Dynamic Optical Encryption Fueled via Tunable Mechanical Composite Micrograting Systems.

Optical grating devices based on micro/nanostructured functional surfaces are widely employed to precisely manipulate light propagation, which is significant for information technologies, optical data storage, and light sensors. However, the parameters of rigid periodic structures are difficult to tune after manufacturing, which seriously limits their capacity for in situ light manipulation. Here, a novel anti-eavesdropping, anti-damage, and anti-tamper dynamic optical encryption strategy are reported via tunable mechanical composite wrinkle micrograting encryption systems (MCWGES). By mechanically composing multiple in-situ tunable ordered wrinkle gratings, the dynamic keys with large space capacity are generated to obtain encrypted diffraction patterns, which can provide a higher level of security for the encrypted systems. Furthermore, a multiple grating cone diffraction model is proposed to reveal the dynamic optical encryption principle of MCWGES. Optical encryption communication using dynamic keys has the effect of preventing eavesdropping, damage, and tampering. This dynamic encryption method based on optical manipulation of wrinkle grating demonstrates the potential applications of micro/nanostructured functional surfaces in the field of information security.

Metal-Organic Frameworks Corset with a Thermosetting Polymer for Improved Molecular-Sieving Property of Mixed-Matrix Membranes.

Metal-organic frameworks (MOFs) are promising materials for gas separation membranes. However, the framework flexibility affects their molecular-sieving properties. Herein, we restrict the flexibility of zeolitic imidazolate framework-7 (ZIF-7) by controlling its phase transition in mixed-matrix membranes (MMMs), relying on the so-called "space-confinement effect" of a novel thermosetting polymer, poly 2,2'-(p-oxydiphenyl)-5,5'-bibenzimidazole (OPBI) polymer. Compared with the pure OPBI membrane, the optimized membranes containing 30 wt % ZIF-7 with a narrow-pore (np) phase (ZIF-7-II) exhibited a significant improvement in H2/CO2 separation, e.g., the H2/CO2 ideal selectivity increased ∼2.8 times, surpassing the state-of-the-art upper bound of polymeric membranes and exhibited excellent stability at increased pressure and temperature (8 bar, 180 °C).

Clinical characteristics of patients with COVID-19 presenting with gastrointestinal symptoms as initial symptoms: Retrospective case series.

BACKGROUND: A large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms. AIM: To characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms. METHODS: This is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis. RESULTS: Among the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01). CONCLUSION: COVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

miR-32 promotes esophageal squamous cell carcinoma metastasis by targeting CXXC5.

MicroRNA-32 (miR-32) functioned as a tumor oncogene in some cancer, which control genes involved in important biological and pathological functions and facilitate the tumor growth and metastasis. However, the role of miR-32 modulates esophageal squamous cell carcinoma (ESCC) malignant transformation has not been clarified. Here, we focused on the function and the underlying molecular mechanism of miR-32 in ESCC. Results discovered a significant increased expression of miR-32 in ESCC tissues and cells. Downregulation of miR-32 inhibited the migration, invasion, adhesion of ESCC cell lines (EC9706 and KYSE450), and the levels of EMT protein in vitro. In vivo, miR-32 inhibitors decrease tumor size, tumor weight, and the number of metastatic nodules. Hematoxylin and eosin (H&E) results revealed that inhibition of miR-32 attenuate lung metastasis. Immunohistochemistry and immunofluorescence assay showed increased level of E-cadherin and decreased level of N-cadherin and Vimentin with treatment of miR-32 inhibitors. Furthermore, miR-32 targeted the 3'-untranslated region (3'-UTR) of CXXC5, and inhibited the level of mRNA and protein of CXXC5. There is a negative correlation between the expressions of CXXC5 and miR-32. Then, after EC9706 and KYSE450 cells cotransfected with si-CXXC5 and miR-32 inhibitors, the ability of cell migration, invasion, and adhesion was significantly reduced. In addition, the protein expression of EMT and TGF-ß signaling was also depressed. Collectively, these data supply an insight into the positive role of miR-32 in ESCC progression and metastasis, and its biological effects may attribute the inhibition of TGF-ß signaling mediated by CXXC5.

miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2.

BACKGROUND/AIMS: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells. METHODS: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184. RESULTS: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells. CONCLUSION: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC.

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

Prognostic value of chemotherapy in addition to concurrent chemoradiotherapy in T3-4N0-1 nasopharyngeal carcinoma: a propensity score matching study.

PURPOSE: The objective of this study is to evaluate the contribution of induction (IC) or adjuvant (AC) chemotherapy additional to concurrent chemoradiotherapy (CCRT) for patients with T3-4N0-1 nasopharyngeal carcinoma (NPC) in the era of intensity-modulate radiotherapy (IMRT). METHOD AND MATERIALS: We retrospectively reviewed the data on 685 patients with newly diagnosed T3-4N0-1 NPC. Propensity score matching (PSM) method was used to match patients. Survival outcomes between different groups were calculated by Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was adopted to establish independent prognostic factors. RESULTS: In total, 236 pairs were selected from the primary cohort. Univariate analysis revealed 3-year overall survival (OS) (90.8% vs. 90.3%, P = 0.820), distant failure-free survival (DFFS) (87.3% vs. 89.4%, P = 0.896) and locoregional failure-free survival (LRFFS) (95.4% vs. 93.0%, P = 0.311) rates were comparable between CCRT plus IC/AC and CCRT alone groups. Multivariate analysis found that treatment group was not an independent prognostic factors for OS (HR, 0.964; 95% CI, 0.620-1.499; P = 0.869), DFFS (HR, 1.036; 95% CI, 0.626-1.714; P = 0.890) and LRFFS (HR, 0.670; 95% CI, 0.338-1.327; P = 0.250). Further subgroup analysis according to overall stage also obtained similar results. CONCLUSION: Patients with T3-4N0-1 NPC receiving CCRT could not benefit from additional induction or adjuvant chemotherapy in the era of IMRT.

Comparing the efficacy of induction-concurrent with concurrent-adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. RESULTS: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. CONCLUSIONS: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.

Ten-year survival outcomes for patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: An analysis of 614 patients from a single center.

OBJECTIVES: Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT. MATERIALS AND METHODS: Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared. RESULTS: The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P>0.05), respectively, and significantly higher than that of T4 disease (79.3%, P<0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P<0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P<0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome. CONCLUSION: IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease.

Prognostic effect of symptomatic extracranial lesions on survival of recursive partitioning analysis Class III brain metastatic patients treated with stereotactic radiotherapy.

OBJECTIVE: To explore the outcome and prognostic factors of recursive partitioning analysis (RPA) Class III brain metastatic patients treated with stereotactic radiotherapy (SRT). MATERIALS AND METHODS: Fifty-six consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores <70 treated with SRT from January 2008 to October 2013 were involved in the analysis. Twenty-five patients (44.6%) were with symptomatic extracranial lesions (SELs), and the other 31 patients (55.4%) were without SELs. The detailed follow-up data of KPS scores were available in 44 patients. The KPS score drop time (KDT) was calculated as the time between SRT and 10 points drop of KPS scores compared to the baseline. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses. RESULTS: The median overall survival time was 5.0 months (95% confidence interval [CI] 3.42-6.59) for the whole group. In multivariate analysis, the presence of SELs (P = 0.007, relative risk = 4.44, 95% CI 1.036-20.818) was the independent prognosis factor for survival. Median survival time was 3 months for the patients with SELs, 8 months for the patients without SELs. The median KDT of the 44 patients was 3.0 months (95% CI, 1.927-4.073 months). Again only the presence of SELs (P = 0.001, OR = 6.622, 95% CI, 2.108-20.801) was significantly related to KDT in multivariate analysis. The median KDT of the patients with SELs was 1.5 months, which was 5 months for the patients without SELs. CONCLUSION: The presence of SELs was a negative prognosis factor for the survival of RPA Class III brain metastatic patients. If RPA Class III brain metastatic patients were without SELs, SRT may be a reasonable treatment option, but if they had SELs, SRT may not be a reasonable treatment due to the short overall survival time and KDT.

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma.

BACKGROUND: N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). PATIENTS AND METHODS: Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. RESULTS: With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. CONCLUSION: IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.

Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear. OBJECTIVE: The aim of this study was to investigate the effect and mechanism of HMGA2 in inducing invasion and migration in NPC. METHODS: In NPC tissues samples, the association of HMGA2 mRNA expression with clinicopathological characteristics were estimated by real-time quantitative RT-PCR(qRT-PCR). In vitro, following the silencing of HMGA2 in CNE-1 and CNE-2 cell lines, the viability and metastatic ability were analyzed using Cell Counting Kit-8 (CCK8), colony formation assay, and transwell assay. EMT and transforming growth factor-beta (TGFß)/Smad3 signaling pathway-related protein expression changes were evaluated using western blot. RESULTS: HMGA2 was upregulated in NPC cell lines and clinical specimens (P < 0.01), and HMGA2 expression correlated significantly with metastasis (P = 0.02) and disease-free survival of NPC (hazard ratio: 3.52; 95% confidence interval: 1.34-7.79; P = 0.01). In addition, following in vitro knockdown of HMGA2, the aggressiveness of cells was markedly inhibited, Vimentin and Snail level was downregulated and E-cadherin expression was upregulated. Moreover, the expression of key proteins TGFßRII and p-Smad3 of the TGFß/Smad3 signaling pathway was inhibited by the downregulation of HMGA2. CONCLUSION: HMGA2 might maintain EMT-induced invasion and migration through the TGFß/Smad3 signaling pathway in NPC cell lines.

Impact of plasma Epstein-Barr virus-DNA and tumor volume on prognosis of locally advanced nasopharyngeal carcinoma.

This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV-) DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR) amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx), the lymph node lesions (GTVnd), and the total GTV before treatment were 72.46, 23.26, and 106.25 cm(3), respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P < 0.01). The 2-year overall survival (OS) rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P = 1.000), and the disease-free survival (DFS) rates were 94.4% and 80.8% (P = 0.044), respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

HMGA2 is associated with epithelial-mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma.

OBJECTIVE: High-mobility group protein 2 (HMGA2) and epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC. METHODS: Using immunohistochemistry, HMGA2, E-cadherin, and vimentin expression levels were evaluated in NPC (n=124) and non-tumoral inflammatory nasopharynx (n=20) tissues. The association of HMGA2 and EMT markers with clinicopathological characteristics and relationships between the protein levels and overall survival were analyzed. RESULTS: Compared with non-tumorous tissues, HMGA2 and vimentin levels were markedly increased in NPC tissues, whereas decreased E-cadherin levels were observed (P<0.001). Moreover, HMGA2 expression was positively correlated with vimentin levels (r=0.431, P<0.001) and negatively correlated with E-cadherin amounts (r=-0.413, P<0.001) in NPC tissues. The expression of all three proteins correlated significantly with tumor N stage, TNM stage, and 2-year metastasis. Furthermore, significant correlations were found for T stage, N stage, TNM stage, HMGA2, E-cadherin, and vimentin (all P<0.013) with poor prognosis (univariate analysis). However, multivariate analyses showed that only HMGA2 (hazard ratio [HR]: 2.683, 95% confidence interval [CI]: 1.185-6.077, P=0.018) and N stage (HR: 7.892, 95% CI: 2.731-22.807, P<0.001) were independent predictors of poor prognosis. CONCLUSION: These results demonstrated that HMGA2, an independent prognostic factor, may promote NPC progression and metastasis, and is significantly associated with EMT proteins. Therefore, HMGA2 may be considered a potential therapeutic target in NPC.

Fractionated stereotactic radiotherapy for small-cell lung cancer patients with brain metastases.

OBJECTIVE: Patients with small-cell lung cancer (SCLC) are at high risk of developing brain metastases (BM). Fractionated stereotactic radiotherapy (FSRT) alone or combined with whole brain radiation therapy can be used to treat intracranial metastases. This study was aimed to explore FSRT for BM from SCLC. MATERIALS AND METHODS: We retrospectively analyzed 45 patients with BM from SCLC treated with fractionated linear accelerator FSRT. Multivariate analysis was used to determine independent risk factors of overall survival (OS). RESULTS: There were 35 patients treated with salvage FSRT and 10 patients treated with primary FSRT. The median OS was 10 months from the beginning of FSRT and 19 months from diagnosis of BM. The median OS of salvage FSRT group and primary FSRT group was 22 and 10 months from the diagnosis of BM, respectively (P = 0.011); 11 and 8 months from FSRT, respectively (P = 0.828). Recursive partitioning analysis class and the stage of the primary tumor were independent predictors of increased OS (relative risk [RR] = 2.634, P = 0.021 and RR = 2.324, P = 0.0210, respectively). CONCLUSIONS: Salvage and primary FSRT were both effective treatment options for BM from SCLC. Salvage and primary FSRT may have different OS from the time of diagnosis of BM.

Local delivery of vascular endothelial growth factor via nanofiber matrix improves liver regeneration after extensive hepatectomy in rats.

Vascular endothelial growth factor (VEGF) is a potent regulator for liver regeneration following partial hepatectomy. However, intravenous delivery of VEGF has yielded limited success in promoting the regeneration of remnant liver. Here we report a new approach to locally deliver recombinant VEGF from an electrospun poly-ε-caprolactone nanofiber mesh and its effect on improving rat liver regeneration after 70% hepatectomy. After applying the VEGF-releasing nanofiber mesh to the remnant liver lobes following hepatectomy in rats, the fractions of proliferating hepatocytes increased markedly at 48 h and 72 h in comparison with the control group receiving nanofiber meshes without VEGF. The expression of endogenous VEGF in liver tissue was also higher in the VEGF-nanofiber group than those in the control group. These results demonstrate that biodegradable nanofiber meshes offer a convenient and effective approach for local and sustained delivery of VEGF to the remnant liver following partial hepatectomy.

[Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke].

OBJECTIVE: To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population. METHODS: A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene. RESULTS: An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01). CONCLUSION: Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.

Fractionated stereotactic radiotherapy for 136 patients with locally residual nasopharyngeal carcinoma.

BACKGROUND: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). METHODS: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. RESULTS: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. CONCLUSION: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications.

[Effects of extracorporeal membrane oxygenation on hemodynamics in acute right heart failure in dogs].

OBJECTIVE: To investigate the effects of extracorporeal membrane oxygenation (ECMO) on the hemodynamics in dogs with acute right heart failure. METHODS: Ten healthy adult male dogs (weighted 20-25 kg) were randomly divided into two groups: acute right heart failure group (n = 5) and ECMO group (n = 5). Under anesthesia, dogs were underwent thoracotomy, then the catheters were placed in the right atrium, right ventricle, and pulmonary artery, for measuring the relevant pressures, including right arterial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP). The vascular ultrasound probe were placed on the aorta and pulmonary artery for measuring the cardiac output (CO) and pulmonary artery flow rate (QPA). Then, a baseline measurement was acquired. The femoral artery and femoral vein were cannulated and used for the venoarterial extracorporeal membrane oxygenation (VA-ECMO), and then connected to extracorporeal circuit, which was initially primed. The pulmonary artery was progressively ligated to decrease blood flow until QPA was 60%, 40%, and 0% of baseline in both groups. The above flow conditions were respectively maintained for 30 minutes, after which hemodynamic data were collected. RESULTS: The baseline hemodynamic measurements were not different between acute right heart failure group and ECMO group. After ligating the pulmonary artery, compared with baseline, CO (L/min) decreased significantly at 60% and 40% QPA in acute right heart failure group (1.80 ± 0.19, 1.48 ± 0.22 vs. 3.24 ± 0.23, both P < 0.05), and significantly lower than that of ECMO group (60%QPA: 1.80 ± 0.19 vs. 3.24 ± 0.35; 40%QPA: 1.48 ± 0.22 vs. 3.20 ± 0.37, both P < 0.05). CO was not significantly different from baseline in ECMO group at 60%, 40% and 0% QPA (3.24 ± 0.35, 3.20 ± 0.37, 3.12 ± 0.28 vs. 3.44 ± 0.32, all P>0.05). PAP, RAP and RVP (all mm Hg, 1 mm Hg = 0.133 kPa) were significantly elevated in acute right heart failure group at 60% and 40% QPA compared with baseline (PAP: 36.2 ± 5.3, 39.8 ± 5.4 vs. 17.4 ± 2.7; RAP: 11.2 ± 2.8, 12.8 ± 2.6 vs. 4.4 ± 1.7; RVP: 25.6 ± 4.9, 27.8 ± 4.5 vs. 11.6 ± 1.8, all P < 0.05), and significantly higher than those of ECMO group (60%QPA: PAP 36.2 ± 5.3 vs. 23.2 ± 5.2, RAP 11.2 ± 2.8 vs. 6.2 ± 2.3, RVP 25.6 ± 4.9 vs. 15.2 ± 3.5; 40%QPA: PAP 39.8 ± 5.4 vs. 24.4 ± 4.8, RAP 12.8 ± 2.6 vs. 7.0 ± 2.4, RVP 27.8 ± 4.5 vs. 16.8 ± 4.2, all P < 0.05), whereas mean artery pressure (MAP, mm Hg) was significantly lowered compared with that of baseline (81.2 ± 15.8, 62.2 ± 14.4 vs. 128.6 ± 16.4, both P < 0.05), and it was lower than that of ECMO group (60%QPA: 81.2 ± 15.8 vs. 128.0 ± 26.5; 40%QPA: 62.2 ± 14.4 vs. 124.6 ± 25.4, both P < 0.05). At 60%, 40% and 0% QPA in ECMO group, whereas heart rate (HR, beats/min), PAP, RAP and RVP were slightly increased compared with those of baseline (HR: 161.4 ± 14.8, 160.6 ± 13.1, 157.6 ± 11.9 vs. 152.6 ± 14.5; PAP: 23.2 ± 5.2, 24.4 ± 4.8, 25.2 ± 6.2 vs. 18.8 ± 3.4; RAP: 6.2 ± 2.3, 7.0 ± 2.4, 7.6 ± 4.2 vs. 4.6 ± 1.5; RVP: 15.2 ± 3.5, 16.8 ± 4.2, 16.2 ± 3.3 vs. 12.2 ± 2.3), but MAP was slightly decreased (128.0 ± 26.5, 124.6 ± 25.4, 121.2 ± 21.4 vs. 135.8 ± 22.2), however, all differences were not statistically significant (all P>0.05). CONCLUSION: These findings demonstrate that VA-ECMO could be helpful in improving cardiac function, and maintaining stability of hemodynamics in dogs with acute right heart failure.

Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters.

BACKGROUND: To evaluate the efficacy and outcomes of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases > 3 cm. METHODS: From March 2003 to October 2009, 40 patients with brain metastases larger than 3 cm were treated by HSRT. HSRT was applied in 29 patients for primary treatment and in 11 patients for rescue. Single brain metastasis was detected in 21 patients. Whole brain radiotherapy was incorporated into HSRT in 10 patients for primary treatment. HSRT boosts were applied in 23 patients. The diameters of the brain metastases ranged from 3.1 to 5.5 cm (median, 4.1 cm). The median prescribed dose (not including HSRT boosts) was 40 Gy (range, 20-53 Gy) with a median of 10 fractions (range, 4-15 fractions) to the 90% isodose line. The median dose of the boost was 20 Gy (range, 10-35 Gy) in 4 fractions (range, 2-10 fractions). RESULT: The median overall survival time was 15 months. The overall survival and local control rate at 12 months was 55.3% and 94.2%, respectively. Four patients experienced local progression of large brain metastases. Nine patients died of intracranial disease progression. One patient died of radiation necrosis with brain edema. CONCLUSION: HSRT was a safe and effective treatment for patients with brain metastases ranged from 3.1 to 5.5 cm. Dose escalation of HSRT boost may improve local control with an acceptable toxicity.