Fate and potential ecological risk of rare earth elements in 3000-year reclaimed soil chronosequences.

The introduction of anthropogenic inputs into natural systems may lead to enduring alterations in the innate characteristics of Rare Earth Elements (REEs). Against this backdrop, the evolutionary processes and environmental drivers of REEs in soil remain uncertain. A 3000-year soil chronosequence with uniform parent material was established in reclaimed farmland along the Yangtze River, reconstructing, for the first time, the dynamic processes of REE accumulation and fractionation over a long-time scale. Analysis of 122 soil samples showed REE concentrations ranging from 146.00 to 216.56 µg/g. Based on reclamation duration, three significant stages of REE evolution were identified: natural leaching, rapid accumulation, and stable accumulation with differentiation. Reclaimed soil after 3000 years exhibited a 14.1 % increase in REE concentrations compared to fresh sediments, attributed to anthro -pedogenic processes. Moreover, Heavy Rare Earth Elements (HREEs) accumulated faster than Light Rare Earth Elements (LREEs), particularly in deeper soils (60-100 cm), where HREE concentrations rose by 34.3 %, mainly due to acidic environments promoting HREE fixation. Additionally, the potential ecological risk posed by REEs heightened with reclamation duration, with HREEs exhibiting a sensitivity of 83 % to 94 %. Our findings stress the urgency of carefully monitoring exogenous REEs introduced through anthropogenic activities, particularly HREEs.

Geochemical behavior and source analysis of rare earth elements in intensive agriculture soils through high-resolution sampling.

Rare Earth Elements (REEs) are crucial for a low-carbon economy but overuse pollutes ecosystems. Studying their behavior and source in agricultural soils provides vital insights for soil management. To address this, we collected an extensive dataset comprising 2901 topsoil and 733 subsoil samples from an agriculturally dominant region in eastern China, characterized by uniform parent material. This comprehensive dataset enabled a thorough examination of the geochemical behavior and sources of REEs in the region. Our findings revealed the feasibility of utilizing La, Ce, and Y to predict ΣREE, LREE, HREE, and LREE/HREE ratios, thereby enhancing the REEs database for eastern China. The average ΣREE concentration in the study area measured 193.0 µg/g, with LREEs constituting 89 % of this total, representing a slight enrichment relative to the Upper Continental Crust. Notably, the electron-donating ability of Ce exhibited a correlation with Mn, indicating its potential as an indicator of redox reactions. The results obtained through structural equation modeling and random forest analysis identified Al, Ti, and K as the most influential environmental factors affecting ΣREE concentrations. Additionally, the indirect impact of K on ΣREE through pH was established. The strong correlation observed between major elements and Heavy Rare Earth Elements (HREEs) shed light on the mechanisms responsible for the notable fractionation of REEs in topsoil. Furthermore, our investigation underscored the substantial influence of pedogenetic processes on the enrichment and leaching of REEs. Source analysis pinpointed significant contributors to REEs, including fertilizers, pesticides, domestic wastewater, coal fly ash, and the native soil parent material. In conclusion, our study emphasizes the pressing need for judicious control of anthropogenic REE inputs. This step is pivotal not only for ensuring the sustainable utilization of soil but also for ultimately safeguarding ecosystems and environmental quality.

JNK regulates the Nrf2/NQO1-ARE pathway against Microcystins-Induced oxidative stress in freshwater mussel Cristaria plicata.

In response to stress, cells can utilize several processes, such as the activation of the Nrf2/Keap1 pathway as a critical regulator of oxidative stress to protect against oxidative damage. C-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in regulating the NF-E2-related nuclear factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. NAD(P)H quinone redox enzyme-1 (NQO1), a downstream target gene of the Nrf2 pathway, plays a vital role in removing peroxide and providing resistance to oxidative injury. We found that microcystins (MCs) stimulated CpNrf2 to express and increase anti-oxidative enzyme activities in a previous experiment. In our current study, the full-length cDNAs of JNK and NQO1 from Cristaria plicata (designated CpJNK and CpNQO1) were cloned. The relative levels of CpJNK and CpNQO1 were high in hepatopancreas. Upon MCs induction, the relative level of CpNQO1 was increased, whereas that of CpJNK was decreased significantly. In contrast, CpNrf2 knockdown upregulated the expression of CpJNK mRNA and phosphorylation of CpJNK protein (Cpp-JNK), but inhibited CpNQO1 expression. Additionally, we found that JNK inhibitor SP600125 stimulated expression of CpNQO1 and CpNrf2 upon exposure to MCs, and we further confirmed that CpNrf2 protein combined with the ARE element in CpNQO1 gene promoter in vitro, and increased CpNQO1-ARE-luciferase activity in a CpNrf2-dependent manner. These findings indicated C. plicata effectively alleviated MC-induced oxidative injury through JNK participated in regulating the Nrf2/NQO1-ARE pathway.

P62/SQSTM1 upregulates NQO1 transcription via Nrf2/Keap1a signaling pathway to resist microcystins-induced oxidative stress in freshwater mussel Cristaria plicata.

Microcystins (MCs) are the most frequent and widely distributed type of cyanotoxin in aquatic systems, and they cause an imbalance of the body's oxidative system. In a previous experiment, we demonstrated that the mollusk Cristaria plicata can protect against MC-induced oxidative damage through the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-related protein-1 (Keap1) pathway. Here, we evaluated whether selective autophagy affects the Nrf2/Keap1a anti-oxidative stress pathway in C. plicata. Full-length cDNA sequences of p62/SQSTM1 from C. plicata (Cpp62) were divided into 2484 bp fragments. From N-terminal to C-terminal, the amino acid sequence of Cpp62 contained PB1 (Phox and Bem1p domain), ZNF (zinc finger domain) chain, LIR (LC3 interacting region) and UBA (ubiquitin-associated domain) domains, but not the KIR (Keap1 interacting region) domain. We confirmed that Cpp62 did not bind to CpKeap1a in vitro, and the relative level of Cpp62 was the highest in the hepatopancreas. Moreover, MCs significantly upregulated the mRNA and protein levels of Cpp62 in the hepatopancreas after CpKeap1a knockdown, whereas Nrf2 upregulated the transcription levels of Cpp62, suggesting that MCs increased Cpp62 expression via the Nrf2/Keap1a signaling pathway. Moreover, Cpp62 and CpNrf2 proteins have a strong affinity for the NQO1 promoter, but MCs inhibited the ability of CpNrf2 and Cpp62 to upregulate luciferase activity. The results show that Nrf2 and the p62 protein induced p62 expression by binding to ARE (antioxidant response element) sequences in the p62 promoter of C. plicata, thereby promoting p62 to resist MC-induced oxidative stress. Therefore, we speculate that MCs induce p62-dependent autophagy in C. plicata, resulting in the inhibition of Nrf2 transcription and Cpp62 promoter activity. These findings help to reveal the mechanism by which the p62-Nrf2/Keap1 pathway mitigates MC-induced oxidative damage in mussels.

Patency and adverse outcomes of sequential vs. individual saphenous vein grafts in coronary artery bypass: A meta-analysis.

Objectives: To undertake a systematic review and meta-analysis of cohort studies to compare the patency and adverse outcomes of sequential and individual saphenous vein grafts (SVGs) in coronary artery bypass grafting (CABG). Methods: We searched PubMed, Embase, and the Cochrane Library for cohort studies. Endpoints for vein graft failure, perioperative and follow-up adverse events were extracted as risk ratio (RR) with 95% confidence intervals (95% CI). Statistical heterogeneity across the studies was examined using the I2 statistic. Potential of publication bias was evaluated quantitatively by the Egger's test. Sensitivity analysis was also performed to assess the robustness of our outcomes. Results: The 15 studies were analyzed, including 22,004 patients, 4,580 grafts, and seven different adverse events under individual or sequential CABG. The sequential group had inferior graft failure (RR = 0.68; 95% CI, 0.60-0.77) and long-term mortality (RR = 0.76; 95%CI, 0.61-0.95), but with an increased risk of perioperative repeat revascularization (RR = 1.58; 95%CI, 1.16-2.14) than the individual group. Conclusion: Taken together, our analysis of the aggregated evidence comparing the sequential and individual saphenous vein grafts for coronary heart disease patients showed that the use of the sequential graft was associated with inferior graft failure and long-term mortality respectively, but with an increased risk of perioperative repeat revascularization. According to our study, both surgical techniques have their own advantages in efficacy and safety, and the selection of surgical techniques should be based on patients and surgeons. Sequential saphenous vein grafts should be more recommended to experienced surgeons in order to both reduce perioperative adverse events and improve long-term patency. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022326992.

Copper-Catalyzed Asymmetric Ring-Opening Reaction of Cyclic Diaryliodonium Salts with Imides.

An efficient copper-catalyzed asymmetric ring-opening reaction of diaryliodonium salts with imides has been developed, affording a wide range of axially chiral 2-imidobiaryl compounds with excellent enantioselectivities and better convertibility. The potential utility of the current method has been supported by the synthesis of two known chiral ligands with better efficiency, which would be of great significance to the development of other catalytic asymmetric reactions.

A highly sensitive and rapid LC-MS/MS method for quantification of bexarotene in mouse plasma and brain tissue: Application to mice pharmacokinetic study.

Emerging evidence has suggested that bexarotene, a nearly 20-year-old skin cancer drug, may be a potential drug candidate to treat Alzheimer's disease (AD) and other neurodegenerative disorders. As described in this study, a highly sensitive and rapid method, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine bexarotene in mouse plasma and brain tissue, was established and validated for the first time. Single-step protein precipitation utilizing methanol solution (containing 0.05 % acetic acid) as precipitation agent was employed to prepare the samples of plasma and brain tissue. Chromatographic separation in gradient elution mode was conducted via an Agilent ZORBAX SB-C18 column (50 mm × 4.6 mm, 5 µm) employing methanol-ammonium acetate buffer (5 mM, pH adjusted to 4.6 with acetic acid) as mobile phase which flowed at 0.45 mL/min. The total run time was 6 min for each sample. Detection through mass spectrometric technique was operated by selected reaction monitoring (SRM) in negative electrospray ionization mode. The method was linear within the range of 10.0-15000 ng/mL for plasma and 10.0-600 ng/mL for brain tissue homogenate with the lower limit of quantification of 10.0 ng/ml. The plasma or tissue homogenate was only required 20 µL. The intra- and inter-day precision were less than 13.8 %, and the RE was between -7.4 % and 3.4 %. The method was applied to investigate the plasma pharmacokinetics and brain distribution of bexarotene in mice after being intragastrically administered with bexarotene at the dosage of 100 mg/kg. The results showed that both brain and plasma concentrations of bexarotene peaked at 1.0 h. Bexarotene was rapidly eliminated with a half-life of 2.0 h.

Cerebral vasospasm resulted in "stent shortening" after pipeline assisted coil embolization for blood blister aneurysms.

ABSTRACT: Blood blister aneurysms (BBAs) are intracranial arterial lesions appearing in nonbranching sites of the supraclinoid internal carotid artery as well as the basilar artery. Endovascular treatment of BBAs is still not well established because of the rarity of these lesions. We report incidences of BBAs with associated vasospasms. Treatment of the BBAs and associate vasospasms with single Pipeline Flex embolization device (PLED) assisted coiling resulted in seemly shorting of the PLEDs in 3 patients.A retrospective analysis of patients with BBAs who were treated with single PLED assisted coiling from July 2018 to October 2019 was conducted. Patients' ethnic and medical records, aneurysmal characteristics, intraoperative-rupture, cerebral vasospasm (CVS), postprocedure contrast filling, follow-up imaging, and results were analyzed. Neurological examination at baseline and outcome based on modified Rankin scale (mRS) at discharge as well as follow-ups were also documented.Six patients consisting of 5 females and 1 male, with a mean age of 48.3 years (range from 34-67) were identified during our analysis. All the BBAs were located in nonbranching site of supra-clinoidal segment of internal carotid artery with a mean neck width of 4.5 mm and mean aneurysm size of 4.23 mm. PLED assisted coiling's were performed in all of them. CVS was observed in 3 patients while 1 patient had an intraoperative-rupture of the BBA. Postprocedure contrast filling was still present in 1 patient. All the patients had good outcomes with discharge and follow-up mRS scores ≤ 2 except 1 patient with mRS score = 3 with aphasia.PLED assisted endovascular coiling is very safe and efficient in treating patients with BBAs. Resolution of CVSs after treatment made the PLEDs seemly shorter. Furthermore, a combination of arterial lengthening after gaining their tensile strength back and radical expansion of the PLED could account for the shortening.

Institutional experience of in-stent stenosis after pipeline flow diverter implantation: A retrospective analysis of 6 isolated cases out of 118 patients.

ABSTRACT: Pipeline embolization devices (PLEDs) are flow diverting stents that have exhibited be safe and efficient in the treatment of complex aneurysms. Nevertheless, in-stent stenosis (ISS) has been reported as one of the cardinal complications associated with PLED. The association of wall malapposition and ISS in patient treated with PLED has not been reported.A retrospective study was conducted to identify patients with ISS after implantation of PLED as treatment for intracranial aneurysms from April 25, 2018 to April 24, 2019. Incidence of ISS and its associated causes such as sharp change of the PLED, distal wall malapposition, inconsistent compliance between parent artery as well as the PLED occlusion due to intimal hyperplasia and vessel tortuosity. Assessment of conservative treatment and retreatment outcomes of ISS were documented.In all, 6 ISS cases were identified by 2 independent neurointerventionalists out of 118 aneurysm patients treated with PLED. Thus, the incidence rate of ISS in patients treated with PLED was as low as 5% at our institution compared to other studies. The follow-up time for detection of ISS ranged from 6 to 12 months after implantation. Several combinations of reasons such as sharp change of the PLED, distal wall malapposition, inconsistent compliance between parent arteries as well as PLED occlusion due to intimal hyperplasia and vessel tortuosity accounted for the causes of ISS during our analysis. Conservative treatment with a combination of antiplatelet during follow-ups did not resolve the ISS in our study probably due to associated underlying factors above.

Potential hypoglycemic effect of acetophenones from the root bark of Cynanchum wilfordii.

Three new acetophenones, named cynwilforones A-C (1-3), together with cynandione A (4) were isolated from the root bark of Cynanchum wilfordii (Maxim.) Hemsl. Their structures were deduced based on spectroscopic analysis and chemical methods. Compounds 1 and 4 exhibited potential hypoglycemic effects through inhibition of hepatic gluconeogenesis by down-regulating the expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. This is the first report that acetophenones from the root bark of C. wilfordii possesses potential hypoglycemic activity in vitro.

Efficacy evaluation of reteplase in a novel canine acute pulmonary thromboembolism model developed by minimally invasive surgery and digital subtraction angiography.

PURPOSE: In order to evaluate the thrombolytic effects of reteplase in pulmonary thromboembolism (PTE), we developed a novel canine PTE model. The efficacy of reteplase against PTE in comparison to alteplase was clarified for the first time, and this PTE model could be further applied to studies of novel thrombolytic therapies. PATIENTS AND METHODS: Twenty-four dogs were divided into four groups: sham operation, vehicle, alteplase, and reteplase. Autologous thrombi/saline were injected into the pulmonary artery, and thrombolytic agents were administrated. Thrombus formation and dissolution were monitored by real-time digital subtraction angiography (DSA), and pulmonary pressures were measured simultaneously. Blood coagulation, blood gas, hematology, and histopathologic examinations were used as subsidiary methods. RESULTS: The canine PTE model was established with a significant decrease of blood flow and ~75% blocking area. Administration of reteplase (0.6 mg/kg) resulted in effective thrombus dissolution with a recovery of over 80% blood flow, as effective as alteplase (1.6 mg/kg). Correspondingly, the elevated pulmonary systolic, diastolic, and mean arterial pressures declined to the normal level. Blood coagulation was changed by reteplase, with a dramatic elongation of prothrombin time, activated partial thromboplastin time, and thrombin time, even longer than alteplase. In contrast to the vehicle group, no obvious pathological changes were found in the two thrombolytic groups. Hematological, blood biochemical, and blood gas results also indicated that reteplase had no adverse reactions in this PTE model. CONCLUSION: Reteplase proved to be an effective and safe therapy for PTE for the first time, and a small dosage of reteplase exerted an efficacy comparable to the routine dosage of alteplase. Our findings indicated the potential of reteplase as clinical treatment against PTE. This technically innovative, stability- and validity-proved canine PTE model developed by minimally invasive surgery and DSA resembled major clinical features. This may further facilitate our understanding of thrombotic disorders and development of prophylactic and therapeutic approaches.

Management of tunneled-cuffed catheter-related right atrial thrombosis in hemodialysis patients.

OBJECTIVES: Catheter-related right atrial thrombosis (CRAT) is an underreported but potentially life-threatening complication associated with the use of tunneled-cuffed catheters among hemodialysis (HD) patients. Because little is known about the evidence-based guidelines for the optimal management of CRAT among HD patients, this article reports findings based on 20 patients diagnosed with CRAT after catheter replacement and anticoagulation treatment. METHODS: The article retrospectively reviews the hospital records of 20 HD patients treated in the West China Hospital with diagnosis of CRAT from March 2013 to May 2016. Once CRAT was diagnosed, tunneled-cuffed catheters were exchanged over a guidewire in situ and the locations of the new catheter tips were adjusted to be away from the original sites. Immediately after the insertion of a new tunneled-cuffed catheter and at the end of each HD session, both ports of the catheters were locked with unfractionated heparin solution. Patients younger than 70 years of age were treated with warfarin at a target International Normalized Ratio of 1.5 to 1.9, whereas those older than 70 years were treated with dual antiplatelet therapy. All patients were on regular dialysis without thrombolysis or thrombectomy. RESULTS: During the follow-up, two patients died of gastrointestinal massive hemorrhage and one died of acute myocardial infarction. No fatal pulmonary embolism or other CRAT complication-related deaths were observed. A total of eight patients had complete dissolution of CRAT, and 12 patients had reduction in thrombi size. CONCLUSIONS: Maintenance of HD by replacing catheters and providing oral anticoagulation/antiplatelet therapies may be an effective strategy for treating HD patients with CRAT.

Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus.

BACKGROUND: The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus. METHODS: A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone). Enhanced computed tomography/magnetic resonance images were repeated 4 weeks after the procedure to assess the response. Overall survival and complications were assessed until the patient died or was lost to follow-up. RESULTS: Median survival was 10.5 months in the treatment group (2.4 ± 1.7 courses) and 3.9 months in the control group (1.9 ± 1 courses) (P = 0.001). Patients in the treatment group had better overall survival (at 3, 6 and 12 months, respectively), compared to patients in the control group (90.3% vs. 59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of portal vein tumor thrombus regression was higher in the treatment group (93.1%) than in the control group (32.1%) (P < 0.001). CONCLUSIONS: Based on the results of this study, transcatheter chemoembolization combined with intra-arterial ethanol embolization may be more effective than transcatheter chemoembolization alone for treating hepatocellular carcinoma with portal vein tumor thrombus. Intra-arterial ethanol embolization for treating portal vein tumor thrombus is safe, feasible and prolongs overall survival.

CT-Guided Percutaneous Sclerotherapy for Low-Flow Retrobulbar Intraconal Venous Malformations.

BACKGROUND AND AIMS: Until now, no study has focused exclusively on low-flow retrobulbar intraconal venous malformations (RIVMs) which may require treatment due to cosmetic defect, pain, and visual dysfunction. The treatment for RIVMs which surround the optic nerve remains challenging. This case series aimed to evaluate the technical feasibility, effectiveness, and safety of percutaneous sclerotherapy with polidocanol for low-flow RIVMs, using local anesthesia. METHOD: This is a prospective, non-comparative, single-center, interventional case series. All patients signed informed consent forms. Seven patients with RIVMs were treated with percutaneous sclerotherapy with polidocanol/air foam using CT guidance. Primary endpoints are reduction in the volume of RIVMs and pain relief assessed by visual analog scale (VAS). Secondary endpoints are exophthalmos and recording adverse events obtained in clinical follow-up during outpatient visits. RESULTS: Results revealed that the mean volume of RIVMs was decreased from 12.05 ± 6.35 cm3 preoperatively to 1.56 ± 0.43 cm3 postoperatively, (p = 0.005), with a mean decrease of 87.05%. The intraocular pressure was decreased from 14.19 ± 2.99 to 11.79 ± 1.25 mmHg, (p = 0.043). The mean VAS score was decreased from 3.43 ± 2.37 preoperatively to 1.29 ± 0.76 postoperatively, (p = 0.023). The exophthalmos score was decreased from 1.75 ± 0.27 to 1.34 ± 0.31 cm, (p = 0.005). All patients were satisfied with the treatment, which did not leave a postoperative scar. CONCLUSIONS: The results of percutaneous intralesion injection of polidocanol for RIVMs are encouraging. The present results suggest that this method could be a safe and effective treatment option for patients with RIVMs.

Percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue for advanced pancreatic carcinoma: Case Report.

RATIONALE: The aim of this study was to determine the effectiveness of intratumoral injection of chemotherapeutics in improving the quality of life and survival of patients with pancreatic carcinoma. PATIENT CONCERNS: We present a case series of 5 patients with unresectable pancreatic adenocarcinoma. DIAGNOSES: Patients diagnosed with unresectable poorly differentiated pancreatic ductal adenocarcinoma by intraoperative frozen biopsyor percutaneous biopsy. INTERVENTIONS: Five patients with unresectable pancreatic adenocarcinoma received a computed tomography-guided percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue. OUTCOMES: Mean overall survival was 16.2 ±â€Š3.7 months. Local control rates were 100% and 80% at postoperative 3 and 6 months, respectively. Mean Visual Analogue Scale pain score decreased from 7.2 ±â€Š.84 preoperatively to 2 ±â€Š1.22 at postoperative 4 weeks. There were no complications associated with the procedure. LESSONS: Percutaneous intratumoral injection of gemcitabine plus cisplatin mixed with fibrin glue for advanced pancreatic may be safe and effective.

Temporal analysis of blood-brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke.

Blood-brain barrier (BBB) disruption plays an important role in pathophysiological progress of ischemic stroke. However, our knowledge of the dynamic change of BBB permeability and its mechanism remains limited. In the current study, we used a non-human primate (NHP) MCAO model and a serial CSF sampling method that allowed us to determine the dynamic change of BBB permeability by calculating the CSF/serum albumin ratio (AR). We showed that AR increased rapidly and significantly after ischemia, and the fold increase of AR is highly correlated with the infarction size during the subacute phase. Moreover, we determined the temporal change of MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in CSF and serum. Each MMP and TIMP showed different change patterns when comparing their values in CSF and serum. Based on the longitudinal dataset, we showed that the fold increase of MMP-9 in serum and CSF are both correlated to infarction size. Among the measured MMPs and TIMPs, only MMP-2, MMP-13, and TIMP-2 in CSF correlated with AR to some extent. Our data suggest there is no single MMP or TIMP fully responsible for BBB breakdown, which is regulated by a much more complicated signal network and further investigations of the mechanisms are needed.

Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation.

A series of AG014699 derivatives containing a novel scaffold of 2,3-dihydro-1H-[1,2]diazepino[4,5,6-cd]indole-1,4(6H)-dione were synthesized and evaluated for their inhibitory activities toward PARP-1 enzyme and two cell lines, MCF-7 cells and the BRCA1-deficient MDA-MB-436 cells. Our results demonstrated that of all AG014699 derivatives synthesized in this work, compounds 6 and 7 showed strong PARP-1 inhibitory activity (IC50=3.5 nM and 2.4 nM, respectively), only four and three times less potent than AG014699. Compound 6 also had significantly cell inhibitory activity against both MCF-7 cells (CC50=25.8 µM) and the BRCA1-deficient MDA-MB-436 cells (CC50=5.4 µM), nearly as good as AG014699, indicating that it can be a promising compound for further evaluation.

[Digital subtract arteriographic characteristics of carotid artery, vertebral artery, subclavian artery and renal artery in type 2 diabetic patients with lower extremities peripheral arterial disease].

OBJECTIVE: To investigate angiographical characteristics of carotid, vertebral, subclavian, and renal arteries in the type 2 diabetic patients with lower extremities peripheral arterial disease (LEPAD). METHODS: There were 104 type 2 diabetic patients with LEPAD recruited in this study, who received digital subtract arteriography (DSA). Ankle-brachial index (ABI) assessment was also performed in 50 participants. Dependent upon the stenosis degree of vertebral artery, subclavian artery and renal artery measured by DSA, the patients were divided into normal group (stenosis < or = 50%) or pathological group(stenosis > 50% or blocked lesions). The angiographic features of carotid, vertebral, subclavian, and renal arteries were analyzed and the relationship between arterial stenosis and ABI was explored. RESULTS: DSA results of 104 patients showed that the most common lesion in the arteries was plaque. The stenosis degrees of 51%-74% and 75%-99% were most commonly observed in renal artery, with incidence of 22.1% and 5.8%, respectively. Arterial occlusion was most commonly observed in vertebral artery, with incidence of 27.9%. The patients with stenosis or occlusion of arteries had lower ABI (P = 0.000), and the patients with stenosis or occlusion of vertebral and renal arteries also had lower ABI (P = 0.003 and 0.02, respectively), compared with those without stenosis. ABI < 0.9 indicated higher risk of stenosis or occlusion of vertebral and renal arteries (P = 0.008 and 0.047 respectively). Between the patients with subclavian arterial stenosis and those without this artery stenosis, there was no statistical significant difference observed in ABI level. CONCLUSION: Type 2 diabetic patients with LEPAD can affect multiple arteries, showing plaque formation, multi-segmental stenosis and occlusion of arteries. The patients with ABI < 0.9 have higher risk of multiple arterial stenosis or occlusion lesions.

[Effect of total alkaloid of Sophora alopecuroides on SW480 cells and Balb/c nude mice tumor xenograft].

OBJECTIVE: To study the anti-tumor effect of total alkaloid of Sophora alopecuroides (TASA) on human colon adenocarcinoma SW480 cells and Balb/c nude mice tumor xenograft. METHODS: The effect of TASA on cell proliferation was assessed using MTT assay and the cell apoptosis was detected using Annexin V-FITC apoptosis assay. The nude mouse model bearing transplanted solid tumor SW480 was established. The changes of the volume and weight of the tumor were determined after treatment the mice with TASA. Fluorescence quantitative PCR was used to detect Caspase-3, Caspase-9 and BCL-2 mRNA expressions in the tumor. RESULTS: TASA inhibited the proliferation of SW480 cells in a dose- and time-dependent manner. The apoptotic rate of cells was the best when the concentration of TASA was 0.92 mg/mL at 48 hours. The volume and weight of the tumor xenograft in TASA groups were decreased when compared with those of the control group. The results of RT-PCR showed that TASA activated the pro-apoptotic Caspase-3 and Caspase-9 and lowered expressions of BCL-2. CONCLUSION: TASA can inhibit the growth of SW480 cells and the growth of transplanted solid tumor of human SW480 cell line, the mechanism of which involves the effect of Caspase-3, Caspase-9 and BCL-2 expression.

[Digital subtract arteriographic (DSA) characteristics of lower extremities and ankle-brachial index in patients with diabetic feet].

OBJECTIVE: To evaluate the Digital Subtract Arteriography (DSA) characteristics of lower limb arterial diseases in patients with diabetic feet and to explore the correlation between DSA and Ankle-brachial index (ABI). METHODS: Fifty-two patients with diabetic feet were recruited in this study. ABI and DSA of bilateral lower extremities were examined to assess the severity of vasculopathy. The relationship between ABI and DSA was analyzed. RESULTS: ABI values for 91 lower extremities were obtained, with a mean of 0.73 +/- 10.43 (0.15-1.97), among which 19.8% ranged from 0.9 to 1.3, 69.2% were less than 0.9, and 11% were more than 1.3. Based on the integrated angiographic images, the arteries with < or = 50% degree of stenosis, 50%-99% degree of stenosis and occlusion comprised 49.5%, 22%, and 28.5% for femoral artery; 79.1%, 14.3%, and 6.6% for popliteal artery; 25.3%, 8.8%, and 65.9% for anterior tibial artery; 29.7%, 14.3%, and 56% for posterior tibial artery; 25.3%, 20.9%, and 53.8% for peroneal artery; and 54.9%, 14.3%, and 30.8% for dorsal pedis artery. Forty (50.5%) limbs had three or more above-mentioned arteries occluded simultaneously. The average vascular score was 8.5 +/- 4.3 with a range between 0 and 18. The spearman correlation analysis showed that ABI inversely correlated with artery stenosis score (r = -0. 588, P < 0.05). CONCLUSION: Arterial diseases of lower extremities in patients with diabetic feet are wide-spread, ranging from femoral artery to the dorsal pedis artery. Multiple segments of arteries are involved. Severe stenosis and occlusion are more common in anterior and posterial tibial arteries, and peroneal artery.