The anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology and molecular docking / 中国药理学通报

Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment. Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database. The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network. Then the component-target-disease network diagram was constructed. The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets. AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum. Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR. Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets. Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1. Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked. In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells. Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway. Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.

Mitigating COVID-19 outbreak via high testing capacity and strong transmission-intervention in the United States

Most models of the COVID-19 pandemic in the United States do not consider geographic variation and spatial interaction. In this research, we developed a travel-network-based susceptible-exposed-infectious-removed (SEIR) mathematical compartmental model system that characterizes infections by state and incorporates inflows and outflows of interstate travelers. Modeling reveals that curbing interstate travel when the disease is already widespread will make little difference. Meanwhile, increased testing capacity (facilitating early identification of infected people and quick isolation) and strict social-distancing and self-quarantine rules are most effective in abating the outbreak. The modeling has also produced state-specific information. For example, for New York and Michigan, isolation of persons exposed to the virus needs to be imposed within 2 days to prevent a broad outbreak, whereas for other states this period can be 3.6 days. This model could be used to determine resources needed before safely lifting state policies on social distancing.

Ziprasidone Injection for Agitation in Schizophrenic Patients：A Meta-Regression Analysis / 中山大学学报(医学科学版)

@#【Objective】To evaluate the efficacy of ziprasidone injection and the related influencing factors for treating agitation in schizophrenic patients based on published literature in English or Chinese. 【Methods】We searched PubMed， EMBASE， Web of Knowledge， Cochrane Library， Wanfang data， Chinese Journal Full- Text Database（CJFD），Chinese Biomedical Literature Database（CBMdisc）and VIP Chinese Technology Periodical Database（VIP）. The Consolidated Standards of Reporting Trials（CONSORT）statement was used as a criterion for screening and assessing the literature. Meta-analysis and meta-regression were conducted by using STATA. With the effect size as the dependent variable and sex，age，baseline PANSS scale total score and oral antipsychotics as the covariates ，the meta- regression model was analyzed. 【Results】The Grades of Recommendation ，Assessment ，Development and Evaluation（GRADE） approach was employed to rate the overall quality of evidence. A total of 14 studies（5 in English and 9 in Chinese）were included in meta analysis and meta regression. The samples were ，respectively，1 197 and 1 149 at baseline and after treatment. Random effect Meta analysis showed that ziprasidone injection had significant efficacy in the treatment of agitation symptoms［SMD=2.04，95%CI（1.47，2.61），P = 0.000］. Meta regression revealed that the efficacy was related to baseline PANSS scores（t = 5.57 ，P = 0.011）and oral antipsychotics（t = 4.07 ，P = 0.027），but irrelevant to age（t = 0.74，P = 0.539）and language published（t = -0.57，P = 0.625）. The efficacy was better in female patients than that in male patients （t = -2.95 ，P = 0.060）. 【Conclusion】 Ziprasidone injection has significant efficacy in schizophrenia patients with agitation symptoms and the efficacy may be enhanced in those patients with higher baseline PANSS score and added with oral antipsychotics.

Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Electroconvulsive treatment for geriatric depression: a systematic review of randomized clinical trials / 上海交通大学学报（医学版）

Objective·To explore the clinical effectiveness and safety of electroconvulsive therapy (ECT) in elderly patients with depression.Methods·Searches were made in PubMed,EMBase,Web of Knowledge,CNKI,Wanfang,VIE CBMDisc databases and etc.CONSORT (Consolidated Standards of Reporting Trials) statement were used to assess the methodological quality of the studies.RevMan and STATA were used to do meta analysis.Results·Ten studies were included in this systematic review.The studies which used Hamilton depression rating scale (HAMD,n=5) and Montgomery-(A)sberg depression rating scale (MADRS,n=3) to access depressed symptom were analyzed.Sample size was 306 and 290 before and after treatment,respectively.The depressive symptoms were significantly improved after ECT treatment estimated by either HAMD (Z=6.39,SMD=3.64,P=0.000) or MADRS (Z=15.47,SMD=2.12,P=0.000).There was no difference of Mini-mental State Examination (MMSE) scores before and after the treatment (Z=1.47,P=0.140).The incidence of adverse events of headache,confusion,drowsiness,nausea and vomiting was more than 5％.Conclusion·Depressed symptoms are significantly improved in geriatric depression after ECT.The overall cognitive impairment is not obvious,but headache and disturbance of consciousness are common.

Research on magnetoacoustic tomography with magnetic induction reconstruction based on improved time inversion algorithm / 医疗卫生装备

Objective To develop a new algorithm to reconstruct the distribution of acoustic sources of magnetoacoustic tomography with magnetic induction(MAT-MI)in the acoustic inhomogeneous media,which is developed on the basis of generalized finite element method (GFEM) and modified time inversion algorithm. Methods The acoustic and acoustic coupling theory and the basic equations of acoustics were used to study the forward and inverse problems of the acoustic inhomogeneous concentric sphere magneticacoustic coupling model. The solution of acoustic non-uniform media wave equation based on GFEM was proposed.The method solved the problem of acoustically inhomogeneous media sound source reconstruction and conductivity reconstruction.At the same time,the distribution of velocity was reconstructed by rotating the pairs of transducers and the time reversal algorithm. Results The proposed algorithm could accurately reconstruct the acoustic source distribution in acoustic inhomogeneous media,and could obtain the distribution of sound velocity during the reconstruction of sound source and recover the image well. Conclusion The proposed algorithm had its feasibility and effectiveness verified,and gains advantages in MAT-MI reconstruction of acoustic inhomogeneous media.

Efficacy of crizotinib for 28 cases of advanced ALK-positive non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.</p><p><b>METHODS</b>Twenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.</p><p><b>RESULTS</b>Among the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.</p><p><b>CONCLUSIONS</b>Crizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.</p>

[In vitro interaction of deferiprone with cellular membrane transporters of hOCTs and hOAT1].

OBJECTIVE: To develop a LC-MS/MS method for determination of deferiprone in cell lysate and to study the potential interaction between deferiprone and hOCTs or hOAT1 transporters in vitro. METHODS: The determination was performed on an Agilent Eclipse Plus C18 column(3.5 µm, 2.1 mm×50 mm).The gradient mobile phase was composed of solvent A:0.1% formic acid in water, and B:0.1% formic acid in acetonitrile. The mass spectrometer with an electrospray interface was operated in positive ion mode with multiple reaction monitoring (MRM) scan mode monitored the ion pair of deferiprone at m/z 140→96, or phenacetin at m/z 180→110. The effects of deferiprone on the accumulation of typical substrates of hOCTs and hOAT1 were evaluated by MDCK-hOCTs and MDCK-hOAT1 cells respectively. The accumulation of deferiprone was also investigated in MDCK-hOCTs cells and mock cells with or without typical inhibitors. RESULTS: The standard curve was linear over the range of 5-300 nmol/L. The assay recovery of deferiprone was above 94%, and the intra-day precision (RSD) was less than 2.0%. The accumulation of MPP(+) in MDCK-hOCTs cells with 300 µmol/L deferiprone were 73.5%, 87.1% and 70.4%, respectively. The uptake of deferiprone in MDCK-hOCTs and mock cells did not show significant difference. Deferiprone of 100 µmol/L did not significantly affect the accumulation of 6-CF in MDCK-hOAT1 cell. CONCLUSION: The method is sensitivity and suitable for the determination of deferiprone in cell lysate. Deferiprone can significantly inhibit hOCT1 and hOCT3, but has no effects on hOCT2 and hOAT1. hOCTs may not play a major role in the transport of deferiprone.

In vitro interaction of deferiprone with cellular membrane transporters of hOCTs and hOAT1 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a LC-MS/MS method for determination of deferiprone in cell lysate and to study the potential interaction between deferiprone and hOCTs or hOAT1 transporters in vitro.</p><p><b>METHODS</b>The determination was performed on an Agilent Eclipse Plus C18 column(3.5 μm, 2.1 mm×50 mm).The gradient mobile phase was composed of solvent A:0.1% formic acid in water, and B:0.1% formic acid in acetonitrile. The mass spectrometer with an electrospray interface was operated in positive ion mode with multiple reaction monitoring (MRM) scan mode monitored the ion pair of deferiprone at m/z 140→96, or phenacetin at m/z 180→110. The effects of deferiprone on the accumulation of typical substrates of hOCTs and hOAT1 were evaluated by MDCK-hOCTs and MDCK-hOAT1 cells respectively. The accumulation of deferiprone was also investigated in MDCK-hOCTs cells and mock cells with or without typical inhibitors.</p><p><b>RESULTS</b>The standard curve was linear over the range of 5-300 nmol/L. The assay recovery of deferiprone was above 94%, and the intra-day precision (RSD) was less than 2.0%. The accumulation of MPP(+) in MDCK-hOCTs cells with 300 μmol/L deferiprone were 73.5%, 87.1% and 70.4%, respectively. The uptake of deferiprone in MDCK-hOCTs and mock cells did not show significant difference. Deferiprone of 100 μmol/L did not significantly affect the accumulation of 6-CF in MDCK-hOAT1 cell.</p><p><b>CONCLUSION</b>The method is sensitivity and suitable for the determination of deferiprone in cell lysate. Deferiprone can significantly inhibit hOCT1 and hOCT3, but has no effects on hOCT2 and hOAT1. hOCTs may not play a major role in the transport of deferiprone.</p>

Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Seventy patients aged 70 years or over with stage IIIb-IV NSCLC were equally and randomly divided into pemetrexed plus cisplatin group (PC) and gemcitabine plus carboplatin group (GC). Patients in the PC group received pemetrexed (PEM) 500 mg/m(2) on day 1, and carboplatin (CBP) AUC5 on day 1 for 21-day cycle. Patients in the GC group received gemcitabine 1000 mg/m(2) on days 1 and 8, CBP AUC5 on day 1 for a 21-day cycle.</p><p><b>RESULTS</b>In the PC and GC groups, CR 0 and 0, PR 10 and 8, response rates 28.6% and 22.9% were observed, respectively. There was no statistically significant difference between the two groups (χ(2) = 0.299, P = 0.584). The 1-year and 2-year survival rates of the PC and GC groups were 48.6% vs. 45.7% and 11.4% vs. 11.4%, respectively, with a median survival of 11.00 and 10.00 months, without a statistically significant difference between the two groups (χ(2) = 0.01, P = 0.919). Regarding toxicities, the incidences of neutropenia/thrombocytopenia, nausea and vomiting (grade III ∼ IV) in the GC group were significantly higher than those in the PC group (P < 0.05). According to the observer scale of lung cancer symptoms, the post-treatment scores improved in both the two groups, and with no significant difference between them (P > 0.05).</p><p><b>CONCLUSIONS</b>PC and GC show similar efficacy for elderly NSCLC patients, however, the toxicities in PC patients are lower than those in GC patients. Thus, pemetrexed combined with carboplatin is an effective chemotherapeutic regimen for advanced NSCLC in elderly patients.</p>

Role of GDNF in the behavior and cognitive impairment of mice induced by chronic stress and aging / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of chronic stress on the spatial learning-memory and the role of glial cell line-derived neurotrophic factor (GDNF) of prefrontal cortex (PFC) and hippocampus (HP) in different age mice.</p><p><b>METHODS</b>The chronic stress model mice in 21 days with multiple chronic unpredictable stressors were applied. The spontaneous behavior and spatial learning-memory ability of mice were tested, using Open field and Morris water maze task, and the expression of GDNF in HP and PFC were detected by immunohistochemical method.</p><p><b>RESULTS</b>Compared with young mice, the spontaneous behaviors were significantly decreased and the spatial learning-memory function were significantly decreased (P < 0.05, P < 0.01) in aged mice. The GDNF expression in the CA3, DG of HP and PFC were significantly reduced in aged mice (P < 0.05, P < 0.01). After chronic stress, the spontaneous behaviors were remarkably decreased and the ability of spatial learning-memory of the stress group mice were significantly decreased (P < 0.05, P < 0.01) compared with those of the control group mice. The expression of GDNF in HP and PFC were remarkably reduced (P < 0.05, P < 0.01) in stress group mice. The aged stress mice had more serious changes after chronic stress.</p><p><b>CONCLUSION</b>The brain aging and chronic stress in mice causes behavioral changes and the damage of spatial learning-memory function, and which may be nearly related to the expression of GDNF in HP and PFC.</p>

[Anticancer effect of triptolide-polyethylenimine-cyclodextrin in vitro].

OBJECTIVE: To develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro. METHODS: Triptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining. RESULTS: Triptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining. CONCLUSION: Triptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

[Characteristics of cationic polymers PEI-CyD, PEI-PHPA, PEE-PHPA and PEI25kD in vitro and in vivo].

OBJECTIVE: To study the characteristics of cationic polymers polyethylenimine-ß-cyclodextrin (PEI-CyD), polyethylenimine-poly-(3-hydroxypropyl)-aspartamide (PEI-PHPA), N,N-Dimethyldipropylenetriamine-Bis(3-aminopropyl)amine-aspartamide (PEE-PHPA) in vitro and in vivo. METHODS: PEI-PHPA, PEI-CyD and PEE-PHPA were synthesized and the chemistry structure of PEI-PHPA, PEI-CyD and PEE-PHPA was confirmed by (1)H-NMR. The particle size and zeta potential of these polymers were measured, and capacity of plasmid DNA condensation was tested. The inhibition of COS-7, A549, HEK293 and C6 cells was measured by MTT assay. The transfection efficiency was determined in HEK293 cell lines. The toxicity, tissue distribution and transfection efficiency of cationic polymers were tested in vivo. RESULTS: When the N/P of polymers/DNA at 30, the particle sizes were close 250 nm and the zeta-potential were near 35 mv. They were able to condense DNA at N/P ratio < 5. The MTT assay showed that the IC(50) of PEE-PHPA was 21.5, 20.2, 7.30 and 37.1 µg/ml, and that of PEI25kD was 15.8, 18.3, 11.4 and 36.7 µg/ml in C6, COS-7, A549 and HEK293cell lines, respectively. The cell viability of PEI-CyD and PEI-PHPA in above cell lines was over 60%. They had high transfection efficiency in HEK293 cell lines. The LD(50) of PEI25Kd, PEI-CyD, PEI-PHPA and PEE-PHPA in vivo was 19.50, 100.4, 521.2 and 630.0, respectively by intraperitoneal (ip) injection. The contractions of these polymers were higher in kidney than in other organs and tissues.PEE-PHPA had slight effect on kidney and liver function. CONCLUSION: PEE and PEI25kD have higher transfection efficiency and higher toxicity; while PC and PHPA-PEI have lower toxicity and higher transfection efficiency to be used as non-viral gene vector.

Correlation between spiral CT preoperative staging of pancreatic cancer and PTEN and COX-2 expression.

BACKGROUND/AIMS: The aim of the present study was to evaluate the efficacy of TNM staging of pancreatic cancer by multilayer spiral computed tomography (MSCT) and its correlation with tissue PTEN and COX-2 expression. METHODOLOGY: Fifty-two patients with pancreatic cancer had MSCT for TNM staging and PTEN and COX-2 expression were detected in pancreatic cancer tissue by immunohistochemistry. RESULTS: The total accuracy of MSCT was 79.5% in diagnosis of TMN staging of pancreatic cancer, with 73.1% for T staging (70.0% in T1, 65.0% in T2, 82.4% in T3 and 80.0% in T4), 76.9% for N staging (81.8% in N0 and 73.3% in N1) and 88.5% for M staging (89.7% in M0 and 84.6% in M1). The PTEN expression was not related to tumor size (p>0.05) but correlated with T staging, lymph node metastasis and clinical staging (p<0.05). COX-2 expression was not related to tumor size and T staging (p>0.05) but correlated with lymph node metastasis and clinical staging (p<0.05). CONCLUSIONS: TNM staging of pancreatic cancer was accurately conducted by MSCT-thin-layer-imaging. The correlation with PTEN and COX-2 expression implied that combined application of both approaches can improve the accuracy of diagnosis and staging in pancreatic cancer.

Anticancer effect of triptolide-polyethylenimine-cyclodextrin in vitro / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.</p><p><b>METHODS</b>Triptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.</p><p><b>RESULTS</b>Triptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.</p><p><b>CONCLUSION</b>Triptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.</p>

Characteristics of cationic polymers PEI-CyD, PEI-PHPA, PEE-PHPA and PEI25kD in vitro and in vivo / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the characteristics of cationic polymers polyethylenimine-β-cyclodextrin (PEI-CyD), polyethylenimine-poly-(3-hydroxypropyl)-aspartamide (PEI-PHPA), N,N-Dimethyldipropylenetriamine-Bis(3-aminopropyl)amine-aspartamide (PEE-PHPA) in vitro and in vivo.</p><p><b>METHODS</b>PEI-PHPA, PEI-CyD and PEE-PHPA were synthesized and the chemistry structure of PEI-PHPA, PEI-CyD and PEE-PHPA was confirmed by (1)H-NMR. The particle size and zeta potential of these polymers were measured, and capacity of plasmid DNA condensation was tested. The inhibition of COS-7, A549, HEK293 and C6 cells was measured by MTT assay. The transfection efficiency was determined in HEK293 cell lines. The toxicity, tissue distribution and transfection efficiency of cationic polymers were tested in vivo.</p><p><b>RESULTS</b>When the N/P of polymers/DNA at 30, the particle sizes were close 250 nm and the zeta-potential were near 35 mv. They were able to condense DNA at N/P ratio < 5. The MTT assay showed that the IC(50) of PEE-PHPA was 21.5, 20.2, 7.30 and 37.1 μg/ml, and that of PEI25kD was 15.8, 18.3, 11.4 and 36.7 μg/ml in C6, COS-7, A549 and HEK293cell lines, respectively. The cell viability of PEI-CyD and PEI-PHPA in above cell lines was over 60%. They had high transfection efficiency in HEK293 cell lines. The LD(50) of PEI25Kd, PEI-CyD, PEI-PHPA and PEE-PHPA in vivo was 19.50, 100.4, 521.2 and 630.0, respectively by intraperitoneal (ip) injection. The contractions of these polymers were higher in kidney than in other organs and tissues.PEE-PHPA had slight effect on kidney and liver function.</p><p><b>CONCLUSION</b>PEE and PEI25kD have higher transfection efficiency and higher toxicity; while PC and PHPA-PEI have lower toxicity and higher transfection efficiency to be used as non-viral gene vector.</p>

[Percutaneous transcather closure of atrial septal defect guided by transthoracic echocardiography and transesophageal echocardiography].

OBJECTIVE: To evaluate the reliability of the combined use of TTE and TEE in guiding percutaneous closure of atrial septal defect. METHODS: A total of 120 patients were recruited, all accepting TTE and TEE examinations before surgery. The release of ASD occluders was guided by TTE. The patients were divided into two groups. Patients in Group A received ASD occluders with > or = 24 mm diameter. Group B received ASD occluders with < 24 mm diameter. Each group comprised patients with and without retroaortic rim. The patients were followed up with TTE and ECG examinations 24 h, 1, 3 and 6 months after the procedure. RESULTS: ASD closure was successful for 94% and 100% of the patients in group A and group B, respectively. The difference of the ASD diameter measured by TEE and TTE was (2.7 +/- 2.8) mm in group A and (1.7 +/- 2) mm in group B, P < 0.05. The ASD diameter measured by TEE had a (4.87 +/- 1.10) mm and (4.2 +/- 0.80) mm difference with the diameter of ASD occluders for patients in Group A and Group B, respectively (P < 0.05). The ASD diameter measured by TTE had a (7.51 +/- 2.72) mm and (5.89 +/- 2.26) mm difference with the diameter of ASD occluders for patients in Group A and Group B, respectively (P < 0.05). The ASD diameter measured by TEE had a greater correlation coefficient with the ASD occluder diameter than that measured by TTE. The ASD diameters measured by TEE(x1) and TTE(x2) were both linearly correlated with the ASD occluder diameter(y). There was no difference in the successful rate of ASD closure between the patients with and without deficient retroaortic rim. In group A, the procedure failed in 4 patients; misalignment of the ASD occlude occurred in one patient; one patient suffered from second degree type II atrio-ventricular block; one patient had ischemic cerebral stroke. No such complications occurred in group B. CONCLUSION: The combined use of TTE and TEE before the intervention procedure and the release of ASD occluder guided by TTE enables high successful closure rate with little complication. It is an effective and safe method. It can be performed in patients with deficient retroaortic rim.

Clinical observation of bone graft and impaction on posterior interbody fusion for lumbar instability / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical effect and indication of bone graft and impaction on posterior interbody fusion for lumbar instability.</p><p><b>METHODS</b>From January 2001 to July 2008, 95 patients with lumbar instability were treated by bone graft and impaction on posterior interbody fusion. Including 41 males and 54 females, the age from 45 to 76 years old with an average of 59 years. There were 68 cases with single level, 22 cases with two-level, 5 cases with three-level in patients, which were 127 intervertebral space altogether. The neural canal and affected side nerve root were decompressed thoroughly during operation. Resected the disc from the affected side and erased the cartilage to plate extensively combined with pedicle screw fixation, and impaction on interbody fusion with the excisional vertebral plate bone was achieved. To assess the improvement of the patients' symptom, sign, and JOA scores pre and post operatively. Meanwhile, the changes of intervertebral height from the lumbar radiographs were measured and the degrees of interbody bone fusion were evaluated according to SUK method.</p><p><b>RESULTS</b>All the 95 patients were followed up from 12 to 90 months with the mean of 44.8 months. All the clinical symptom were improved significantly or disappeared completely. All the 127 intervertebral space achieved good bone fusion. There was no displacement of bone graft and severe complication happened. According to the radiograph, all the intervertebral heights were increased obviously. The mean JOA score improved from 11.3 +/- 3.3 preoperative to 25.1 +/- 2.8 at 8 weeks postoperative; achieved 24.8 +/- 3.2 with followed up at the last time (P < 0.001).</p><p><b>CONCLUSION</b>Bone graft and impaction on posterior interbody fusion was one of the most effective methods for the lumbar instability. It has extensive range of application, and it's suitable for senile lumbar degeneration instability especially.</p>