Dimeric Her2-specific affibody mediated cisplatin-loaded nanoparticles for tumor enhanced chemo-radiotherapy.

BACKGROUND: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. RESULTS: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. CONCLUSIONS: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.

[Clinical features of very preterm small-for-gestational-age infants born due to severe preeclampsia].

OBJECTIVE: To study the clinical features of very preterm small-for-gestational-age infants born by cesarean section due to severe preeclampsia. METHODS: Forty-two small-for-gestational-age infants who were admitted from August 2017 to July 2018 and were born due to severe preeclampsia were enrolled as the observation group. Forty very preterm infants who were born to healthy mothers since uterine contractions could not be suppressed were enrolled as the control group. Perinatal features, clinical manifestations of infection, complications, and clinical outcomes were analyzed for the two groups. RESULTS: Within 6 hours and 2-3 days after birth, the observation group had significantly lower white blood cell count (WBC), absolute neutrophil count (ANC), and platelet count (PLT) than the control group (P < 0.05). At 5-7 days after birth, there was no significant difference in WBC between the two groups (P > 0.05), while the observation group still had significantly lower ANC and PLT than the control group (P < 0.05). The observation group had a significantly higher C-reactive protein (CRP) level than the control group at 2-3 days and 5-7 days after birth (P < 0.05). The observation group had a significantly higher proportion of infants with severe infections than the control group (P < 0.05). The observation group had a significantly higher hemoglobin level than the control group within 6 hours after birth (P < 0.05). The observation group had a significantly higher incidence rate of bronchopulmonary dysplasia than the control group (P < 0.05). There was no significant difference between the two groups in the rate of pulmonary hemorrhage, intracranial hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the rate of use of invasive ventilation, and clinical outcomes (P > 0.05). CONCLUSIONS: Very preterm small-for-gestational-age infants born due to severe preeclampsia have a high incidence rate of infection and severe conditions. Early manifestations include reductions in the infection indicators WBC, ANC, and PLT, and CRP does not increase significantly in the early stage and gradually increases at 2-3 days after birth. Most of these infants require invasive ventilation after birth, with bronchopulmonary dysplasia as the main complication. Clinical changes should be closely observed and inflammatory indicators should be monitored for early identification of infection, timely diagnosis, and timely adjustment of antibiotic treatment, so as to improve the outcome.

A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy.

BACKGROUND: It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. RESULTS: In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity. CONCLUSIONS: The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

BACKGROUND: Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. RESULTS: In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. CONCLUSIONS: Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.

Perivascular adipose tissue (PVAT)-derived adiponectin (APN) is a secreted adipokine that protects against hypertension-related cardiovascular injury. However, the regulation of APN expression in hypertension remains to be explored. In this study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Complement 3-deficient hypertensive mice were protected from ANP decrease in the PVAT. APN deficiency blockaded the protective effects of complement inhibition against hypertensive vascular injury. Mechanistically, complement 5a (C5a)-induced TNF-α secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-α up-regulation and APN down-regulation in the PVAT of DOCA mice. Moreover, we detected increased macrophage infiltration and C5a expression associated with decreased APN expression in adipose tissue from patients with aldosterone-producing adenoma. These results identify a novel interaction between macrophages and adipocytes in the PVAT, where complement-mediated inhibition of APN acts as a potential risk factor for hypertensive vascular inflammation.-Ruan, C.-C., Ma, Y., Ge, Q., Li, Y., Zhu, L.-M., Zhang, Y., Kong, L.-R., Wu, Q-H., Li, F., Cheng, L., Zhao, A. Z., Zhu, D.-L., Gao, P.-J. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.

A novel self-assembling peptide with UV-responsive properties.

A novel heptapeptide comprising Ile-Gln-Ser-Pro-His-Phe-Phe (IQSPHFF) identified and found to undergo self-assembly into microparticles in solution. To understand the effects of ultraviolet (UV) irradiation on the self-assembly process, IQSPHFF solutions were exposed to the UV light of 365 nm at room temperature. This exposure was found to have a profound effect on the morphology of the self-assembled aggregates, converting the microparticles to nanorod shapes. Circular dichroism and FTIR studies indicated distinct structural differences in the arrangements of the peptide moieties before and after UV irradiation. However, Mass spectrum analysis and high performance liquid chromatography of the peptide molecules before and after UV irradiation demonstrated that the chemical structure of IQSPHFF was not changed. UV-visible spectroscopy and fluorescence spectroscopy studies showed that the absorption peak both increased after UV irradiation. Overall, our data show that the heptapeptide with UV-responsive properties.

[The role of Treg/Thl7 and calprotectin in ulcerative colitis rat model].

OBJECTIVE: To investigate the roles of helper T cells (Th), regulatory T cells (Treg) and calprotectin in the pathogenesis of ulcerative colitis (UC) in the rat model. METHODS: Thirty rats were randomly divided into normal control (NC) group and UC model (UC) group. The rats of UC group were replicated using the mixed solution of 2, 4,6 trinitrobenzene sulfonic acid (TNBS) / ethanol through the intestinal tract. The rats of NC group were given NaCI solution enema. Three weeks after UC modeling, the morphology changes of colon tissue were observed. The serum levels interleukin (IL)-1ß, IL-10, IL-17, IL-23 and calprotectin (CP) were detected by enzyme-linked immunosorbent assay. The changes of Treg in peripheral blood were measured by flow cytometry. The expressions of IL-17, CP, and transcriptional regulatory proteins of decision Treg cell differentiation and function (FoxP3) in colon tissue were detected by Western blot and immunohistochemistry. RESULTS: UC group was observed with obvious colon tissue injury and inflammatory cells infiltration in intestinal tissue, compared with NC group, the expression of IL-1ß,IL-17,IL-23,CP in serum were increased, while the expression of IL-10, the number of Treg were decreased in UC group (P<0. 05 or P(<0. 01). Compared with NC group, the expression of IL-17, CP in colon tissue were significantly increased in UC group (P(<0.05), and the expression of FoxP3 was increased (P(0. 05). CONCLUSION: Expressions of calprotectin, IL-17 of intestinal tissue, serum are increased in rat of ulcerative colitis, which to lead to the imbalance of Treg/Thl7 cells, and elevate inflammatory responses. These factors have promote the occurrence and development of ulcerative colitis.

Non-invasive left ventricular pressure-strain loop study on cardiac fibrosis in primary aldosteronism: a comparative study with cardiac magnetic resonance imaging.

We investigated the potential diagnostic value of the myocardial work indices based on speckle tracking echocardiography for cardiac fibrosis in patients with primary aldosteronism. Our observational study included 48 patients with primary aldosteronism. We performed conventional echocardiography and the left ventricular pressure-strain loop analysis. We also performed cardiac magnetic resonance imaging to evaluate cardiac replacement fibrosis defined as late gadolinium enhancement (LGE). Patients with LGE (n = 30, 62.5%) had longer duration of hypertension and higher plasma NT-proBNP than those without LGE. Besides, they had a significantly (P ≤ 0.04) higher left ventricular mass index (121.3 ± 19.5 vs. 103.3 ± 20.0 g/m2) and global wasted work (205 ± 78 vs. 141 ± 36 mmHg%) and lower global longitudinal strain (-17.7 ± 1.8 vs. -19.0 ± 2.4%) and work efficiency (GWE, 90.9 ± 2.4 vs. 93.8 ± 1.5%). Receiver Operating Characteristics analysis showed that GWE ≤ 92% had a sensitivity and specificity of 76.7% and 83.3%, respectively, for LGE with the area under curve 0.85 (P < 0.001). In conclusion, both cardiac structure and function were impaired in patients with primary aldosteronism and cardiac fibrosis. The myocardial work index GWE showed significant value for the indication of cardiac fibrosis. Characterization of cardiac fibrosis in primary aldosteronism and the detective value of clinical and echocardiographic indices. Cardiac fibrosis was presented in 30 of the 48 analyzed primary aldosteronism patients with focal high signal intensity in mid-layer myocardium in limited segments as its characterization. The global work efficiency (GWE) had a significantly higher detective value for myocardial replacement fibrosis than other measurements such as left ventricular mass index (LVMI) and NT-proBNP.

A chitosan-camouflaged nanomedicine triggered by hierarchically stimuli to release drug for multimodal imaging-guided chemotherapy of breast cancer.

Breast cancer remains one of the most intractable diseases, especially the malignant form of metastasis, with which the cancer cells are hard to track and eliminate. Herein, the common known carbohydrate polymer chitosan (CS) was innovatively used as a shelter for the potent tumor-killing agent. The designed nanoparticles (NPs) not only enhance the solubility of hydrophobic paclitaxel (PTX), but also provide a "hide" effect for cytotoxic PTX in physiological condition. Moreover, coupled with the photothermal (PTT) properties of MoS2, results in a potent chemo/PTT platform. The MoS2@PTX-CS-K237 NPs have a uniform size (135 ± 17 nm), potent photothermal properties (η = 31.5 %), and environment-responsive (low pH, hypoxia) and near infrared (NIR) laser irradiation-triggered PTX release. Through a series of in vitro and in vivo experiments, the MoS2@PTX-CS-K237 showed high affinity and specificity for breast cancer cells, impressive tumor killing capacity, as well as the effective inhibitory effect of metastasis. Benefit from the unique optical properties of MoS2, this multifunctional nanomedicine also exhibited favorable thermal/PA/CT multimodality imaging effect on tumor-bearing mice. The system developed in this work represents the advanced design concept of hierarchical stimulus responsive drug release, and merits further investigation as a potential nanotheranostic platform for clinical translation.

Clinical features of plastic bronchitis in children after congenital heart surgery.

BACKGROUND: Plastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS. METHODS: We conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021. RESULTS: A total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression. CONCLUSIONS: Children with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.

Cisplatin-loaded mesoporous polydopamine nanoparticles capped with MnO2 and coated with platelet membrane provide synergistic anti-tumor therapy.

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.

[Primary culture and morphological characteristics of human lacrimal adenoid cystic carcinoma cells].

OBJECTIVE: To explore a method of primary culturing human adenoid cystic carcinoma cells of lacrimal gland. METHODS: Experiment research. Tumor tissue was obtained from the surgical material of a patient diagnosed as lacrimal adenoid cystic carcinoma in Tianjin Medical University Eye Hospital during May 16th to June 1st.We gained primary cells via tissue culture techniques. Mixed cells were removed through several ways.Observed cell morphological characteristics by phase contrast microscope, scanning electron microscope and transmission electron microscope. Cyto-immunochemical staining was applied to detect the expressions of vimentin, desmin, S-100, cytokeratin, pan and CD34. Their expressions were also detected in the tumor tissue except CD34. Made cell growth curve and calculated cell doubling time. RESULTS: The outgrowth of cells was observed by day 5 after seeding tissues, and then cells generated slowly. The first passage proceeded by day 32, and the classical epithelioid cell colonies was observed by day 69 after inoculation. Purified cells of human lacrimal adenoid cystic carcinoma were obtained after the removal of mixed cells through several ways, which have been successfully subcultured for more than 100 passages. The 25th passage LACC cells appeared to be typically epithelioid cells, they showed contact inhibition as the density high enough.SEM and TEM showed the 25th passage LACC cells were malignant tumor cells poorly differentiated. They showed positive reaction with vimentin, cytokeratin (pan) as well as S-100, but negative reaction with desmin and CD34, which were consistent with the tumor tissue. The cell growth curve turned like a sigmoid one, and the cell doubling time was 37.1 h. CONCLUSIONS: We gained purified LACC cells, and understood the morphological characteristics, laying the foundation for the establishment of a human lacrimal adenoid cystic carcinoma cell line.

[The expression of MMP-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland].

OBJECTIVE: To investigate the expression of matrix metal proteinase (MMP)-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland as well as their relation with biological behaviour of adenoid cystic carcinoma. METHODS: Experimental study. The research objects were 60 cases of adenoid cystic carcinoma of lacrimal gland which were collected from No.2 Hospital of Tianjin Medical University from January 1991 to Jule 2011. There were 25 males and 35 females aged from 29 to 42 years. Based on histological revision, there were 36 cases of cribriform-tubular subtype and 24 cases of solid subtype. Forty-five cases were primary lesions and 15 cases were recurrent lesions. Ten samples of normal lacrimal gland around polymorphic adenoma were selected as the control group. The expression of CD105, MMP-2 and MMP-9 were evaluated by immunohistochemistry. The microvessel density (MVD) was defined by expression of CD105. One way ANOVA, χ(2)-test and spearman correlation test were used to analyzed the data. RESULTS: The number of MVD [(17.71 ± 5.63)/100 folds field of vision] and the positive rates of MMP-2 (45.0%, 27/60) and MMP-9 (55.0%, 33/60) in the samples of adenoid cystic carcinoma of lacrimal gland were higher than those in the normal lacrimal gland [the number of MVD was (0.70 ± 0.95)/100 folds field of vision, the expressions of MMP-2 and MMP-9 were negative] (t' = 2.039, P < 0.05; χ(2) = 5.550, P < 0.05; χ(2) = 8.315, P < 0.01), the solid subtypes had more MVD [(26.12 ± 5.32)/100 folds field of vision] and higher positive rates of MMP-2 (62.5%, 15/24) and MMP-9 (79.2%, 19/24) than the cribriform-tubular subtypes (t' = 2.060, P < 0.05; χ(2) = 4.950, P < 0.05; χ(2) = 9.439, P < 0.05); the recurrent lesions had more MVD and higher positive rate of MMP-2 and MMP-9 than the primary lesions (t' = 2.129, P < 0.05; χ(2) = 9.899, P < 0.05; χ(2) = 8.103, P < 0.05). The number of MVD in ACC of lacrimal gland patients was correlated with the positive rate of MMP-2 and MMP-9 respectively (rs = 0.636, P < 0.05; rs = 0.524, P < 0.05). CONCLUSIONS: The number of MVD and the expression of MMP-2 and MMP-9 are higher level in adenoid cystic carcinoma of lacrimal gland and are significantly correlated with pathological type and recurrence. Detecting the number of MVD and the expression of MMP-2 and MMP-9 may become biological indexes for malignancy, recurrence and metastasis of adenoid cystic carcinoma of lacrimal gland.

Polydopamine-cloaked Fe-based metal organic frameworks enable synergistic multidimensional treatment of osteosarcoma.

One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy, and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d-arginine (d-Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O2 to hydrogen peroxide and gluconic acid, blocking the cells' energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe3+, which reacts with H2O2 to produce reactive oxygen species and thus stimulates the conversion of d-Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe3+ to enhance the T1-weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.

A multifunctional nanocomposite coated with a BSA membrane for cascaded nitric oxide therapy.

Gas therapy based on nitric oxide (NO) has emerged as a potential therapeutic approach for cancer, and in conjunction with multi-mode combination therapy, offers new possibilities for achieving significant hyperadditive effects. In this study, an integrated AI-MPDA@BSA nanocomposite for diagnosis and treatment was constructed for PDA based photoacoustic imaging (PAI) and cascade NO release. Natural NO donor L-arginine (L-Arg) and photosensitizer (PS) IR780 were loaded into mesoporous polydopamine (MPDA). Bovine serum albumin (BSA) was conjugated to the MPDA to increase the dispersibility and biocompatibility of the nanoparticles, as well as to serve as a gatekeeper controlling IR780 release from the MPDA pores. The AI-MPDA@BSA produced singlet oxygen (1O2) and converted it into NO through a chain reaction based on L-Arg, enabling a combination of photodynamic therapy and gas therapy. Moreover, due to the photothermal properties of MPDA, the AI-MPDA@BSA performed good photothermal conversion, which allowed photoacoustic imaging. As expected, both in vitro and in vivo studies have confirmed that the AI-MPDA@BSA nanoplatform has a significant inhibitory effect on cancer cells and tumors, and no apparent systemic toxicity or side effects were detected during the treatment period.

Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells.

AIM: To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation (LACC-HGT) primary cells cultured by high-grade transformation tissue and non-high-grade transformation (non-HGT) primary cells cultured by non-high-grade transformation tissue in proliferation, metastasis, drug susceptibility, and genes. METHODS: LACC-HGT primary cells were established by tissue block culture, and the 4th to 10th generation primary cells were selected as research objects. The cells were preliminarily identified by immunofluorescent staining. The differences between non-HGT and LACC-HGT primary cells in terms of proliferation, metastasis, and drug susceptibility were compared by cell counting kit-8 (CCK-8) assay, wound healing, and drug sensitivity experiments. Differentially expressed genes were screened using mRNA array. Gene expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: LACC-HGT primary cells were successfully cultured by tissue block culture. Immunofluorescence staining results showed that cytokeratin (CK) and CK7 expression levels were positive in LACC-HGT primary cells. CCK-8 results showed that the proliferation ability of LACC-HGT cells was significantly higher than that of non-HGT cells. Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells. LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells. Compared with non-HGT cells, 9566 differentially expressed genes were found in LACC-HGT primary cells, of which 5162 were up-regulated and 4404 were down-regulated. The expression of N-acetylneuraminate pyruvate lyase (NPL), MARVEL domain containing 3 (MARVELD3), syntabulin (SYBU), and allograft inflammatory factor 1 (AIF1) was higher in LACC-HGT cells than in non-HGT cells, whereas that of periostin (POSTN) was lower. CONCLUSION: LACC-HGT primary cells have faster proliferation, stronger migration ability, and poorer sensitivity to chemotherapy drugs than non-HGT primary cells. The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different. These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts.

Development of an automatic approaching system for electrochemical nanofabrication using visual and force-displacement sensing.

In this paper, a fast automatic precision approaching system is developed for electrochemical nanofabrication using visual and force-displacement sensing. Before the substrate is fabricated, the template should approach the substrate accurately to establish the initial gap between the template and substrate. During the approaching process, the template is first quickly moved towards the substrate by the stepping motor until a specified gap is detected by the visual feedback. Then, the successive approach using the switch of macro-micro motion with a force-displacement sensing module is triggered to make the template contact with the substrate to nanometre accuracy. The contact force is measured by the force-displacement sensing module which employs the high-resolution capacitive displacement sensor and flexure compliant mechanism. The high sensitivity of this capacitive displacement sensor ensures high accuracy of the template-substrate contact. The experimental results show that the template can reach the substrate accurately and smoothly, which verifies the effectiveness of the proposed approaching system with the visual and the force-displacement sensing modules.

[Surgical repair of truncus arteriosus in children: early results and long-term outcomes].

OBJECTIVE: To recite early results and long-term outcomes after surgical repair of persistent truncus arteriosus (PTA). METHODS: The clinic data of 54 patients underwent surgical repair for PTA from January 1999 to December 2009 was analyzed retrospectively. There were 36 male and 18 female patients, with a mean age of (9 ± 10) months (range, 1 to 38 months; median, 5 months). Preoperative mechanical ventilation was required in 5 patients. The surgical procedures were closure of ventricular septal defect and re-establishment of continuity between right ventricle and pulmonary artery. The right ventricular outflow tract (RVOT) was reconstructed by direct anastomosis pulmonary artery to right ventriculotomy with anterior wall patch enlargement (28 cases), or by inserting conduits (26 cases). Valvuloplasty were performed in 4 patients with truncal valves moderate to severe insufficiency and aortoplasty in 3 patients with interrupted aortic arch (IAA). RESULTS: There were 3 patients (5.6%) died of pulmonary hypertensive crisis in hospital. The mean duration of ventilation was 6.8 days in 5 patients who were intubated before operation, while the others were 3.6 days. Forty-seven (92.2%) patients were followed-up for mean (6.8 ± 2.5) years (from 2.5 to 11.0 years). There were 2 patients with mild to moderate aortic regurgitation. One patient with aortic arch obstruction underwent balloon dilatation 2 years postoperatively. Among those patients who underwent direct anastomoses, 8 (32.0%) patients had pulmonary branch stenosis at 7 months to 1.5 years postoperatively, 12 (48.0%) patients were freedom from surgical reintervention 5.0 to 11.0 years postoperatively. Among those inserting conduits, 7 patients (31.8%) had conduit stenosis at 2.8 to 7.0 years after operation. Reoperations were performed for RVOT in 15 patients and there was no mortality. CONCLUSIONS: It is difficult to treat the PTA patients with IAA, intra-mural coronary artery or mechanical ventilation support before operation. The technique of direct anastomosis between pulmonary artery and right ventricle offers the potential growth for RVOT, but bilateral pulmonary branch stenosis may be occurred at earlier period of postoperation in some patients.

Data-driven fractional order feedback and model-less feedforward control of a XY reluctance-actuated micropositioning stage.

This paper proposes a compound data-driven control method to solve the problems of low damping resonance, different dynamic properties, and hysteresis in the large-range compliant micropositioning stage driven by a Maxwell reluctance actuator. First, in order to verify the proposed control algorithm, a reluctance-actuated, XY compliant micropositioning stage is constructed according to the principle of operation of a reluctance actuator. Second, in order to eliminate the influence of complex dynamics on the controller design, a fractional order proportional-integral feedback controller is designed using a data iterative feedback turning algorithm. Third, the finite impulse response feedforward filter is optimized using experimental data, and the on-line inverse estimation of the system frequency response function and its iterative feedforward compensation are carried out to further eliminate the influence of light damping resonance. Finally, the proposed control method is used for tracking the experiment and compared with other methods. The experimental results show that the proposed control method can better meet the requirements of high precision, fast speed, and strong anti-interference ability for large stroke micro/nanopositioning and tracking.