Prevalence and genetic variation of the M, N, and S2 genes of feline coronavirus in Shandong Province, China.

Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.

Multisequence magnetic resonance imaging-based radiomics models for the prediction of microsatellite instability in endometrial cancer.

PURPOSE: To evaluate the performance of multisequence magnetic resonance imaging (MRI)-based radiomics models in the assessment of microsatellite instability (MSI) status in endometrial cancer (EC). MATERIALS AND METHODS: This retrospective multicentre study included 338 EC patients with available MSI status and preoperative MRI scans, divided into training (37 MSI, 123 microsatellite stability [MSS]), internal validation (15 MSI, 52 MSS), and external validation cohorts (30 MSI, 81 MSS). Radiomics features were extracted from T2-weighted images, diffusion-weighted images, and contrast-enhanced T1-weighted images. The ComBat harmonisation method was applied to remove intrascanner variability. The Boruta wrapper algorithm was used for key feature selection. Three classification algorithms, logistic regression (LR), random forest (RF), and support vector machine (SVM), were applied to build the radiomics models. The area under the receiver operating characteristic curve (AUC) was calculated to compare the diagnostic performance of the models. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the models. RESULTS: Among the 1980 features, Boruta finally selected nine radiomics features. A higher MSI prediction performance was achieved after running the ComBat harmonisation method. The SVM algorithm had the best performance, with AUCs of 0.921, 0.903, and 0.937 in the training, internal validation, and external validation cohorts, respectively. The DCA results showed that the SVM algorithm achieved higher net benefits than the other classifiers over a threshold range of 0.581-0.783. CONCLUSION: The multisequence MRI-based radiomics models showed promise in preoperatively predicting the MSI status in EC in this multicentre setting.

Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis.

BACKGROUND: Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality. AIM: To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit (ICU) patients. METHODS: PubMed, EMBASE, the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30, 2022. The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver. 12.1. Additionally, subgroup analyses and meta-regression were conducted to assess heterogeneity. RESULTS: A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis. The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%. The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B (PMB)-induced nephrotoxicity. The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval, nephrotoxicity criteria, age, publication year, study quality and sample size, which were confirmed in the univariable meta-regression analysis. Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses. Furthermore, older age, the presence of sepsis or septic shock, hypoalbuminemia, and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity, while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity. CONCLUSION: Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high. It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.

Radiomics based on multisequence magnetic resonance imaging for the preoperative prediction of peritoneal metastasis in ovarian cancer.

OBJECTIVES: To develop a radiomics signature based on multisequence magnetic resonance imaging (MRI) to preoperatively predict peritoneal metastasis (PM) in ovarian cancer (OC). METHODS: Eighty-nine patients with OC were divided into a training cohort including patients (n = 54) with a single lesion and a validation cohort including patients (n = 35) with bilateral lesions. Radiomics features were extracted from the T2-weighted images (T2WIs), fat-suppressed T2WIs, multi-b-value diffusion-weighted images (DWIs), and corresponding parametric maps. A radiomics signature and nomogram incorporating the radiomics signature and clinical predictors were developed and validated on the training and validation cohorts, respectively. RESULTS: The radiomics signature generated by 6 selected features showed a favorable discriminatory ability to predict PM in OC with an area under the curve (AUC) of 0.963 in the training cohort and an AUC of 0.928 in the validation cohort. The nomogram, comprising the radiomics signature, pelvic fluid, and CA-125 level, showed more favorable discrimination with an AUC of 0.969 in the training cohort and 0.944 in the validation cohort. Net reclassification index with values of 0.548 in the training cohort and 0.500 in the validation cohort. CONCLUSION: Radiomics signature based on multisequence MRI serves as an effective quantitative approach to predict PM in OC patients. A nomogram of radiomics signature and clinical predictors could further improve the prediction ability of PM in patients with OC. KEY POINTS: • Multisequence MRI-based radiomics showed a favorable discriminatory ability to predict PM in OC. • The nomogram incorporating the radiomics signature and clinical predictors was clinically useful to preoperatively predict PM in patients with OC.

Radiomics derived from dynamic contrast-enhanced MRI pharmacokinetic protocol features: the value of precision diagnosis ovarian neoplasms.

OBJECTIVES: To evaluate the efficiency of 2- and 3-class classification predictive tasks constructed from radiomics features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic (PK) protocol in discriminating among benign, borderline, and malignant ovarian tumors. METHODS: One hundred and four ovarian lesions were evaluated using preoperative DCE-MRI. Radiomics features were extracted from 7 types of DCE-MR images. To explore the differential ability of radiomics between three types of ovarian tumors, two- and three-class classification tasks were established. The 2-class classification task was divided into three subtasks: benign vs. borderline (task A), benign vs. malignant (task B), and borderline vs. malignant (task C). For the 3-class classification task, 104 lesions were randomly divided into training (72 lesions) and validation (32 lesions) cohorts. The discrimination abilities of the radiomics signatures were established with the training cohort and tested with the independent validation cohort. The predictive performance of the task was evaluated by receiver operating characteristic (ROC) curve, calibration curve analysis, and decision curve analysis (DCA). RESULTS: For the 2-class classification task, the combination of PK radiomics signatures model (PK model) showed a good diagnostic ability with the highest area under the ROC curves (AUCs) of 0.899, 0.865, and 0.893 for tasks A, B, and C, respectively. Additionally, the 3-class classification task demonstrated a good discrimination performance with AUCs of 0.893, 0.944, and 0.891 for the benign, borderline, and malignant groups, respectively. CONCLUSIONS: Radiomics analysis based on the DCE-MRI PK protocol showed promise for discriminating among benign, borderline, and malignant ovarian tumors. KEY POINTS: • Two-class classification predictive task of DCE-MRI PK protocol enabled the classification of 3 categories of ovarian tumors through the pairwise comparison strategy with a perfect diagnostic ability. • Three-class classification predictive task maintained good performance to effectively judge each category of ovarian tumors directly.

Intravoxel Incoherent Motion Imaging in Differentiation Borderline From Malignant Ovarian Epithelial Tumors: Correlation With Histological Cell Proliferation and Vessel Characteristics.

BACKGROUND: The differentiation of borderline from malignant ovarian epithelial tumors (OETs) is difficult based on morphologic characteristics. Diffusion and perfusion information from intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) might be useful for this distinction. PURPOSE: To investigate the potential of IVIM-DWI in discriminating borderline from malignant OETs by correlating with cell proliferation and microvessel density (MVD). STUDY TYPE: Prospective. SUBJECTS: Sixty-six patients with OETs (22 borderline, BOETs; 44 malignant, MOETs) underwent IVIM-DWI before surgery. FIELD STRENGTH: 3.0T IVIM-DWI sequence with 12 b-values (0-1000 sec/mm2 ). ASSESSMENT: Apparent diffusion coefficient (ADC) and IVIM-DWI parameters (diffusion coefficient [D], microvascular volume fraction [f], and pseudodiffusion coefficient [D*]) were measured. Cell proliferation and MVD was determined by immunohistochemical staining of Ki-67 and CD-31, respectively. STATISTICAL TESTS: Mann-Whitney U-test; two-sample t-test; intraclass correlation coefficient; Bland-Altman analysis; receiver operating characteristics (ROC) curves; and Spearman correlation. RESULTS: ADC and D in BOETs was significantly higher than those in MOETs (P < 0.001), while f in BOETs was significantly lower than those in MOETs (P < 0.001). No significant difference was found in D* between borderline and malignancies (P = 0.324). In the differential diagnosis of borderline from malignant OETs; D demonstrated the highest area under the curve (AUC) of 0.951, while ADC and f had a lower AUC of 0.921 and 0.847, respectively. The ADC and D was negatively correlated with cell proliferation (r = -0.682, r = -0.694, respectively, P < 0.001), while f was positively correlated with MVD of the OETs (r = 0.558, P < 0.001). DATA CONCLUSION: IVIM-DWI may be a useful tool for differentiating BOETs from MOETs. D and f could be image biomarkers to reflect histopathological characteristics of cell proliferation and MVD in OETs. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:928-935.

[Effects of acupuncture on carotid intima-media thickness and cerebral blood flow velocity in patients with mild-to-moderate hypertension].

OBJECTIVE: To observe the characteristics of carotid intima-media thickness (IMT) and cerebral blood flow velocity in patients with mild-to-moderate hypertension, and to evaluate the effects of acupuncture on carotid IMT and blood flow velocity of middle cerebral artery and vertebral-basilar artery. METHODS: A total of 240 patients with mild-to-moderate hypertension who met the inclusion criteria were treated with Huoxue Sanfeng acupuncture method proposed by academician SHI Xue-min. The acupoints of Renying (ST 9), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given once a day, five times a week for 3 months. The carotid ultrasonography and transcranial color Doppler were performed before treatment and 3 months after treatment to evaluate the improvements of carotid IMT and brain blood flow velocity. RESULTS: Among 175 patients, 94.3% suffered from impaired carotid IMT. After acupuncture intervention, 7.7%-10.9% patients had improved IMT but 4.6%-6.3% had aggravated carotid IMT. There was no significant difference of carotid IMT before and after treatment (P>0.05). About 50% patients had abnormal intracranial blood flow velocity; after acupuncture intervention, 27.4%-33.3% patients who had the abnormal blood flow velocity had normal one, but 27.0%-52.5% patients who had normal blood flow velocity had abnormal one. After acupuncture intervention, the low-speed blood flow of MCA, VA and BA in female patients aged 41-60 years and the low-speed blood flow of MCA and VA in female patients aged 61-70 years were significantly improved (all P<0.05); the high-speed blood flow of MCA and VA in male patients aged 61-70 years and the high-speed blood flow of VA and BA in female patients aged 41-60 years were significantly decreased (all P<0.05). CONCLUSION: Nearly 95% of patients with mild-to-moderate hypertension had carotid IMT, and about 50% had abnormal blood flow velocity of intracranial artery. The present study failed to found significant effects of acupuncture on carotid IMT, but it shows acupuncture can generally improve the low blood flow velocity in women with mild-to-moderate hypertension.

The efficacy of RGD modified liposomes loaded with vinorelbine plus tetrandrine in treating resistant brain glioma.

Brain glioma is one of the most common and devastating intracranial malignancies with a high mortality. Chemotherapy for brain glioma is not ideal due to blood brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and glioma cell targeting simultaneously. The studies were performed on glioma cells, resistant glioma cells and glioma-bearing mice. Results showed that the constructed liposomes with suitable physicochemical properties could significantly enhance the transport across BBB, obviously accumulate in glioma cells, and exhibit evident capabilities in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced anticancer efficacy could be attribute to the follows: prolonged elimination half-life (7.093 ± 1.311 h); increased AUC0-24 h (28.92 ± 2.66 mg/L*h); transporting across BBB; enhanced cellular uptake; down-regulation on P-gp (0.49 ± 0.06 fold); inducing apoptosis via activating caspase 8, 9, and 3 (2.40 ± 0.22, 3.57 ± 0.29, and 4.33 ± 0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus tetrandrine liposomes may offer a promising therapeutic strategy for treatment of brain glioma.

Matrine exerts inhibitory effects in melanoma through the regulation of miR-19b-3p/PTEN.

Matrine, one of the main alkaloid components extracted from the traditional Chinese herb, Sophora flavescens Ait, has various pharmacological effects, and has been reported to exert antitumor activity in melanoma. In the current study, the molecular mechanisms underlying the inhibitory effects of matrine were investigated in melanoma cell line. It was initially confirmed that matrine inhibited proliferation, invasion and induced apoptosis in human A375 and SK-MEL-2 melanoma cell lines in vitro. Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of microRNA (miR)-19b-3p was significantly increased in melanoma cells and was downregulated by treatment with matrine. Furthermore, downregulated miR-19b-3p exerted effects similar to 500 µg/ml matrine on cell proliferation, invasion and apoptosis. Phosphatase and tensin homolog (PTEN) mRNA was identified as a direct target of miR-19b-3p through bioinformatics analysis and a dual-luciferase reporter assay. Additionally, western blotting and RT-qPCR analysis demonstrated that the expression of PTEN protein and mRNA were increased by the treatment with matrine. Furthermore, silencing of PTEN expression reversed the effects of matrine and miR-19b-3p downregulation in A375 and SK-MEL-2 cells. Taken together, the results indicated that matrine may suppress cell proliferation and invasion and induce cell apoptosis partially via miR-19b-3p targeting of PTEN.

Hyaluronic acid modified daunorubicin plus honokiol cationic liposomes for the treatment of breast cancer along with the elimination vasculogenic mimicry channels.

BACKGROUND: Breast cancer is an alarming global public health problem and a main cause of cancer-related death in women. Systemic chemotherapy is the most widely used treatment for breast cancer. However, current chemotherapy treatments are far from desirable due to poor targeting specificity, severe side effects and vasculogenic mimicry (VM). PURPOSE: Hyaluronic acid (HA)-modified daunorubicin plus honokiol (HNK) cationic liposomes were prepared and characterised for treatment of breast cancer by eliminating VM. METHODS: HA-modified daunorubicin plus HNK cationic liposomes were prepared by a thin-film hydration method. Evaluations were performed on MCF-7 cells and MDA-MB-435S cells, which are human breast cancer cells, and xenografts of MDA-MB-435S cells. RESULTS: In vitro results revealed that the HA-modified daunorubicin plus HNK cationic liposomes enhanced the cellular uptake and destroyed VM channels. In vivo results demonstrated that the liposomes prolonged the circulation time in the blood, obviously accumulated in the tumour region, and enhanced the overall anticancer effects. Action mechanisms were related to down-regulation of VM protein indicators including FAK, EphA2, MMP-2 and MMP-9. CONCLUSIONS: The prepared HA-modified daunorubicin plus HNK cationic liposomes may serve as a promising therapeutic strategy for the treatment of breast cancer.

Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer.

Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin. The action mechanism might be related to regulations on E-cadherin, α5ß1-integrin, TGF-ß1, VEGF and MMP2/9 in breast cancer cells. In vivo, the liposomes displayed a prolonged circulating time, more accumulation in tumor location, and a robust overall antitumor efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice. In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer.

Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.

Antitumor efficacy of Lf modified daunorubicin plus honokiol liposomes in treatment of brain glioma.

Malignant brain glioma is the most common and aggressive type of primary intracranial neoplasm. Regular chemotherapy cannot eradicate brain glioma cells and the residual glioma cells could form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for tumor cell invasion. In addition, the existence of the blood-brain barrier (BBB) restricts most antitumor drugs into brain glioma. In this study, we developed a kind of lactoferrin (Lf) modified daunorubicin plus honokiol liposomes to transport antitumor drugs across BBB, eliminate the VM channels and block tumor cell invasion. The evaluations were performed on BBB model, brain glioma cells and glioma-bearing mice. In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels. Action mechanism studies indicated that Lf modified daunorubicin plus honokiol liposomes could activate apoptotic enzymes caspase 3 as well as down-regulate VM protein indicators (PI3K, MMP-2, MMP-9, VE-Cadherin and FAK). In vivo results displayed the targeting liposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy. Therefore, Lf modified daunorubicin plus honokiol liposomes could be used as a potential therapy for treatment of brain glioma.

Comparative functional neuroanatomy between implicit and explicit memory tasks under negative emotional condition in schizophrenia.

PURPOSE: To evaluate the brain activation patterns in response to negative emotion during implicit and explicit memory in patients with schizophrenia. MATERIAL AND METHODS: Fourteen patients with schizophrenia and 14 healthy controls were included in this study. The 3.0T fMRI was obtained while the subjects performed the implicit and explicit retrievals with unpleasant words. RESULTS: The different predominant brain activation areas were observed during the implicit retrieval and explicit with unpleasant words. CONCLUSION: The differential neural mechanisms between implicit and explicit memory tasks associated with negative emotional processing in schizophrenia.

The efficacy of WGA modified daunorubicin anti-resistant liposomes in treatment of drug-resistant MCF-7 breast cancer.

BACKGROUND: Breast cancer is the most common malignancy and remains a leading cause of cancer-related deaths in female. Chemotherapy failure of breast cancer is mainly associated with multidrug resistance of cancer cells. PURPOSE: The WGA modified daunorubicin anti-resistant liposomes were developed for circumventing the multidrug resistance and eliminating cancer cells. METHODS: WGA was modified on liposomal surface for increasing the intracellular uptake. Tetrandrine was inserted into the phospholipid bilayer for reversing cancer drug-resistance, and daunorubicin was encapsulated in liposomal aqueous core as an anticancer agent. Evaluations were performed on MCF-7 cells, MCF-7/ADR cells and xenografts of MCF-7/ADR cells. RESULTS: In vitro results showed that WGA modified daunorubicin anti-resistant liposomes exhibited suitable physicochemical properties, significantly increased intracellular uptake in both MCF-7 cells and MCF-7/ADR cells, and circumvented the multidrug resistance via inhibiting P-gp. In vivo results demonstrated that the targeting liposomes showed a long-circulatory effect in blood system, and could remarkably accumulate at the tumor location. The involved action mechanisms for the enhanced anticancer efficacy were activation of pro-apoptotic proteins (Bax and Bok), apoptotic enzymes (caspase 8, caspase 9 and caspase 3). CONCLUSION: The established WGA modified daunorubicin anti-resistant liposomes could provide a potential strategy for treating resistant MCF-7 breast cancer.

Targeting vincristine plus tetrandrine liposomes modified with DSPE-PEG2000-transferrin in treatment of brain glioma.

Glioma is the most frequent primary tumor, and the treatment efficiency is unsatisfactory for the obstacle of the blood brain barrier (BBB), the multidrug resistance (MDR) and the properties of cancer cell invasion and vasculogenic mimicry (VM) formation. In this study, a kind of TF modified vincristine plus tetrandrine liposomes was developed to overcome those limitations. In vitro results showed that TF modified vincristine plus tetrandrine liposomes with suitable physicochemical property could enhance the transport across the BBB, increase the cellular uptake, inhibit the MDR, and block the cancer cell invasion and VM channels. In vivo results demonstrated that TF modified vincristine plus tetrandrine liposomes could significantly prolong the circulation time, obviously accumulate in brain tumor location, thus leading to a robust anticancer efficacy in glioma-bearing mice. These data suggest that TF modified vincristine plus tetrandrine liposomes offer a promising strategy for treating brain glioma.

Predictors for Better Blood-Flow Restoration of Long-Segmental Below-the-Knee Chronic Total Occlusions after Endovascular Therapy in Diabetic Patients.

OBJECTIVE: To prospectively investigate predictors for good restoration of blood flow of below-the-knee (BTK) chronic total occlusions (CTOs) after endovascular therapy in diabetes mellitus (DM) patients. MATERIALS AND METHODS: A total of 120 long-segmental (≥ 5 cm) BTK, CTOs in 81 patients who underwent recanalization were included in this study. After angioplasty, blood-flow restoration was assessed using modified thrombolysis in myocardial ischemia grades and classified as good flow (grade 3) and poor flow (grade 1/2). One hundred and six CTOs with successful recanalization were divided into a good flow group (GFG; n = 68) and poor flow group (PFG; n = 38). Multivariate logistic regression analyses were undertaken to determine independent predictors of blood-flow restoration. Receiver operating characteristic curves were constructed to determine the best cutoff value. The prevalence of target-lesion restenosis during follow-up was compared between two groups. RESULTS: Univariate analyses suggested that CTOs in GFG were characterized by lighter limb ischemia (p = 0.03), shorter course of ischemic symptoms (p < 0.01) and lesion length (p = 0.04), more frequent use of intraluminal angioplasty (p = 0.03), and higher runoff score (p < 0.01) than those in PFG. Multivariate regression analyses suggested that distal runoffs (p = 0.001; odds ratio [OR], 10.32; 95% confidence interval [CI]: 4.082-26.071) and lesion length (p < 0.001; OR, 1.26; 95% CI: 1.091-1.449) were independent predictors for good flow restoration. Kaplan-Meier analyses at 12 months showed a higher prevalence of non-restenosis in GFG (p < 0.01). CONCLUSION: Distal runoffs and lesion length are independent predictors for good flow restoration for long-segmental BTK, CTOs in DM patients who receive endovascular therapy.

Intravoxel incoherent motion diffusion-weighted imaging for monitoring chemotherapeutic efficacy in gastric cancer.

AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model. METHODS: IVIM-DWI was performed with 12 b-values (0-800 s/mm(2)) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D(*))] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD(*)%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed. RESULTS: The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTVtreatment% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTVtreatment% = 29.07% ± 10.01% and ΔTVcontrol% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%treatment, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%control, median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7 (P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group (ΔD%treatment, median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group (ΔD%control, median -0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5 (P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up (median, -34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016; -50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008; -49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and -46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points (median, -32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008; -44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008; -59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and -47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis (r s = 0.720, P < 0.001; r s = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D (r s = 0.626, P = 0.001; r s = 0.542, P = 0.005, respectively). Perfusion-related parameters (f and D(*)) were positively correlated to MVD (r s = 0.618, P = 0.001; r s = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor (r s = -0.550, P = 0.004; r s = -0.692, P < 0.001, respectively). CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.

Effects and mechanism of action of ligustrazine on isoprenaline-induced cardiomyocyte hypertrophy.

The aim of the study is to explore the effects and mechanism of the action of ligustrazine on isoprenaline-induced cardiomyocyte hypertrophy. Primary culture of neonatal rat cardiomyocytes was used as the model, and isoprenaline was used to induce cardiomyocyte hypertrophy. Effects of different dosages of ligustrazine polysaccharide on the cardiomyocyte were observed. RT-PCR was used to detect the expression of atrial natriuretic factor (ANP) mRNA, and Western blot analysis was used to detect the CaN protein level in cardiomyocytes. After treating with ligustrazine, the significant increase of MDA content and decrease of SOD activity were inhibited in supernatant. Compared to the control group, ANP mRNA in isoprenaline-treated cardiomyocytes was significantly increased (P < 0.05); compared to the isoprenaline group, ANP mRNA was significantly decreased in all ligustrazine groups (P < 0.01). In all ligustrazine groups, the CaN expression was inhibited in isoprenaline-treated cardiomyocytes in a dose-dependent manner. In conclusion, ligustrazine has protective effects on isoprenaline-induced neonatal rat cardiomyocyte, which may be related to the decrease of CaN expression.

Synthesis and antidiabetic performance of ß-amino ketone containing nabumetone moiety.

We wish to report the further design and improved synthesis that resulted in two series of target molecules, TM-1 and TM-2, with remarkably simplified structures containing ß-amino ketone of discrete nabumetone moiety. These were obtained via a 'one-pot, two-step, three-component' protocol of Mannich reaction with yield up to 97%. A total of 28 out of 31 new compounds were characterized using (1)H NMR, (13)C NMR, ESI MS and HRMS techniques. Studies on their antidiabetic activities, screened in vitro at 10 µg mL(-1) level, indicate that TM-2 possesses peroxisome proliferator-activated receptor activation and α-glucosidase inhibition activity significantly stronger than that of TM-1, and also that of the series B compounds that were previously synthesized by the group. Analysis of the structure-activity relationship points to the sulfanilamide unit as the most probable potent group of ß-amino ketone and, on the basis of which, a tangible strategy is presented for the development of new antidiabetic drugs.