high levels of HDL-C and Apo-A might be markers for predicting OPMD.

Photoacoustic/fluorescence dual-modality cyanine-based probe for real-time imaging of endogenous cysteine and in situ diagnosis of cervical cancer in vivo.

Cysteine (Cys), one of cellular biothiols in the organism, is associated with many diseases, such as Parkinson's disease, Alzheimer's disease, liver damage, rheumatoid arthritis, and cancer. However, activatable fluorescence/photoacoustic (FL/PA) probes for non-invasive, real-time, and deep imaging of Cys in vivo are still lacking, and this hinders the diagnosis of Cys-related diseases. Herein, we designed and synthesized a novel activated FL/PA dual-modality cyanine-base probe (FP700) for real-time detection of Cys. The probe FP700 was established with near-infrared emissive dye cyanin as the fluorophore, linking with 2, 4-dinitrobenzenesulfonyl group as the recognition moiety for Cys. Using the FP700, we found that the FP700 exhibited intensive "turn-on" FL/PA signals under the excitation of 700 nm, which realized noninvasive in vivo detection of exogenous Cys. Significantly, FP700 accurately detected endogenous Cys though the FL/PA dual-mode imaging technology in tumor-bearing mice and obtain 3D PA diagnostic images with deep penetration depth and spatial resolution. Thus, the new dual-modality probe FP700 has advantage of high potential for deep tumor diagnosis of Cys in vivo, which may provide a new approach for the detection of cervical cancer and identification of its potential therapeutic targets.

Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen-glucose deprivation and reoxygenation.

Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen-glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes' protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.

Diffusion-Weighted Imaging Combined with Perfusion-Weighted Imaging under Segmentation Algorithm in the Diagnosis of Melanoma.

This study is aimed at exploring the value of magnetic resonance diffusion-weighted imaging (DWI) combined with perfusion-weighted imaging (PWI) for diagnosing melanoma under a three-dimensional (3D) hybrid segmentation algorithm. 40 patients with melanoma were collected as research objects and subjected to magnetic resonance imaging (MRI) examination. A segmentation model was constructed and the original images were input. The noise contained in the images was preprocessed and normalized, and the mixed level set segmentation was performed after linear fusion of the images. Imaging findings were analyzed to find that the combined diagnosis of DWI and PWI with a 3D hybrid segmentation algorithm had the advantage of being clear and accurate. 10 primary cases were detected, which occurred in the cerebral meninges; 30 cases of metastases occurred inside the skull, mostly adjacent to the surface of the brain. The typical T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) of melanoma showed high signal and low signal, respectively, and the enhanced scan showed obvious enhancement. Atypical melanoma was manifested variously in MRI; a few had cystic necrosis, and an enhanced scan of the solid area revealed significant enhancement. Patients with multiple metastatic melanomas mainly showed low signal on DWI, and patients with primary or single metastatic melanoma mainly showed high signal or mixed high signal. Patients with perfusion imaging showed high perfusion on PWI. The 3D hybrid segmentation algorithm helped to improve the accuracy of DWI combined with PWI in the diagnosis of melanoma. This work provided a certain reference for the clinical diagnosis of melanoma.

BF2 group chelated AIE fluorescent probe for polarity mapping of lipid droplets in cells and in vivo.

Lipid droplets (LDs), are multi-functional organelles with the storage of neutral lipids and proteins, participating in various of physiological processes. However, abnormal of LDs in morphology and numbers always lead to multiple diseases, including cancer, viral infection, obesity, inflammation. To better understand the physiological function of LDs in living cells, we designed two new fluorescent probes LDs-CA and LDs-BCA based on the triphenylamine and coumarin fluorophores to monitor LDs polarity and numbers variation in this work. The one-step strategy for the regulation of BF2 group realized a gratifying in emission wavelengths from orange fluorescence of LDs-CA to the red fluorescence of LDs-BCA, surprisingly. The two novel probes showed strong positive solvatochromism effect in different solvents and exhibited the aggregation-induced emission (AIE) effect. Based on the above excellent optical properties, LDs-CA and LDs-BCA were applied for imaging of the LDs with high overlap coefficient when co-stained with commercial dyes, respectively. The probes of LDs-CA and LDs-BCA provided an intuitive method to visualize the dynamic changes of LDs in morphology, size, and numbers under nutritionalstimulation, affording a powerful tool for fluorescence visualization of LDs related biological processes. Notably, the near-infrared emissive probe LDs-BCA successfully imaged the gastric fat in living obese mouse, which may provide a new idea for medical diagnostics.

A non-peptide probe for detecting chymotrypsin activity based on protection-deprotection strategy in living systems.

Chymotrypsin (CHT) plays a vital role in the metabolism of organisms and affects cell proliferation and apoptosis. Abnormal levels of CHT will lead to a variety of diseases, such as inflammatory arthritis, diabetes, pharyngitis, indigestion, and pancreatic cancer. Therefore, it is significant to design an effective method for the detection of CHT in living systems. Here, we synthesized a specific deep-red non-peptide probe DT by effectively combining isophorone and p-hydroxybenzaldehyde for the detection of CHT using 3-phenylpropionate chloride as the recognition group based on a protection-deprotection strategy. The DT probe exhibited an emission range of 525-700 nm and showed excellent photostability, high sensitivity (LOD = 0.071 U mL-1), and selectivity for CHT detection. The cellular experiments demonstrated that DT could sensitively recognize CHT activity in three cell lines and the content of CHT was much higher in P815 cells than in MCF-7 and 3T3 cells. Also, DT was successfully used to visualize the endogenous CHT in zebrafish. Notably, the DT probe provided an intuitive way to visualize endogenous CHT in mouse pancreas for the first time, demonstrating the potential for application in the future clinical diagnosis of pancreatic diseases. Therefore, the small-molecule probe DT is expected to be a useful molecular tool for CHT-related disease diagnosis and drug discovery.

Nanotechnology-based immunotherapies to combat cancer metastasis.

Emerging concepts in nanotechnology have gained particular attention for their clinical translation of immunotherapies of cancer, autoimmune and infectious diseases. Several nanoconstructs have been engineered with unique structural, physicochemical, and functional features as robust alternatives for conventional chemotherapies. Traditional cancer therapies like chemotherapy, radiotherapy, and ultimately surgery are the most widely practiced in biomedical settings. Biomaterials and nanotechnology have introduced vehicles for drug delivery and have revolutionized the concept of the modern immunotherapeutic paradigm. Various types of nanomaterials, such as nanoparticles and, more specifically, drug-loaded nanoparticles are becoming famous for drug delivery applications because of safety, patient compliance, and smart action. Such therapeutic modalities have acknowledged regulatory endorsement and are being used in twenty-first-century clinical settings. Considering the emerging concepts and landscaping potentialities, herein, we spotlight and discuss nanoparticle-based immunotherapies as a smart and sophisticated drug delivery approach to combat cancer metastasis. The introductory part of this manuscript discusses a broad overview of cancer immunotherapy to understand better the tumor microenvironment and nanotechnology-oriented immunomodulatory strategies to cope with advanced-stage cancers. Following that, most addressable problems allied with conventional immunotherapies are given in comparison to nanoparticle-based immunotherapies. The later half of this work comprehensively highlights the requisite delivery of various bioactive entities with particular cases and examples. Finally, this review also encompasses a comprehensive concluding overview and future standpoints to strengthen a successful clinical translation of nanoparticle-based immunotherapies as a smart and sophisticated drug delivery approach.

Network Pharmacology for Analyzing the Key Targets and Potential Mechanism of Wogonin in Gliomas.

Objective: To analyze the key targets and potential mechanisms underlying the volatile components of Scutellaria baicalensis Georgi acting on gliomas through network pharmacology combined with biological experiments. Methods: We have extracted the volatile components of Scutellaria baicalensis by gas chromatography-mass spectrometry (GC-MS) and determined the active components related to the onset and development of gliomas by combining the results with the data from the Traditional Chinese Medicine Systems Pharmacology database. We screened the same targets for the extracted active components and gliomas through network pharmacology and then constructed a protein-protein interaction network. Using a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we analyzed the protein effects and regulatory pathways of the common targets. Lastly, we employed ELISA and Western blot in verifying the key targets in the regulatory pathway. Results: We ultimately determined that the active component in S. baicalensis Georgi related to the onset and development of gliomas was Wogonin. The results of the network pharmacology revealed 85 targets for glioma and Wogonin. We used gene ontology to analyze these target genes and found that they involved 30 functions, such as phosphatidylinositol phosphokinase activation, while the KEGG analysis showed that there were 10 regulatory pathways involved. Through the following analysis, we found that most of the key target genes are distributed in the PI3K-Akt and interleukin 17 signaling pathways. We then cultured U251 glioma cells for the experiments. Compared with the control group, no significant change was noted in the caspase-3 expression; however, cleaved caspase-3 expression increased significantly and was dose-dependent on Wogonin. The expression of Bad and Bcl-2 with 25 µM of Wogonin has remained unchanged, but when the Wogonin dose was increased to 100 µM, the expression of Bad and Bcl-2 was noted to change significantly (Bad was significantly upregulated, while Bcl-2 was significantly downregulated) and was dose-dependent on Wogonin. The ELISA results showed that, compared with the control group, the secretion of tumor necrosis factor alpha, IL-1ß, and IL-6 decreased as the Wogonin concentration increased. Tumor necrosis factor alpha downregulation had no significant dose-dependent effect on Wogonin, the inhibitory effect of 25 µM of Wogonin on IL-6 was not significant, and IL-1ß downregulation had a significant dose-dependent effect on Wogonin. Conclusion: Wogonin might promote the apoptosis of glioma cells by upregulating proapoptotic factors, downregulating antiapoptotic factors, and inhibiting the inflammatory response, thereby inhibiting glioma progression.

Synthesis, molecular docking calculation, fluorescence and bioimaging of mitochondria-targeted ratiometric fluorescent probes for sensing hypochlorite in vivo.

Mitochondria are the main sites for the production of hypochlorite (OCl-). The protein adenine nucleotide translocase (ANT) is located in the inner mitochondria membrane, which is mainly participated in the transportation of ions and metabolites. At the cellular organelle level, overexpression of ANT is associated with enhanced production of OCl-, however, abnormal levels of OCl- cause redox imbalance and loss of function of mitochondria. Herein, a novel mitochondria-targeted ratiometric fluorescent probe Mi-OCl-RP has been developed. Molecular docking calculation suggested a potential molecular target for the probe in the ANT, and the high binding energy (-8.58 kcal mol-1) may explain the high mitochondria selectivity of Mi-OCl-RP. The unique probe exhibits excellent spectral properties including ratiometric fluorescence response signals to OCl- (within 7 s), high selectivity and sensitivity, and a large Stokes shift (278 nm). In addition, the colocalization coefficient confirms that Mi-OCl-RP can effectively target mitochondria. Furthermore, Mi-OCl-RP has low toxicity and good permeability, and was successfully employed in ratiometric imaging of OCl-in vivo, affording a robust molecular tool for investigating the biological functions of OCl- in living systems.

A fluorescent probe for specific detection of ß-galactosidase in living cells and tissues based on ESIPT mechanism.

ß-galactosidase is of great significance to living organisms, which is an important marker of primary ovarian cancer and cellular senescence. To detect the activity of ß-galactosidase, a novel fluorescent probe ESIPT-GAL which based on excited state intramolecular proton transfer (ESIPT) mechanism for detecting ß-galactosidase is developed in this work with low background fluorescence and high sensitivity (ΦF = 0.0045-0.2409). The fluorescence intensity at 552 nm of this probe increased by ~ 55 times with ß-galactosidase addition (0-4 U/mL), and its detection limit is very low (3.9 × 10-5 U/mL). In addition, the spectral data (pseudo-first-order rate: 1.303 min-1) and enzyme kinetic parameter (Vmax = 69.5 µΜ•S-1) both show that the probe can achieve rapid response to ß-galactosidase. Moreover, the probe has good water solubility, which ensures that it has good biocompatibility and can be easily applied to detect ß-galactosidase in living cells and tissues. Importantly, the probe ESIPT-GAL can monitor ß-galactosidase in deep mouse tissue sections (90 µm).

Ratiometric Fluorescence Imaging for the Distribution of Nucleic Acid Content in Living Cells and Human Tissue Sections.

The misregulation of nucleic acids behavior leads to cell dysfunction and induces serious diseases. A ratiometric fluorescence probe is a powerful tool to study the dynamic behavior and function relationships of nucleic acids. However, currently, no such effective probe has been reported for in situ, real-time tracking of nucleic acids in living cells and tissue sections. Herein, the unique probe named QPP-AS was rationally designed for ratiometric fluorescence response to nucleic acids through skillful regulation of the intramolecular charge-transfer capabilities of the electron acceptor and donor. Encouraged by the advantages of the selective nucleic acid response, ideal biocompatibility, and high signal-to-noise ratio, QPP-AS has been applied for in situ, real-time ratiometric fluorescence imaging of nucleic acids in living cells for the first time. Furthermore, we have demonstrated that QPP-AS is capable of visualizing the dynamic behavior of nucleic acids during different cellular processes (e.g., cell division and apoptosis) by ratiometric fluorescence imaging. More significantly, QPP-AS has been successfully used for ratiometric fluorescence imaging of nucleic acids in human tissue sections, which provides not only the cell contour, nuclear morphology, and nuclear-plasma ratio but also the nucleic acid content information and may greatly improve accuracy in clinicopathological diagnosis.

Tyrosine kinase inhibitors and their unique therapeutic potentialities to combat cancer.

Cancer is one of the leading causes of death with a mortality rate of 12%. Although significant progress has been achieved in cancer research, the effective treatment of cancer remains the greatest global challenge in medicine. Dysregulation of tyrosine kinases (TK) is one of the characteristics of several types of cancers. Thus, drugs that target and inhibit these enzymes, known as TK inhibitors (TKIs), are considered vital chemotherapeutics to combat various types of cancer. The oral bioavailability of available TKIs and their targeted therapy are their potential benefits. Based on these characteristics, most TKIs are included in first/second-line therapy for the treatment of different cancers. This review aims to shed light on orally-active TKIs (natural and synthetic molecules) and their promising implication in the therapy of numerous types of tumors along with their mechanisms of action. Further, recent progress in the development of synthetic and isolation of natural TKIs is reviewed. A significant growth in research regarding the development of new-generation TKIs is made with time (23 FDA-approved TKIs from 2018) due to their better therapeutic response. Oral bioavailability should be considered as an important parameter while developing of new-generation TKIs; however, drug delivery systems can also be used to address issue of poor bioavailability to a certain extent. Moreover, clinical trials should be designed in consideration of the development of resistance and tumor heterogeneity.

Amphiphilic block polymer-based self-assembly of high payload nanoparticles for efficient combinatorial chemo-photodynamic therapy.

Combinatorial chemo-photodynamic therapy is regared as effective cancer therapy strategy, which could be realized via multiple nano-drug delivery system. Herein, novel high payload nanoparticles stabilized by amphiphilic block polymer cholesterol-b-poly(ethylene glycol) (PEG)2000 (Chol-PEG2000) were fabricated for loading chemotherapeutic drug 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6). The obtained HCPT/Ce6 NPs showed uniform rod-like morphology with a hydration diameter of 178.9 ± 4.0 nm and excellent stability in aqueous solution. HCPT and Ce6 in the NPs displayed differential release profile, which was benefit for preferentially exerting the photodynamic effect and subsequently enhancing the sensitivity of the cells to HCPT. Under laser irradiation, the NPs demonstrated fantastic in vitro and in vivo anticancer efficiency due to combinational chemo-photodynamic therapy, enhanced cellular uptake effectiveness, and superb intracellular ROS productivity. Besides, the NPs were proved as absent of systemic toxicity. In summary, this nanoparticle delivery system could be hopefully utilized as effective cancer therapy strategy for synergistically exerting combined chemo-photodynamic therapy in clinic.

Preparation of robust fluorescent probes for tracking endogenous formaldehyde in living cells and mouse tissue slices.

Formaldehyde (FA) is the simplest active carbonyl species that can be spontaneously produced in the body and plays important roles in human cognitive ability and spatial memory. However, excessive intake of FA may cause a series of diseases, including cancer, diabetes, heart and liver diseases and various neuropathies. Hence, the exploration of sensitive and fast detection methods for FA is crucial to understand and diagnose these diseases. Recently, fluorescent probes have been increasingly employed as powerful tools for detecting a broad range of different small molecules due to their high selectivity, rapid response, convenient operation and relatively non-invasive nature. Thus, we have developed two naphthalimide-based fluorescent probes for detecting FA in cells and in lysosomes. Compared with other FA fluorescent probes, these two probes have several advantages, including high sensitivity and selectivity, excellent two-photon properties and high signal-to-noise ratio. In this protocol, we provide detailed procedures for the synthesis of the two probes; characterization of their sensitivity, selectivity and stability in solution; and representative application procedures for detecting FA in living cells and mouse liver tissue slices. The protocol requires ~88 h to synthesize the probes, ~24 h to characterize the probes in solution and ~25 h to carry out the biological fluorescence imaging experiments in cells and liver tissue slices.

Aurone Derivative Revealing the Metabolism of Lipid Droplets and Monitoring Oxidative Stress in Living Cells.

Lipid droplets (LDs) are closely connected to many physiological processes and abnormal LDs are related to many diseases. Herein, a family of two-photon fluorescence compounds based on the aurone skeleton were developed as efficient LDs imaging probes. They exhibit the obvious solvatochromism effect from blue to orange emission (∼140 nm shift) in various solvents. The robust probes possess low toxicity to living cells, high photobleaching resistance, and superior photostability and can light up LDs with high specificity. Furthermore, the probe DMMB (aurone skeleton with dimethylamino) was carefully applied in real-time monitoring of the morphological changes of LDs and the interactions between LDs and mitochondria under specific physiological conditions (e.g., starvation). We have observed for the first time the dynamic change between mitochondria and LDs when mitochondrial damage is caused by a large excess of H2O2 in a short period of time.

Anxiety Administrated by Dexmedetomidine to Prevent New-Onset of Postoperative Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Graft.

This study aims to evaluate the effect of dexmedetomidine (DEX) sedation for relieving anxiety and the incidence of atrial fibrillation (AF) after off-pump coronary artery bypass graft (OPCABG).This randomized, double-blind, controlled trial was conducted on 196 patients who underwent OPCABG in Shandong Provincial Hospital from July 2017 to June 2018. The patients were randomly assigned to two groups, intervention of DEX group and Propofol (PROP) group. Episodes of postoperative AF (POAF) were identified within 5 days after OPCABG. Perioperative anxiety status was assessed using Zung's Self-Rating Anxiety Scale (SAS). The baseline demographic and surgical characteristics of the population and other outcome variables were evaluated.We analyzed 62 patients in the DEX group and 61 patients in the PROP group. There was no significant difference in SAS anxiety scores between two groups before surgery (P = 0.104), while SAS had significantly after surgery (P = 0.018). The incidence of POAF in the DEX group was lower than that of the PROP group (16.1% versus 32.8%, P = 0.037), and a total of 30 patients (30/123, 24.4%) manifested POAF after OPCABG. Some univariable predictors of POAF were detected. The conceptual model of mediator analyses showed DEX was not only directly related to POAF but was also indirectly related through the independent effect of anxiety level.The findings indicated that patients receiving DEX were more likely to have less incidence of POAF, also uniquely showed DEX administration and POAF processes as a function of anxiety status.