Case Report: Pulmonary sarcomatoid carcinoma complicating TP53 mutation treated successfully with Tislelizumab combined with Anlotinib-a case report.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen "albumin paclitaxel + cisplatin," but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 105 IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

Which Has a Greater Impact on the Recurrence in Young Breast Cancer Patients: Recent Childbirth or Recent Breastfeeding?

Purpose: This study explored the effects of recent childbirth and recent breastfeeding on the risk of recurrence in patients with postpartum breast cancer (PPBC). Materials and Methods: A bidirectional cohort study was conducted in the First Affiliated Hospital of Nanjing Medical University. 1013 young female breast cancer patients between May 2003 and October 2019 were enrolled. Breast cancer cases were grouped according to the time between giving birth or weaning and diagnosis. The end point of the analysis was disease-free survival (DFS). Results: Breast cancer patients diagnosed within 2 years after parturition showed more tumor characteristics that represented poor prognosis and remained at an increased risk for recurrence, even after adjusting for confounding factors (HR = 1.83, p=0.035). When the analysis was limited to patients with ER positive or histological grades I and II, they had a higher risk of recurrence. When weaning was used as the grouping node, patients diagnosed within 2 years after weaning did not show a higher risk of recurrence after adjustment, even when analysis was nearly limited to ER-positive patients. Conclusion: Recent reproductive history is an independent prognostic factor and seems to have a stronger impact on breast cancer with lower malignancy. In addition, the effect of recent childbirth on the recurrence of young breast cancer is significantly stronger than that of recent breastfeeding.

Association Between White Matter Hyperintensities and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objectives: Previous studies of the associations between white matter hyperintensities (WMH) and chronic kidney disease (CKD) were still conflicting; therefore, our study aimed to conduct a systematic review of all of the available research on this topic and a meta-analysis of the association between WMH and CKD among observational studies. Setting and Design: Systematic review and meta-analysis. Outcome Measures: Severity of WMH. Methods and Participants: All relevant studies in public databases were examined until 15 November 2020. Two independent reviewers assessed all the included studies using the Cross-Sectional/Prevalence Study Quality (CSSQ) scale, and then literature review and meta-analyses were undertaken. Results: We pooled the odds ratio (OR) for the presence of WMH, periventricular hyperintensities (PVH), and deep subcortical white matter hyperintensities (DWMH) of patients with CKD vs. non-CKD patients by subgroup analysis, and the results obtained were WMH OR 2.07, 95% CI [1.58, 2.70], PVH OR 2.41, 95% CI [1.90, 3.05], and DWMH OR 2.11, 95% CI [1.60, 2.80], respectively. The main outcome showed that patients with CKD were more likely to have WMH in the brain compared to the normal controls. Another meta-analysis showed a statistically significant decline in renal function in patients with moderate to severe WMH compared with those with no to mild WMH. Conclusions: The findings indicated that patients with CKD were more likely to experience WMH than demographically matched controls. On the other hand, patients with moderate to severe WMH in the brain had poor renal function more frequently than those with no to mild WMH.

MicroRNA-208a-3p participates in coronary heart disease by regulating the growth of hVSMCs by targeting BTG1.

Human vascular smooth muscle cells (hVSMCs) are crucial in the progression of coronary heart disease (CHD). The present study aimed to investigate the role of microRNA-208a-3p (miR-208a-3p) in hVSMCs. Reverse transcription quantitative-PCR was performed to detect the levels of miR-208a-3p in the peripheral blood samples of patients with CHD and healthy volunteers. The results showed that miR-208a-3p was significantly upregulated in peripheral blood samples from patients with CHD compared with in healthy volunteers. Bioinformatics analysis and dual-luciferase reporter assays indicated that B-cell translocation gene 1 (BTG1) was a direct target gene of miR-208a-3p, and was downregulated in the peripheral blood samples of patients with CHD. Furthermore, this study also suggested that miR-208a-3p served an inhibitory role in the proliferation of hVSMCs, induced cell apoptosis, promoted the protein expression of Bax and reduced Bcl-2 protein expression; however, these effects were reversed by BTG1 silencing. In addition, the role of the PI3K/AKT pathway in mediating hVSMC apoptosis was examined via western blot analysis. Results indicated that inhibition of miR-208a-3p decreased phosphorylated (p)-AKT protein expression levels and the ratio of p-AKT/AKT in hVSMCs; however, BTG1-small interfering RNA abolished these effects. Taken together, these findings revealed that miR-208a-3p served a critical role in CHD development, regulating hVSMC function via targeting of BTG1, which was associated with the PI3K/AKT signaling pathway. Therefore, downregulated miR-208a-3p may serve as an ideal therapeutic target for CHD diagnosis and therapy.

Long Noncoding RNA LINC01116 Contributes to Gefitinib Resistance in Non-small Cell Lung Cancer through Regulating IFI44.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, have been established as first-line treatments for non-small cell lung cancer (NSCLC) patients and have exhibited notable clinical efficacy. However, resistance to TKIs has become one of the major obstacles in improving the therapeutic efficacy of patients with NSCLC. This study aims to investigate the role of the long non-coding RNA (lncRNA) LINC01116 in gefitinib resistance of NSCLC and explore its underlying mechanism. In this study, we found that LINC01116 is upregulated in the gefitinib-resistant NSCLC cells and tissues. Loss- and gain-of-function assays uncovered that LINC01116 downregulation sensitized gefitinib resistance, whereas the overexpression of LINC01116 conferred PC9/R cells to gefitinib resistance. Moreover, LINC01116 silencing increased IFI44 expression. Overexpression of IFI44 reversed the resistance to gefitinib in PC9/R cells, and rescue experiments confirmed that LINC01116 affects the gefitinib resistance of PC9/R cells partly dependent on regulating IFI44 expression. Moreover, downregulation of LINC01116 increased the sensitivity of PC9/R cells to gefitinib in vivo. Our study demonstrates that LINC01116 plays a critical role in gefitinib resistance of NSCLC cells by affecting IFI44 expression, providing a novel therapeutic target to overcome TKI resistance in NSCLC.

High-Performance Worm-like Mn-Zn Ferrite Theranostic Nanoagents and the Application on Tumor Theranostics.

Previous reports from our team revealed the significant potential advantage of Mn-Zn ferrite nanoparticles (NPs) in magnetic resonance imaging (MRI), whereas anisotropic NPs reportedly increased the blood circulation time of nanocarriers. Thus, anisotropic Mn-Zn ferrite displayed a huge potential in cancer synchronous diagnosis and treatment, that is, enhanced MRI observation was performed simultaneously when drug-targeted delivery therapy was applied to the tumor. Here, we developed three shaped Mn-Zn ferrite (Mn0.63Zn0.37Fe2O4) MNPs used as cancer theranostic nanoagents and compared the effect of the three shaped MNPs on cancer theranostics. Compared to the monodisperse sphere MNPs (S-MNPs-PPR) and clustering MNPs (C-MNPs-PPR), worm-like Mn-Zn ferrite MNPs (W-MNPs-PPR) achieved better results in T2-weighted MRI and achieved more sustained drug release than S-MNPs-PPR and more complete drug release than C-MNPs-PPR in vitro. Additionally, polyethylene glycol (PEG) coating and RGD modification encouraged the three shaped MNPs to evade the recruitment of macrophages more easily and to target the integrin-enriched endothelial cells instead. Meanwhile, W-MNPs-PPR coupled with Paclitaxel (PTX) exhibited more delivery of PTX in the integrin-enriched cells than the other two shaped MNPs, and the content of PTX was far more than that of the wild-type Taxol control group. What is more, in vivo results demonstrated that PTX-coated W-MNPs-PPR not only gained good dual-mode imaging in the tumor (MRI and fluorescence images) but also achieved longer blood circulation time and more PTX-targeted delivery to the tumor, as well as more efficiency in tumor cell killing, which make the simultaneous diagnosis and treatment of tumors to be conducted. Therefore, our works further revealed the importance of the NP shape on its functionality and ultimately provided an alternative and efficient worm-like theranostic nanoagent for tumor theranostics.

A label-free aptasensor for the detection of tetracycline based on the luminescence of SYBR Green I.

A novel fluorescent method based on tetracycline-binding aptamers and the luminescence of SYBR Green I (SGI) was established for the sensitive and selective detection of tetracycline. Under natural conditions, the aptamers of tetracycline show the G-quadruplex spatial structures while SGI is nearly nonfluorescent in aqueous solution. After mixture with the G-quadruplex structured aptamers, SGI can recognize and intercalate into the aptamers, resulting in a strong fluorescence emission. When the target tetracycline was added into the solution, the specific recognition and high-affinity binding of aptamers with tetracycline will induce the conformational changes of aptamers from G-quadruplex structures to hairpin structures. Thereafter, SGI will be released from the aptamer molecules, leading to the fluorescence decline. The quantitative detection of tetracycline can be achieved by measuring the fluorescence change of the system. Under the optimum conditions, the linear range of tetracycline in the milk was from 5 to 25 µg/mL, and the detection limit was as low as 0.10 µg/mL. The recoveries of the spiked milk samples were in the range of 98.98%-104.67% with the relative standard deviations (RSDs) of 0.16%-0.67%, and the results were in agreement with those from HPLC. Therefore, the biosensor based on the specific recognition of aptamers and the fluorescence properties of SGI can detect the tetracycline in milk accurately, rapidly and specifically.

[History evolution of salt production and processing with brine].

Salt is an important excipient for Chinese medicine salt. The standardization of its quality is conducive to ensuring the quality of Chinese medicine pieces. In this paper, the processing with brine and the processing auxiliary salt were studied from three aspects： the history evolution of salt, the history evolution of processing with brine, and the modern research of processing with brine. It has been found that salt plays an important role in the history of China. It has a long history and a wide variety. The salt used in the processing of traditional Chinese medicine mainly includes three categories： common salt, halitum and white salt. The quality of salt is closely related to its origin and processing, mainly based on the color and the place of origin. In ancient times, the varieties of salt used in the production of different Chinese herbal medicines were different, which might be related to the nature of drugs. The primary purpose of processing with brine is to increase the efficacy of drugs. At present, there are many reports on optimizing the preparation technology of processing with brine, but the evaluation indexes are quite different, and its scientific nature is to be discussed. The processing method with brine and its processing auxiliary materials are lacking of relevant evaluation standards and quality standards, which is not conducive to the healthy development of Chinese herbal pieces. In this paper, the relevant literature was studied in order to provide reference for the establishment of standards for salt processing excipient in traditional Chinese medicine.

Paclitaxel-Loaded Magnetic Nanoparticles: Synthesis, Characterization, and Application in Targeting.

Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid therapy in critical patients in clinic integrated system. Herein, we synthesized paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)-lysine-oleic acid2 (PTX-MNPs-PLO), which is expected to act as a magnetic resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs were synthesized by thermal decomposition. Dialysis method was applied to prepare PTX-MNPs-PLO with 3 different PEG molecular weights (1000, 2000, and 4000 Da), which were subsequently freeze-dried into powders. PTX-MNPs-PLO was characterized by transmission electron microscope, scanning electron microscope, thermogravimetric analysis, vibrating sample magnetometer, and MRI. What is more is that pharmacokinetics and distribution in vivo were processed, the results of which exhibited that PTX-MNPs-PLO2000 had the longer circulation lifetime compared with Taxol, PTX-MNPs-PLO1000, and PTX-MNPs-PLO4000. Results of magnetic targeting in kidneys suggested that deep buried or ultrasmall magnet is likely to be more preferable. PTX-MNPs-PLO2000 holds great promise in the application of magnetic accumulation, target drug delivery, and thermal therapy.

Superparamagnetic anisotropic nano-assemblies with longer blood circulation in vivo: a highly efficient drug delivery carrier for leukemia therapy.

Leukemia, unlike solid tumors, has no definite shape and spreads throughout the whole circulatory system, therefore the therapy of leukemia requires medication to stay longer in the circulatory system. Anisotropic nanoparticles, showing longer blood circulating life than that of isotropic nanoparticles reported in previous research, meet the demands of leukemia therapy. Based on this strategy, superparamagnetic anisotropic nano-assemblies (SANs) were fabricated and loaded with vincristine (VCR) to form VCR-SANs. When compared to the same dose of VCR-loaded isotropic nano-assemblies (SINs), the decrease in the leukocytes count and the positive expression ratio of CD13 in the VCR-SANs group were 19.38% and 16.4%, respectively, which indicated the improved anti-leukemia activity of the VCR-SANs. From the results of the pharmacokinetics study, the VCR-SANs remarkably held the amount of drug removed from the whole body per unit time half of the isotropic group and the concentration of drug in blood plasma against time was 2.1 times the isotropic group, demonstrating the rapid and sustained release behavior and longer blood circulation when combined with the results of in vivo tissue distribution studies. In summary, anisotropic nano-assemblies were found to be more promising than isotropic nano-assemblies via our in vivo and in vitro examinations.

Multi-modal Mn-Zn ferrite nanocrystals for magnetically-induced cancer targeted hyperthermia: a comparison of passive and active targeting effects.

The high performance and increased tumor-targeting accumulation of magnetic nanocrystals (MNCs) are the most important considerations in cancer targeted magnetic hyperthermia (TMH). To achieve these goals, our study was firstly done using well-established fluorescence/magnetic Mn-Zn ferrite MNCs (core size: 14 nm) as multi-modal imaging contrast agents and highly-efficient "heat generators", which were coated with a biocompatible PEG-phospholipid (DSPE-PEG2000) and further modified by a cyclic tripeptide of arginine-glycine-aspartic acid (RGD). By using a mouse model bearing breast carcinoma (4T1), we then systematically compared PEGylated MNCs (MNCs@PEG)- and RGD-PEGylated MNCs (MNCs@RGD)-mediated tumor targeting abilities by intravenous administration. The MNCs@PEG-based passive targeting could successfully accumulate at the tumor due to the enhanced permeability and retention (EPR) effects, but the non-targeted localization might make the MNCs@PEG "leaking" from larger pores of tumor fenestrated vascular networks. Our designed MNCs@RGD, simultaneously functionalized with PEG and RGD ligands, might promote a synergistic effect including efficient tumor vasculature active targeting and EPR-mediated passive targeting, improving total MNC concentration and retention time in tumor tissues. By combining fluorescence/magnetic resonance (MR)/thermal multi-modal imaging-guided diagnostics and continuous TMH treatment under an alternating current magnetic field (ACMF, 2.58 kA m(-1), 390 kHz), the tumor surface could be heated to approximately 43-44 °C based on the MNC-mediated repeated injections. Sufficient temperature elevation induced the apoptosis of tumor cells, and inhibited the tumor angiogenesis. Compared with MNCs@PEG, the active MNCs@RGD-based tumor targeting MR image was significantly more efficient due to both the higher and long-lasting tumor accumulation, but its antitumor efficacy was not obviously improved in the TMH treatments. To achieve a singularly promising tumor TMH therapy, a greatly increased MNC content in tumor was needed. This insight indicated that not only the tumor vasculature targeting, but also the active tumor cells targeting of MNCs should receive considerable attention in future clinical TMH therapy application.

Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo.

The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers. In this study, we investigated the role of MDM2 in epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms in breast cancer cells in vitro and in vivo. The results showed that up-regulation of MDM2 in MCF-7 cells altered the cell morphology to a mesenchymal phenotype. Knockdown of MDM2 in MDA-MB-231 cells altered the cell morphology to the epithelial phenotype. In addition, overexpression of MDM2 increased the expression of N-cadherin and Vimentin and decreased the expression of E-cadherin, at both the mRNA and protein levels, in vitro and in vivo. Conversely, down-regulation of MDM2 decreased the expression of N-cadherin and Vimentin, and increased the expression of E-cadherin in vitro. Furthermore, MDM2 up-regulated both the mRNA and protein expression of Snail in vitro and in vivo. Knockdown of Snail almost abolished MDM2 induced EMT in vitro. Finally, we found that MDM2 expression correlated with EMT markers and Snail: Snail expression was inversely associated with E-cadherin in human breast cancer samples. Our findings demonstrated that MDM2 induces EMT by enhancing Snail expression in vitro and in vivo. Thus, MDM2 may be a potential target for therapy against human metastatic breast cancer.

Integrated pharmacokinetics and biodistribution of multiple flavonoid C-glycosides components in rat after oral administration of Abrus mollis extract and correlations with bio-effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus mollis, a commonly used traditional Chinese medicine in China and other Asia countries, has been used clinically to prevent and treat hepatitis and alcoholic liver disease for decades. MATERIALS AND METHODS: A modified HPLC-MS method was developed for the determination of vicenin-2 (AM-I), isoschaftoside (AM-II), and schaftoside (AM-III) of AM extract (AME) in rat plasma and tissues (heart, liver, spleen, lungs, and kidneys). Following oral administration of AME to rat at a dose of 200mg/kg, the concentrations of AM-I, II and III in plasma and tissues were quantified. An integrated double peak pharmacokinetics model was used to fit the concentration-time curves. The effects of drug on the bile flow and toe swelling of rats induced by carrageenan were also studied. RESULTS: The limit of quantitation of this modified HPLC-MS method decreased from 25 to 5ng/mL for plasma and from 100 to 10ng/g for tissue. These concentration-time curves show two successive maximum concentrations. The results of integrated double peak pharmacokinetics in this paper indicated that the three flavonoid C-glycosides may be absorbed by two sites of intestine in vivo. These results of bile flow and toe swelling showed a significant correlation between the pharmacokinetics and pharmacodynamics. CONCLUSIONS: The novel integrated double peak pharmacokinetic approach to studying the holistic pharmacokinetic properties of traditional Chinese medicine has been successfully developed and validated using AM as a model drug. This study would be a useful guide for the holistic double peak pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.

2, 3-dimercaptosuccinic acid-modified iron oxide clusters for magnetic resonance imaging.

Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2 O3 @DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2 O3 @DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2 O3 @DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2 O3 @DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2 O3 @DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex(®) . Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2 O3 @DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2 O3 @DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases.

High-performance PEGylated Mn-Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics.

An effective magnetic nanocrystals (MNCs)-mediated theranostics strategy as a combination of simultaneous diagnostics and heating treatment of tumors by using magnetic resonance imaging (MRI) and alternating current magnetic field (ACMF) is successfully developed. In this strategy, we had firstly synthesized a well-established Mn-Zn ferrite MNCs coated with PEG-phospholipids (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol copolymers, DSPE-PEG2000). The monodisperse PEGylated MNCs with core-shell structure (15 nm) exhibited excellent performance, such as high magnetism of 98 emu g(-1) Fe, relaxivity coefficient (r2) of 338 mm(-1) s(-1), and specific absorption rate (SAR) value of 324 W g(-1) Fe. It was proved that the obtained MNCs with an average diameter of 48.6 nm can drastically minimize the recognition and phagocytosis of macrophages, simultaneously improve their biocompatibility in vitro. These advantages endowed them with efficient passive targeting ability in vivo for prominent tumor MRI and magnetically induced heating when exposed to ACMF, based on enhanced permeability and retention (EPR) effects. To ensure sufficient accumulation of MNCs within tumors for targeted hyperthermia, we described the use of MNCs with a well-tolerated intravenous single dose of 18 mg Fe/kg mouse body weight, achieving repeatedly injection and hyperthermia within a subcutaneous breast cell carcinoma mouse model. With an ACMF of 12 A at 390 kHz, the tumor surface sites could be heated to approximately 43 °C in 30 min based on MNCs-mediated intravenous injections. The long-lasting hyperthermia could effectively induce the apoptosis of tumor cells, inhibit the angiogenesis of tumor vessels, and finally suppress the tumor growth within a certain period of time.

Photocatalytic degradation of Rhodamine B by microwave-assisted hydrothermal synthesized N-doped titanate nanotubes.

Microwave-induced nitrogen-doped titanate nanotubes (NTNTs) were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), Zeta potential analysis, specific surface area (SBET), and UV-Visible spectroscopy. TEM results indicate that NTNTs retain a tubular structure with a crystalline multiwall and have a length of several hundred nanometers after nitrogen doping. XRD findings demonstrate that the crystalline structure of NTNTs was dominated by anatase, which is favored for photocatalytic application. The Ti-O-N linkage observed in the XPS N 1s spectrum is mainly responsible for narrowing the band gap and eventually enhancing the visible light photoactivity. FT-IR results demonstrated the existence of H3O⁺, which could be excited by photo-generated holes to form hydroxyl radicals and degrade environmental pollutants. After sintering at 350°C, the UV-Vis absorbance edges of NTNTs significantly shift to the visible-light region, which indicates N atom doping into the nanotubes. Photocatalytic degradation of Rhodamine B (RhB) via NTNTs show good efficiency, with pseudo first-order kinetic model rate constants of 3.7 × 10⁻³, 2.4 × 10⁻³ and 8.0 × 10⁻4 sec⁻¹ at pH3, 7, and 11, respectively.

[Study on preparation of breviscapine liposomes and chemicophysical properties].

OBJECTIVE: To prepare breviscapine pro-liposomes and evaluate its properties and stability, as well as its interaction with the mimic-membrane. METHODS: Breviscapine liposomes were prepared by thin film-lyophilization method. Phase inversion temperature was measured by electrical conductance method and coalescence kinetics was studied. Water/n-octanol trans-membrane diffusion model was designed to study the dynamic distribution behavior between two phases, through the determination of diffusion rate of breviscapine and liposomes. RESULTS: The phase inversion temperature was 63 degrees C, the activity energy for coalescence was 14.66 kJ/mol. The results suggested that breviscapine from liposomes staying on the interface were found more than the breviscapine infusion. CONCLUSION: Breviscapine liposomes prepared with thin film-lyophilization method have good physicochemical properties and stability, which is beneficial to treatment.

MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9.

The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors. The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r²â€Š= 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown.

Wettability determined by capillary rise with pressure increase and hydrostatic effects.

Capillary rise is the basis of some methods that are widely applied for the determination of contact angles as well as wettabilities of small particles. The equivalent hydraulic radius r(d) in the Classical Washburn equation is assumed to be particle-specific. But it seems that r(d) is not always constant when the type of liquids is different. The new equation with the pressure increment and the hydrostatic effects are theoretically derived based on the Washburn equation, so contact angles of small particles can be measured experimentally independently of r(d). The result shows the validity of the proposed method, and therefore, it becomes possible to accurately measure the wettability of small particles.