Base-Controlled Palladium-Catalyzed Intramolecular 'One Substrate - Five Reactions' of 5-Benzyl-1-(2-halobenzyl)-2-phenyl-1H-pyrazol-3(2H)-ones.

Achieving site-selectivity and chemoselectivity is enormously challenging for substrates with multi-reactive sites in organic reactions. One kind of model substrates, 5-benzyl-1-(2-halobenzyl)-2-phenyl-1H-pyrazol-3(2H)-ones with six reactive sites were chosen as the examples to probe their intramolecular four kinds of five reactions including C(sp3 )-H arylation, C(sp2 )-H arylation, reductive Heck reaction, and domino Heck reaction/alkylation of aryl C(sp2 )-H bonds through variation of the reaction conditions. Screening of the reaction conditions showed that the different bases controlled the palladium-catalyzed intramolecular site-selectivity and chemoselectivity of the substrates: (i) Cesium carbonate (Cs2 CO3 ) promoted the benzyl C(sp3 )-H arylation of the substrates providing dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones at 100 °C, and isomerization of the dihydropyrazolo[1,5-b]isoquinolin-2(1H)-ones gave isoquinoline derivatives at a higher temperature (140 °C); (ii) Sodium acetate (NaOAc) mediated the aryl C(sp2 )-H arylation of the substrates affording seven-membered biphenyl N-heterocycles; (iii) Sodium dichloroacetate (Cl2 HCCO2 Na) facilitated occurrence of the reductive Heck reaction of the substrates affording 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones; (iv) Sodium trifluoroacetate (F3 CCO2 Na) assisted performance of the domino Heck reaction/aryl C(sp2 )-H alkylation of the substrates leading to the spiro heterocycles. The 'one substrate - multiple reactions - multiple products' strategy greatly reduces cost, increases diversity of products, provides more opportunity for screening of pharmaceutical molecules, and enriches modern organic synthetic chemistry.

Compare the Diagnostic and Prognostic Value of MLR, NLR and PLR in CRC Patients.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and it is a worldwide challenge. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) had been suggested as markers of CRC, but the role of monocyte-to-lymphocyte ratio (MLR) in CRC patients before surgery and chemotherapy is unclear. The study aimed to compare the diagnosis and prognosis value of MLR, NLR, and PLR in CRC. METHODS: A retrospective study was conducted on 783 patients with histologically confirmed colorectal cancer between 2015 and 2017 in Fujian Medical University Union Hospital. A total of 1,232 healthy age-matched participants were eligible for the study. Receiver-operating characteristic (ROC) analysis was performed to compare the area under the ROC curve (AUC) of MLR, NLR, PLR, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Furthermore, chi-squared test was conducted to determine the prognostic values of MLR, NLR, and PLR. RESULTS: The levels of MLR, NLR, and PLR in CRC patients were significantly higher than those in 1,232 healthy participants. The area under the ROC curves (AUCs) of MLR, CEA, PLR, NLR, and CA19-9 were 0.739, 0.726, 0.683, 0.610, and 0.603, respectively. Moreover, the combined marker of CEA + MLR with an AUC of 0.815 acted as a superior diagnostic marker compared to the other combined markers, including the combined marker of CEA + CA19-9. Furthermore, the level of MLR was associated with tumor size (p = 0.001), and a high level of NLR was significantly correlated with pT stage (p = 0.048) and tumor size (p = 0.004). CONCLUSIONS: The present study shows for the first time that MLR rather than NLR and PLR is the better diagnostic marker for colorectal cancer, and NLR may be a better prognostic marker for CRC patients.

Practical value of three-dimensional high resolution magnetic resonance Vessel Wall imaging in identifying suspicious intracranial vertebrobasilar dissecting aneurysms.

BACKGROUND: Direct evidence of intimal flaps, double lumen and intramural haematomas (IMH) is difficult to detect on conventional angiography in most intracranial vertebrobasilar dissecting aneurysms (VBDAs). Our purpose was to assess the value of three-dimensional high-resolution magnetic resonance vessel wall imaging (3D HRMR VWI) for identifying VBDAs. METHODS: Between August 2013 and January 2016, consecutive patients with suspicious VBDAs were prospectively enrolled to undergo catheter angiography and VWI (pre- and post-contrast). The lesion was diagnosed as definite VBDA when presenting direct signs of dissection; as possible when only presenting indirect signs; and as segmental ectasia when there was local dilation and wall thickness similar to adjacent normal artery's without mural thrombosis. RESULTS: Twenty-one patients with 27 lesions suspicious for VBDAs were finally included. Based on findings of VWI and catheter angiography, definite VBDA was diagnosed in 25 and 7 lesions (92.6%, vs 25.9%, p <  0.001), respectively; possible VBDA in 0 and 20 (0 vs 74.1%), respectively; and segmental ectasia in 2 and 0 (7.4% vs 0%), respectively. On VWI and catheter angiography, intimal flap was detected in 21 and 7 lesions (77.8% vs 25.9%, p = 0.001), respectively; double lumen sign in 18 and 7 (66.7% vs 25.9%, p = 0.003), respectively; and IMH sign in 14 and 0 (51.9% vs 0), respectively. CONCLUSIONS: 3D HRMR VWI could detect direct dissection signs more frequently than catheter angiography. This may help obtain definite diagnosis of intracranial VBDAs, and allow accurate differentiation between dissecting aneurysm and segmental ectasia as well. Further prospective study with larger sample was required to investigate the superiority of HRMR VWI for definite diagnosis of intracranial VBDAs than catheter angiography.

Cysteine-rich protein 61 regulates the chemosensitivity of chronic myeloid leukemia to imatinib mesylate through the nuclear factor kappa B/Bcl-2 pathway.

Although the targeted tyrosine kinase inhibitor imatinib mesylate (IM) has achieved significant responses against CML in the clinical setting, a small proportion of patients fail to respond to IM treatment and their disease continues to progress, indicating resistance to IM therapy. As a secreted extracellular matrix protein, cysteine-rich protein 61 (Cyr61) plays an important role in the resistance of solid tumors to chemotherapy, but its role in CML is unclear. In the present study, we observed that Cyr61 levels were upregulated in the plasma and bone marrow (BM) of patients with CML as well as in K562 cells. This upregulation of Cyr61 significantly decreased IM-induced cellular apoptosis of K562 cells through nuclear factor kappa B/B-cell lymphoma 2 pathways. Inhibition of Cyr61 restored the chemosensitivity of K562 cells to IM both in vitro and in vivo. Thus, our results showed for the first time that Cyr61 plays an important role in regulating the chemosensitivity of CML cells to IM, suggesting that selectively targeting Cyr61 directly or its relevant effector pathways may provide potential value in improving the clinical response of patients with CML to IM treatment.

Superbase-promoted selective carbon-carbon bond cleavage driven by aromatization.

A novel selective carbon-carbon single bond cleavage has been disclosed through the copper-catalyzed reaction of 1-alkyl-3-alkylindolin-2-imine hydrochlorides with substituted 1-(bromomethyl)-2-iodobenzenes leading to fused N-heterocycles. Mechanistic studies showed that the intrinsic drive of aromatization and the action of the superbase derived from sodium tert-butoxide and dimethylsulfoxide were the key factors leading to the carbon-carbon single bond cleavage. Furthermore, the obtained N-heterocycles are indoloquinoline derivatives with wide biological activities.

Morphologic characteristics of severe basilar artery atherosclerotic stenosis on 3D high-resolution MRI.

BACKGROUND: Two-dimensional high-resolution MRI (2D HRMRI) faces many technical challenges for fully assessing morphologic characteristics of inherent tortuous basilar arteries. Our aim was to investigate remodeling mechanisms and plaque distribution in symptomatic patients with basilar artery stenosis on three-dimensional (3D) HRMRI. METHODS: Forty-six consecutive patients with symptomatic basilar artery atherosclerotic stenosis on MRA (70-99%) were enrolled. The remodeling index (RI) was the ratio of vessel area at the maximal-lumen-narrowing (MLN) site to reference vessel area. RI ≥ 1.05 was defined as positive remodeling (PR), RI ≤ 0.95 as negative remodeling (NR), and 0.95 < RI < 1.05 as intermediate remodeling (IR). The remodeling patterns were divided into two groups (PR and non-PR [NR and IR]). The cross-sectional and longitudinal distribution of BA plaques were evaluated. RESULTS: Two patients were excluded because of poor-quality images. Images of 44 patients were available for measurements. PR was found in 23 (52.3%) patients, and non-PR in 21 (47.7%) patients. At the MLN sites, vessel area, wall area, plaque size and percentage of plaque burden of PR group were significantly greater than non-PR group (p < .001). Most plaques (90.9%) of the 44 patients were located at the dorsal, left and right walls. For the longitudinal distribution of plaque, 8 (18.2%) and 36 (81.8%) plaques were located in BA proximal and distal to AICA, respectively. Most plaques (68.2%) were eccentrically distributed. CONCLUSIONS: 3D HRMRI with postprocessing multiple planar reconstruction is able to evaluate the remodeling pattern and plaque distribution of basilar artery atherosclerotic stenosis, which might be used to guide intracranial intervention.

High resolution magnetic resonance imaging in pathogenesis diagnosis of single lenticulostriate infarction with nonstenotic middle cerebral artery, a retrospective study.

BACKGROUND: It is usually difficult to identify stroke pathogenesis for single lenticulostriate infarction with nonstenotic middle cerebral artery (MCA). Our aim is to differentiate the two pathogeneses, non-branch atheromatous small vessel disease and branch atheromatous disease (BAD) by high-resolution magnetic resonance imaging (HR-MRI). METHODS: Thirty-two single lenticulostriate infarction patients with nonstenotic MCA admitted to the China-Japan Friendship Hospital from December 2014 to August 2017 were enrolled for retrospective analysis. National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), atherosclerotic risk factors, imaging features, and the characteristic of MCA vessel wall in HR-MRI were evaluated. RESULTS: MCA plaques were detected in 15(46.9%) patients which implied BAD and 8 of 15 (53.3%) patients had plaques location in upper dorsal side of the vessel wall. Patients with HR-MRI identified plaques had a significantly larger infarction lesion length (1.95 ± 0.86 cm versus 1.38 ± 0.55 cm; P = 0.031) and larger lesion volume (2.95 ± 3.94 cm3 versus 0.90 ± 0.94 cm3; P = 0.027) than patients without plaques. Patients with HR-MRI identified plaques had a significant higher percentage of proximal lesions than patients without plaques (P = 0.055). However, according to the location of MCA plaques, there were no significant differences in terms of imaging features, NIHSS and mRS. CONCLUSION: We demonstrated high frequency of MCA atheromatous plaques visualized in single lenticulostriate infarction patients with nonstenotic MCA by using HR-MRI. Patients with HR-MRI identified plaque presented larger infarction lesions and more proximal lesions than patients without plaque, which were consistent with imaging features of BAD. HR-MRI is an important and effective tool for identifying stroke etiology in patients with nonstenotic MCA.

Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway.

PURPOSE: Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro. METHODS: Skin samples from normal donors and psoriasis vulgaris patients were examined the profile of Cyr61 and IL-8 using immunohistochemistry, real-time PCR and Western blotting. HaCaT cells were treated with Cyr61 and IL-8 expression was analyzed by real-time PCR and ELISA. Signal transduction pathways in Cyr61-induced IL-8 production were investigated by real-time PCR, western blotting, luciferase reporter assay or chromatin immunoprecipitation (ChIP) assay. IMQ-induced psoriasis-like mice were treated with anti-Cyr61monoclonal antibodies (mAb), or IgG1 as a control. RESULTS: We found that Cyr61 was abundant in the epidermis of patients with psoriasis vulgaris and positively correlated with the pathogenesis of skin lesions. Cyr61 induced IL-8 production by keratinocytes in a dose dependent manner. This IL-8 synthesis occurred in an IL-1ß- and TNF-α- independent mode via PI3K, AKT and JNK activation, with binding of enhanced AP-1, C/EBPß and NF-κB to sites located in the IL-8 promoter region. Treatment with anti-Cyr61 mAb led to reduction of MIP-2 level, decreased neutrophil infiltration, and attenuated inflammation in vivo. CONCLUSIONS: Our results not only reveal a novel mechanism illustrating the role of Cyr61 in epidermis pathogenesis but also suggest that therapies targeting Cyr61 may represent a novel strategy in the treatment of psoriasis vulgaris.

Epidemiology of Humanpapilloma virus infection among women in Fujian, China.

BACKGROUND: Human papillomavirus (HPV) infection is the main etiological factor for the development of cervical cancer. Here we assessed the prevalence and distribution of HPV genotypes in Fujian population. METHODS: A total of 8678 women aging from 17 to 84 years olds were recruited from the Fujian Medical University Union Hospital in Fujian Province. Every woman had a face-to-face interview. Cervical samples were collected from each participant and HPV screening was conducted using microarray hybridization. RESULTS: Our study showed that the HPV prevalence in Fujian province was 38.3%. Among the positive individuals, 70.6% were detected for single HPV infection, 29.4% for multiple HPV infections. Further analysis showed that the prevalence of HPV infection significantly increased from 2009 to 2015. The four most common high risk human papillomavirus (HR-HPV) genotypes were HPV16 (8.5%), HPV52 (7.9%), HPV58 (6.2%), HPV 53 (3.5%), collectively accounting for 60.5% of all detected HPV infection. Age subgroup analysis showed two peaks for the frequencies of overall and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 55 years old. CONCLUSIONS: HPV infection is becoming serious in Fujian province, which indicates the imperative to implement a HPV vaccination and screening program for this region.

High carbon dioxide uptake by subtropical forest ecosystems in the East Asian monsoon region.

Temperate- and high-latitude forests have been shown to contribute a carbon sink in the Northern Hemisphere, but fewer studies have addressed the carbon balance of the subtropical forests. In the present study, we integrated eddy covariance observations established in the 1990s and 2000s to show that East Asian monsoon subtropical forests between 20 °N and 40 °N represent an average net ecosystem productivity (NEP) of 362 ± 39 g C m(-2) yr(-1) (mean ± 1 SE). This average forest NEP value is higher than that of Asian tropical and temperate forests and is also higher than that of forests at the same latitudes in Europe-Africa and North America. East Asian monsoon subtropical forests have comparable NEP to that of subtropical forests of the southeastern United States and intensively managed Western European forests. The total NEP of East Asian monsoon subtropical forests was estimated to be 0.72 ± 0.08 Pg C yr(-1), which accounts for 8% of the global forest NEP. This result indicates that the role of subtropical forests in the current global carbon cycle cannot be ignored and that the regional distributions of the Northern Hemisphere's terrestrial carbon sinks are needed to be reevaluated. The young stand ages and high nitrogen deposition, coupled with sufficient and synchronous water and heat availability, may be the primary reasons for the high NEP of this region, and further studies are needed to quantify the contribution of each underlying factor.

Wall thickening pattern in atherosclerotic basilar artery stenosis.

Our aim was to investigate wall thickening (WT) pattern of atherosclerotic basilar artery stenosis with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA), and the relationship with clinical characteristics. Twenty consecutive patients with atherosclerotic basilar artery stenosis were prospectively enrolled. All cross-sectional slices on VISTA images of basilar arteries were assessed, and classified as eccentric or concentric WT. Clinical characteristics and degree of stenosis were compared between the patients with different wall WT pattern. Wall abnormalities were identified in 568 cross-sectional slices in basilar arteries of 20 patients including eccentric WT in 497 (87.5 %) slices, and concentric WT in 71 (12.5 %) slices. In 11 of 20 patients, all the cross-sectional slices (293 slices) showed eccentric WT. In 9 of 20 patients, the cross-sectional slices (275 slices) showed both eccentric WT (204 slices, 74.2 %) and concentric WT (71 slices, 25.8 %). No lesion showed only concentric WT. At the slices of maximum luminal narrowing sites, only one patient showed concentric WT. Symptomatic stenosis was more common in the patients with mixed WT (eccentric and concentric), compared to patients with only eccentric WT (100 vs 54.5 %, p = 0.038). Atherosclerotic basilar artery stenosis could show both eccentric and concentric WT based on each slice analysis. Concentric WT was found in near half of the patients, but tended to locate in minimal slices. No lesion was entirely concentric. Lesions with mixed WT (concentric and eccentric) might represent advanced atherosclerosis with high risk of ischemic event.

Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1ß production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway.

IL-1ß plays a major role in the development of rheumatoid arthritis (RA). We previously showed that Cyr61 participates in RA pathogenesis as a proinflammatory factor. Here, we found that the levels of IL-1ß and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1ß mRNA and proIL-1ß protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1ß was hardly detectable in the supernatant. We also found that the level of adenosine triphosphate (ATP) in SF and ST was significantly increased in RA patients and that the level of IL-1ß in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1ß production in FLS via the AKT-dependent NF-κB signaling pathway, and ATP caused Cyr61-induced proIL-1ß to generate IL-1ß in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1ß production in FLS.

S100A6 mediated epithelial-mesenchymal transition affects chemosensitivity of colorectal cancer to oxaliplatin.

PURPOSE: To investigate the mechanism by which S100 calcium-binding protein A6 (S100A6) affects colorectal cancer (CRC) cells to oxaliplatin (L-OHP) chemotherapy, and to explore new strategies for CRC treatment. METHODS: S100A6 expression was assessed in both parental and L-OHP-resistant CRC cells using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). Lentiviral vectors were utilized to induce the knockdown of S100A6 expression, followed by comprehensive evaluations of cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Additionally, RNA-seq analysis was conducted to identify genes associated with the knockdown of S100A6. RESULTS: Elevated S100A6 expression in CRC tissues correlated with an adverse prognosis in patients with CRC. Higher expression of S100A6 was also observed in L-OHP-resistant CRC cells, which showed enhanced proliferation, migration, invasion, and antiapoptotic capabilities. Notably, the knockdown of S100A6 expression resulted in decreased proliferation, increased apoptosis, and suppression of EMT and tumorigenicity in L-OHP-resistant CRC cells. Transcriptome sequencing reveals a noteworthy association between S100A6 and vimentin expression. Application of the EMT agonist, transforming growth factor ß (TGF-ß), induces EMT in CRC cells. S100A6 expression positively correlates with TGF-ß expression. TGF-ß facilitated the expression of EMT-related molecules and reduced the chemosensitivity of L-OHP in S100A6-knockdown cells. CONCLUSION: In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT.

Characteristics of Atherosclerotic Plaques and Stroke Mechanism in Patients with Border-Zone Infarcts: A High-resolution Magnetic Resonance Imaging Study.

BACKGROUND: Relatively little is known about the plaque characteristics of border-zone infarcts and how they differ between cortical border-zone (CBZ) and internal border-zone (IBZ) infarcts. METHODS: We conducted a retrospective observational cohort study of patients with intracranial atherosclerotic disease who underwent high-resolution magnetic resonance imaging (HR-MRI) examination. Individuals with border-zone infarcts in the middle cerebral artery (MCA) territory, detected by diffusion-weighted imaging, were enrolled. Plaque morphological and compositional parameters of both IBZ and CBZ groups were compared. Independent predictors were identified using a binary logistic regression model, and the sensitivity and specificity of the model were assessed using a receiver operating characteristic curve. Kaplan-Meier survival analysis further explored differences in stroke recurrence between BZ patients with mono or dual antiplatelet therapy. RESULTS: We reviewed 101 symptomatic patients with border-zone infarcts (BZ) within the MCA territory in the study. Out of the patients meeting the imaging eligibility criteria, we detected 34 cases with isolated IBZ, 23 cases with isolated CBZ, and six cases with both IBZ and CBZ infarcts. Those with IBZ infarcts had a higher plaque burden than those without (p < 0.001), and those with CBZ infarcts exhibited a complicated plaque less frequently than those without (37.9% vs 67.6%, p = 0.018). In those with isolated IBZ or CBZ infarcts, plaque burden was independently associated with isolated IBZ infarcts (odd ratio=1.08; 95% CI, 1.02-1.15; p = 0.023). During the median follow-up period of 37 (27, 50) months, 13.8% of patients receiving early dual antiplatelet treatment and 30.4% of those on single antiplatelet therapy experienced stroke recurrence (p = 0.182). CONCLUSION: Intracranial atherosclerotic plaque morphology and composition differ between patients with IBZ and those with CBZ infarcts. Higher plaque burden is more associated with IBZ infarcts.

Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity.

PURPOSE: Chemoresistance is a major challenge for acute lymphoblastic leukemia (ALL) treatment. Cysteine-rich protein 61 (Cyr61) plays an important role in drug resistance modulation of tumor cells, and Cyr61 levels are increased in the bone marrow of patients with ALL and contribute to ALL cell survival. However, the effect of Cyr61 on B cell acute lymphoblastic leukemia (B-ALL) cell chemosensitivity and the regulatory mechanisms underlying Cyr61 production in bone marrow remain unknown. METHODS: Nalm-6 and Reh human B-ALL cell lines were used in this study. Cyr61 levels were assessed using quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The effect of Cyr61 on B-ALL cell chemosensitivity to daunorubicin (DNR) was evaluated using cell viability and flow cytometry analyses. The regulatory mechanisms of Cyr61 production in bone marrow were examined using qRT-PCR and western blot analysis. RESULTS: Cyr61 knockdown and overexpression increased and decreased the chemosensitivity of B-ALL cells to DNR, respectively. Cyr61 attenuated chemotherapeutic drug-induced apoptosis by upregulating B cell lymphoma-2. Notably, DNR induced DNA damage response and increased Cyr61 secretion in B-ALL cells through the ataxia telangiectasia mutated (ATM)-dependent nuclear factor kappa B pathway. CONCLUSION: DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL.

Age and Five-Year Outcomes After Carotid Artery Stenting in Symptomatic Carotid Stenosis: A Retrospective Cohort Study.

BACKGROUND: Several clinical trials have reported that periprocedural risk of carotid artery stenting (CAS) increase with age. China is experiencing one of the most rapid transitions to an aging society, while the clinical outcomes of CAS in real-world China are still limited. The study aimed to compare the periprocedural and an extending 5-year event rates between younger and older patients treated by CAS to testify the safety of CAS in older patients in China. METHODS: This is a single center, retrospective cohort study. Symptomatic patients who underwent CAS from Nov 2011 to June 2014 were retrospectively included in this study, The population was divided into two age groups: <70 and ≥70. The main primary endpoint was stroke, myocardial infarction or death occurring at 30 days, or ipsilateral stroke over 5-year after stenting. RESULTS: A total of 103 symptomatic patients (<70: 68%; ≥70: 32%) with CAS included in the study. During the 30-day period, the rate of primary outcome was 1.0% with only one stroke in patients younger than 70 years old (P = 1.000). After five years, the rate of primary outcome was low (10.9%, 10/92) despite some of the patients had major stroke or underwent bilateral C1 stenting. There was no significant difference in the 5-year rates of the primary outcome between the young and old groups (12.3% vs 7.4%, P = .718). Kaplan-Meier estimates of the proportion of study participants with a primary endpoint showed that there was no significant age-dependent difference of the stroke and death outcome in symptomatic patients. CONCLUSIONS: Age (<70 vs ≥ 70) had no influence on the risk of stroke or death in symptomatic patients either in the short or long term. CAS is an optimal treatment for older patients with cervical carotid artery stenosis, and CAS was safe for those with major stroke or bilateral C1 stenting.

Selection of patients with acute vertebrobasilar artery occlusion for endovascular treatment by magnetic resonance imaging.

Background and purpose: The best method for selecting patients with acute vertebrobasilar artery occlusion (VBAO) who would benefit from endovascular treatment (EVT) is still the key question. This study aimed to assess the efficacy of magnetic resonance imaging (MRI) for selecting patients with acute VBAO for EVT. Materials and methods: A total of 14 patients with suspected acute VBAO on MR angiography (MRA) in the EVT database (from April 2016 to August 2019) were enrolled. Acute Stroke Prognosis Early Computed Tomography Score (ASPECTS) and pons-midbrain index were assessed on diffusion-weighted imaging (DWI). EVT included a stent retriever and a rescue treatment (angioplasty and/or stenting). The proportion of successful reperfusion and favorable functional outcomes (modified Rankin Scale ≤ 3) at 90 days was documented. Results: A total of 11 patients were included in the final analysis. The median DWI-ASPECTS and pons-midbrain index were 7 and 2, respectively. Underlying stenosis was detected in 10 of 11 (90.9%) patients. Balloon angioplasty and/or stenting were used as rescue therapy for five patients and two patients, respectively. A total of nine patients (81.8%) achieved successful reperfusion (mTICI, 2b, or 3). The 90-day mRS score of 0-3 was achieved in six (54.5%) patients. The mortality rate within 90 days was 18.2% (two of 11 patients). Conclusion: DWI plus MRA could help select the patients with acute VBAO for EVT by assessing ASPECTS and the pons-midbrain index. Patients could achieve good reperfusion and favorable functional outcomes.

[Effect of Cyr61 on Imatinib Resistance in Chronic Myeloid Leukemia and Its Mechanism].

OBJECTIVE: To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism. METHODS: Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot. RESULTS: The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61. CONCLUSION: Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.

Studying the imaging features and infarction mechanism of vertebrobasilar dolichoectasia with high-resolution magnetic resonance imaging.

The mechanisms underlying ischemic infarction in patients with vertebrobasilar dolichoectasia (VBD) remain unclear. In this study, we retrospectively analyzed the imaging characteristics of high-resolution magnetic resonance imaging (HR-MRI) in patients with VBD to explore the possible mechanisms of ischemic stroke (IS) in patients with VBD. Patients with VBD were recruited from the HR-MRI database between July 2017 and June 2021. HR-MRI was used to evaluate the diameter, bifurcation height, laterality, arterial dissection, and atherosclerotic plaques of the basilar artery (BA). Transcranial Doppler was used to measure the vertebrobasilar mean velocity (Vm), peak systolic velocity (Vs), end-diastolic velocity (Vd), and pulsatile index. Twenty-six patients with VBD were enrolled, of which 15 had IS and 11 did not. The incidence of classical vascular risk factors, including age, sex, hypertension, diabetes, and hypercholesterolemia, did not differ significantly between the two groups. The BA diameters of the stroke group were significantly higher than that of the nonstroke group (6.57 ± 1.00 mm vs. 5.06 ± 0.50 mm, p = 0.000). The height of the BA bifurcation in the stroke and nonstroke groups was statistically significant (p = 0.002). Compared with the nonstroke group, the Vm, Vs, and Vd of the BA in the stroke group were lower, but the difference was not significant. In the 16 patients with atherosclerotic stenosis, 30 atherosclerotic plaques were found in the BA, 18 (60%) in the greater curvature, and 12 (40%) in the lesser curvature. In addition, one artery dissection (on the lesser curvature) and two dissecting aneurysms (on the greater curvature) were found in the BA of three patients, respectively. The BA diameter and bifurcation height are factors related to IS in patients with VBD. The mechanism of stroke in patients with VBD may involve abnormal hemodynamics, artery dissection, and atherosclerosis. HR-MRI is a useful method for evaluating the risk and underlying mechanism of stroke in patients with VBD.

Mapping Chinese annual gross primary productivity with eddy covariance measurements and machine learning.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr-1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes.