Metallic Copper-Based Dual-Enzyme Biomimetic Nanoplatform for Mild Photothermal Enhancement of Anticancer Catalytic Activity.

Background: Chemodynamic therapy (CDT) is recognized as a promising cancer treatment. Recently, copper sulfide nanostructures have been extensively employed as Fenton-like reagents that catalyze the formation of acutely toxic hydroxyl radicals (·OH) from hydrogen peroxide (H2O2). However, CDT therapeutic potency is restricted by the tumor microenvironment (TME), such as insufficient amounts of hydrogen peroxide, excessive glutathione levels, etc. To address these disadvantages, glucose oxidase (GOx) or catalase (CAT) can be utilized to enhance CDT, while low therapeutic efficacy still inhibits their future applications. Our previous study revealed that mild photothermal effect could boost the CDT catalytic effectiveness as well as GOx enzyme activity over a range. Results: We engineered and constructed a hollow CuS nanoplatform loaded with GOx and CAT, coating with macrophage membranes (M@GOx-CAT@CuS NPs). The nanoplatforms allowed enhancement of the reactive oxygen species creation rate and GOx catalytic activeness of CDT through mild phototherapy directed by photoacoustic imaging. After actively targeting vascular cell adhesion molecule-1 (VCAM-1) in cancer cells mediated by macrophage membrane coating, M@GOx-CAT@CuS NPs released GOx and CAT under near-infrared irradiation. GOx catalyzed the formation of H2O2 and gluconic acid with glucose, creating a better catalytic environment for CDT. Meanwhile, CAT-catalyzed H2O2 decomposition to generate sufficient oxygen, appropriately alleviating the oxygen shortage in the TME. In addition, starvation effects decreased adenosine triphosphate levels and further underregulated heat shock protein expression to reduce the heat resistance of tumor cells, resulting in a better mild phototherapy outcome. Both in vitro and in vivo experiments demonstrated that the newly developed M@GOx-CAT@CuS nanoplatform has remarkable synergistic anticancer therapeutic effects. Conclusion: The cascade reaction-enhanced biomimetic nanoplatform opens up a new avenue for precision tumor diagnostic and therapeutic research.

Laser-activated nanoparticles for ultrasound/photoacoustic imaging-guided prostate cancer treatment.

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo. In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects.

Sonosensitive Phase-Changeable Nanoparticle Mediated Enhanced Chemotherapy in Prostate Cancer by Low-Intensity Focused Ultrasound.

Prostate cancer (PCa) is one of the most common cancer types. Early detection of PC offers the best chance of successful treatment. A noninvasive, image-guided therapy mediated by targeted nanoparticles (NPs) has the potential to improve the efficacy and safety of cancer therapies. Herein, we report a sonosensitive nanoparticle modified with anti-PSMA (prostate-specific membrane antigen) antibodies to activate target prostate tumors. These nanoparticles (PFP@IR780@PTX@liposome NPs) were co-loaded with the chemotherapeutic agent docetaxel and the sonosensitizer IR780, as well as phase-changeable perfluorocarbon (PFC) liquids. The liquid-gas phase change could be induced by low-intensity focused ultrasound (LIFU) in vitro. We found that the PFP@IR780@PTX@liposome NPs can specifically accumulate in prostate tumors after LIFU irradiation, as monitored by ultrasound and photoacoustic imaging. Meanwhile, docetaxel was controllably released from the nanoparticles to achieve enhanced chemotherapeutic therapy in vivo. These sonosensitive phase-changeable NPs can visually treat prostate cancers effectively and have a clinical potential.

Clinical efficacy of turtle shell decocted pills for endometriosis and their influence on cellular immunity.

OBJECTIVE: To explore the therapeutic efficacy of the levonorgestrel-releasing intrauterine system combined with turtle shell decocted pills for endometriosis and their effect on cellular immune function. METHODS: Clinical data of 118 patients with endometriosis admitted to Taizhou First People's Hospital from January 2019 to January 2020 were retrospectively analyzed. The patients were assigned into a single-drug group (n=68) and a combined traditional Chinese medicine group (n=50) according to treatment methods. The single-drug group was treated with the levonorgestrel-releasing intrauterine system, and the combined traditional Chinese medicine group was treated with additional turtle shell decocted pills for three cycles for a total of 12 weeks. Enzyme-linked immunosorbent assay was adopted to measure the concentration of Th1 cytokines (tumor necrosis factor (TNF)-α and interferon (IFN)-γ) and Th2 cytokines (interleukin (IL)-6 and IL-10), and the protein level of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1). The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) were compared between the two groups. The response rate of treatment, the control rate of blood pressure and the incidence of adverse reactions were recorded in both groups. RESULTS: The response rate of treatment in the combined traditional Chinese medicine group was higher than that in the single-drug group (P<0.05). Compared to before treatment, the TNF-α and IFN-γ increased in both groups after treatment, and the expressions were higher in the combined traditional Chinese medicine group than in the single-drug group (all P<0.05). After treatment, the levels of IL-6, IL-10, PD-1, and PD-L1 decreased, and the decreases in the combined traditional Chinese medicine group were greater than those in the single-drug group (all P<0.05). Serum LH, FSH and E2 levels before and after the treatment in the two groups were not statistically different (all P>0.05). The incidence of treatment-related adverse reactions between the two groups of patients was also not statistically different (P>0.05). CONCLUSION: Turtle shell decocted pills can increase the clinical efficacy of levonorgestrel-releasing intrauterine system in the treatment of endometriosis, reduce levels of PD-1, and PD-L1 and improve cellular immune function. The pills do not affect the secretion of ovarian hormones or increase adverse reactions.

Over-immunity mediated abnormal deposition of lignin arrests the normal enlargement of the root tubers of Rehmannia glutinosa under consecutive monoculture stress.

The rapid accumulation of lignin in the cell wall is one of important immune defense mechanism in response to adversity stress in plants. In this study, we found that the enlargement of the root tubers of Rehmannia glutinosa (R. glutinosa) is arrested under consecutive monoculture stress, and this process is accompanied by abnormal accumulation of lignin. Meanwhile, the function of key catalytic enzyme genes in lignin biosynthetic pathway under consecutive monoculture stress was systematically analyzed, of which roles of core genes were validated using reverse genetics. We elucidated that an abnormal deposition of lignin in R. glutinosa roots, induced by consecutive monoculture stress, and arrested the enlargement of root tubers. Additionally, by manipulating the key catalytic enzyme gene RgCCR6, we were able to alter lignin content of roots of R. glutinosa, thereby affecting tuber enlargement. We speculate that cell lignification is an important defense strategy in resistance against consecutive monoculture stress, but the overreacted defense hindered the normal enlargement of root tubers. The findings provide new insights for effectively improving yield reductions of root crops subjected to environmental stress.

Integrated Analysis of Transcriptomic and Proteomics Data Reveals the Induction Effects of Rotenoid Biosynthesis of Mirabilis himalaica Caused by UV-B Radiation.

Mirabilis himalaica (Edgew.) Heimerl is one of the most important genuine medicinal plants in Tibet, in which the special plateau habitat has been associated with its excellent medicinal quality and efficacy. However, the mechanisms by which environmental factors affect biosynthesis of secondary metabolic components remain unclear in this species. In this study, RNA sequencing and iTRAQ (isobaric Tags for Relative and Absolute Quantification) techniques were used to investigate the critical molecular "events" of rotenoid biosynthesis responding to UV-B radiation, a typical plateau ecological factor presented in native environment-grown M. himalaica plants. A total of 3641 differentially expressed genes (DEGs) and 106 differentially expressed proteins (DEPs) were identified in M. himalaica between UV-B treatment and control check (CK). Comprehensive analysis of protein and transcript data sets resulted in 14 and 7 DEGs from the plant hormone signal transduction and phosphatidylinositol signaling system pathways, respectively, being significantly enriched. The result showed that the plant hormone signal transduction and phosphatidylinositol signaling system might be the key metabolic strategy of UV-B radiation to improve the biosynthesis of rotenoid in M. himalaica. At same time, most of the DEGs were associated with auxin and calcium signaling, inferring that they might drive the downstream transmission of these signal transduction pathways. Regarding those pathways, two chalcone synthase enzymes, which play key roles in the biosynthesis of rotenoid that were thought as the representative medicinal component of M. himalaica, were significantly upregulated in UV-B radiation. This study provides a theoretical basis for further exploration of the adaptation mechanism of M. himalaica to UV-B radiation, and references for cultivation standardization.

Determination of dihydralazine based on chemiluminescence resonance energy transfer of hollow carbon nanodots.

The famous weak chemiluminescence (CL) system of potassium permanganate and sodium bisulfite (KMnO4-HSO3-) was enhanced by the hollow fluorescent carbon nanodots (HCNs). The investigation of mechanism revealed that the enhanced CL was induced by the excited-state HCNs (HCNs⁎), which could be produced from the electron-transfer annihilation of positively charged HCNs (HCNs+) and negatively charged HCNs (HCNs-) as well as by CL resonance energy transfer (CRET) from excited SO2 (SO2⁎)/1O2 to HCNs. The dihydralazine sulfate (DHZS) had a diminishing effect on the CL of HCNs-KMnO4-HSO3- system due to the competitive consumption of O2-. Under the optimal conditions, the reduced CL signal with the concentration of DHZS was linear in the range of 1.0×10-7-7.0×10-5mol/L with a detection limit of 3.0×10-8mol/L. The relative standard deviation for seven repeated determination of 5.0×10-6mol/L DHZS was 2.1%. The established method was applied to the determination of DHZS in pharmaceutical preparations, human urine and plasma samples with good precision and accuracy.

Covalently Connected Polymer-Protein Nanostructures Fabricated by a Reactive Self-Assembly Approach.

The synthesis of polymer-protein nanostructures opens up a new avenue for the development of new biomaterials. In this research, covalently connected polymer-protein nanostructures were fabricated through a reactive self-assembly approach. Poly(tert-butyl methacrylate-co-pyridyl disulfide methacrylamide) (PtBMA-co-PPDSMA) was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. Covalently connected nanostructures (CCNs) with hydrophobic polymer cores and hydrophilic protein coronae were prepared by adding solutions of PtBMA-co-PPDSMA/DMF to aqueous solutions of bovine serum albumin (BSA). The thiol-disulfide exchange reaction between pyridyl disulfide groups on the polymer chains and thiol groups on the protein molecules plays a key role in the fabrication of CCNs. The self-assembly process was investigated by dynamic light scattering (DLS) and stopped-flow techniques. DLS results indicated that the sizes of the CCNs were determined by the initial polymer concentration, the BSA concentration, and the average number of thiol groups on BSA molecules. TEM and sodium dodecyl sulfate polyacrylamide gel electrophoresis were used to analyze the nanostructures. Far-UV circular dichroism results demonstrated that the original folded conformations of BSA molecules were basically maintained in the reactive self-assembly process. Compared with native BSA, the secondary structure and conformation change of coronal BSA induced by urea or thermal treatment were remarkably suppressed. The cytotoxicity assays demonstrated that the CCNs were essentially nontoxic to Hela and COS-7 cells.

Protein-Cross-Linked Triple-Responsive Polymer Networks Based on Molecular Recognition.

Hydrogels containing protein components are a type of promising biomaterial. In this paper, we designed triple-responsive polymer-protein networks based on molecular recognition. Reduced bovine serum albumin (BSA) was modified with multiple ß-cyclodextrin (ßCD) by thiol-disulfide exchange reaction. The ßCD-modified BSA was added into the aqueous solution of acrylamide copolymer with pendant adamantyl groups, resulting in the formation of polymer-protein network structures. The assembled polymer networks show triple-responsive behaviors upon treatment with trypsin, reduced glutathione, or native ßCD. The network structures may find applications in tissue engineering and drug controlled release.

[Sinonasal teratocarcinosarcoma: a clinical, radiologic and pathologic study of 5 cases].

OBJECTIVE: To study the clinical, radiologic and pathologic features, as well as differential diagnosis of teratocarcinosarcoma in nasal cavity and paranasal sinuses. METHODS: Light microscopic examination and immunohistochemical study was performed in 5 cases of sinonasal teratocarcinosarcoma. The clinical, radiologic and pathologic features were analyzed and the literature was reviewed. RESULTS: All 5 patients were males and their age ranged from 34 to 43 years (mean age = 39 years). The clinical presentation was nasal obstruction, epistaxis and headache. Physical examination often revealed a polypoid mass with contact bleeding. Computed tomography showed a homogeneous nasal mass with obturation of sinuses. Cystic changes, calcification or ossification was not observed. Histologically, the tumor showed a heterogeneous admixture of components from the 3 germ cell layers, exhibiting various degrees of maturation. Squamous epithelium, smooth muscle cells, chondro-osseous tissue, intestinal or respiratory type epithelium, "fetal-type" clear cells and immature neuroepithelium were commonly seen. Immunohistochemical study demonstrated that the epithelial component expressed cytokeratin and epithelial membrane antigen, while the mesenchymal component variably expressed vimentin, smooth muscle actin and S-100 protein. On the other hand, the neuroepithelial component expressed neuron-specific enolase, synaptophysin and chromogranin, and the primitive component expressed CD99. The initial biopsy diagnosis included capillary hemangioma, olfactory neuroblastoma, craniopharyngioma and malignant mixed tumor. Follow-up information was available in all patients. Two of which had local recurrence and 1 had cervical lymph node metastasis. CONCLUSIONS: Sinonasal teratocarcinosarcoma is a rare and highly malignant tumor occurring in sinonasal tract. It manifests mainly in adult males and is characterized by a complex admixture of teratomatous and carcinosarcomatous components. "Fetal-type" clear cells, squamous epithelium and immature neuroepithelium represent important histologic characteristics useful in diagnosis.

[Experiences in maintenance and repair cost control of medical equipments].

This paper introduces methods to control the cost of maintenance and repair for medical equipments through service team training, service contract control, system establishment and outside service resources, etc..

[A discussion about the network safety of the hospital information system].

This paper introduces the measures guaranteeing the network safety of the hospital information system.

[Malignant fibrous histiocytomas of larynx].

OBJECTIVE: To explore the histopathology, diagnosis and treatment of malignant fibrous histiocytomas (MFH) of larynx. METHODS: The clinical and pathologic features of 9 cases with MFH of larynx were reviewed retrospectively. RESULTS: All the 9 cases with MFH of larynx were adults (the age ranged from 43 to 87 years; average 56 years); 8 were men and 1 woman. The tumor of eight cases originated in glottic area and 1 case occurred in supraglottic area. The histological diagnosis was difficult, so the immunohistochemical studies in 5 cases were examined. Because surgical resection was a mainly treatment, seven patients underwent total laryngectomy and 2 cases underwent frontal partial laryngectomy. Six patients were followed up for more than 3 years and no patient died of MFH after surgical resection. CONCLUSION: The diagnosis of MFH of larynx was sometimes difficult and immunohistochemistry could be helpful. The mainly treatment of MFH of larynx was surgical resection by total laryngectomy or partial laryngectomy.