Retraction Note: Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia-reperfusion brain injury in rats.

The article "Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia-reperfusion brain injury in rats", by L.-J. Jiang, S.-M. Zhang, C.-W. Li, J.-Y. Tang, F.-Y. Che, Y.-C. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1532-1540-PMID: 28429353 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/4C502B6EB4FCA59AC9F42A8278A3D4), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive and have not provided the study's raw data. The journal investigation revealed several figure duplications and manipulations in Figures 3 and 6. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12521.

[Regional differences of chronic rhinosinusitis endotypes based on tissue inflammatory and remodeling biomarkers].

Objective: To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison. Methods: The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis. Results: Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 (n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 (n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 (n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 (n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion: CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

[Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection].

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

[Clinical characteristics of 11 patients with chronic lymphocytic leukemia with t (14;19) (q32;q13)].

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.

[Clinical efficacy and safety analysis of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer].

Objective: To investigate the clinical efficacy and safety of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer. Methods: Clinical data of 36 patients who underwent CT-guided 125I seed implantation for mediastinal lymph node metastasis of lung cancer from August 2013 to April 2020 in three hospitals of the Northern radioactive particle implantation treatment collaboration group were retrospectively collected, including 24 males and 12 females, aged 46 to 84 years. Cox regression model was used to analyze the relationship between local control rate, survival rate and tumor stage, pathological type, postoperative D90, postoperative D100 and other variables, and to analyze the occurrence of complications. Results: The objective response rate of CT-guided 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer was 75% (27/36), the median control time was 12 months, the 1-year local control rate was 47.2% (17/36), and the median survival time was 17 months. The 1-year and 2-year survival rates were 61.1% (22/36) and 22.2% (8/36) respectively. Univariate analysis showed that in the treatment of mediastinal lymph node metastasis with CT-guided 125I implantation, factors related to local control included tumor stage (HR=5.246, 95%CI: 2.243-12.268, P<0.001), postoperative D90 (HR=0.191, 95%CI: 0.085-0.431, P<0.001), postoperative D100 (HR=0.240, 95%CI: 0.108-0.533, P<0.001); The factors affecting survival were tumor stage (HR=2.712, 95%CI: 1.356-5.425, P=0.005), postoperative D90 (HR=0.110, 95%CI: 0.041-0.294, P<0.001), postoperative D100 (HR=0.212, 95%CI: 0.092-0.489, P<0.001). Multivariate analysis showed that tumor stage (HR=5.305, 95%CI: 2.187-12.872, P<0.001) and postoperative D100 (HR=0.237, 95%CI: 0.099-0.568, P<0.001) were correlated with local control rate. Tumor stage (HR=2.347, 95%CI: 1.095-5.032, P=0.028) and postoperative D90 (HR=0.144, 95%CI: 0.051-0.410, P<0.001) were correlated with survival. In terms of complications, 9 of the 36 patients had pneumothorax, and 1 of them was cured by closed thoracic drainage for severe pneumothorax; 5 cases developed pulmonary hemorrhage and 5 cases developed hemoptysis, which recovered after hemostasis treatment. One case developed pulmonary infection and recovered after anti-inflammatory treatment. No radiation esophagitis and radiation pneumonia occurred; No grade 3 or higher complications occurred. Conclusion: 125I seed implantation in the treatment of lung cancer mediastinal lymph node metastasis has a high local control rate and controllable adverse effects.

Withdrawn as duplicate: Post-yield softening of bending-dominated metal metamaterials.

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI https://doi.org/10.1210/pnasnexus/pgad075.

Post-yield softening of bending-dominated metal metamaterials.

Post-yield softening (PYS) plays an important role in guiding the design of high-performance energy-absorbing lattice materials. PYS is usually restricted to lattice materials that are stretching dominated according to the Gibson-Ashby model. Contrary to this long-held assumption, this work shows that PYS can also occur in various bending-dominated Ti-6Al-4V lattices with increasing relative density. The underlying mechanism for this unusual property is elucidated using the Timoshenko beam theory. It is attributed to the increase in stretching and shear deformation with increasing relative density, thereby increasing the tendency towards PYS. The finding of this work extends perspectives on PYS for the design of high-performance energy-absorbing lattice materials.

Multi-extreme conditions at the Second Target Station.

Three concepts for the application of multi-extreme conditions under in situ neutron scattering are described here. The first concept is a neutron diamond anvil cell made from a non-magnetic alloy. It is shrunk in size to fit existing magnets and future magnet designs and is designed for best pressure stability upon cooling. This will allow for maximum pressures above 10 GPa to be applied simultaneously with (steady-state) high magnetic field and (ultra-)low temperature. Additionally, an implementation of miniature coils for neutron diamond cells is presented for pulsed-field applications. The second concept presents a set-up for laser-heating a neutron diamond cell using a defocused CO2 laser. Cell, anvil, and gasket stability will be achieved through stroboscopic measurements and maximum temperatures of 1500 K are anticipated at pressures to the megabar. The third concept presents a hybrid levitator to enable measurements of solids and liquids at temperatures in excess of 4000 K. This will be accomplished by a combination of bulk induction and surface laser heating and hyperbaric conditions to reduce evaporation rates. The potential for deployment of these multi-extreme environments within this first instrument suite of the Second Target Station is described with a special focus on VERDI, PIONEER, CENTAUR, and CHESS. Furthermore, considerations for deployment on future instruments, such as the one proposed as TITAN, are discussed. Overall, the development of these multi-extremes at the Second Target Station, but also beyond, will be highly advantageous for future experimentation and will give access to parameter space previously not possible for neutron scattering.

[Large B-cell lymphoma with IRF4 rearrangement: six case reports and a literature review].

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity (n=five cases) and no starry sky pattern (n=6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

[Risk factors for leukemia transformation in patients with myelodysplastic syndromes].

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

[The immunoregulatory functions of exosome derived from mesenchymal stem cells that are genetically modified by adeno-associated virus].

Objectives: To verify the effects and mechanisms of natural MSC-exosome in treating acute GVHD in mice, explore and establish a method for targeted modification of MSC-exosome, and verify the functions of the modified MSC-exosome. Methods: In different doses of MSC-exosome groups and MSC group, weight loss in acute GVHD mice was observed; then the proliferation levels of activated T cells were measured through T cell activation experiment in vitro and OVA antigen-specific T cell activation experiment in vivo. AAV2YF3 mutants carrying PD-L1 and PD-L1-ITGB1 were obtained after the construction of recombinant expression vectors and were then applied to infect human MSC to modify their exosome. The immunoregulatory functions of the modified MSC-exosome were measured with the abovementioned methods. Results: ①Mouse MSC-exosome (300 µg×3 times) and MSC (1×10(6)×3 times) effectively alleviated the weight loss in acute GVHD mice. ②Compared with IL-2, 10, 25 and 50 µg human MSC-exosome inhibited the proliferation of activated T cells in vitro, respectively, 86.0% (IL-2) , 40.0%, 39.6%, and 42.8%; compared with PBS, 50, 100 and 200 µg mouse MSC-exosome inhibited the proliferation of antigen-specific activated OT-1 cells in vivo, respectively, 42.6%, 33.1%, 14.2%, and 10.6%. ③After the infection of AAV2YF3 mutant carrying PD-L1 or PD-L1-ITGB1, the positive proportion of MSC-exosome exceeds 40% and 60%, respectively. ④Compared with the natural state, MSC-exosome modified by PD-L1 or PD-L1-ITGB1 showed better proliferation inhibitory effect in vivo and increased the proportion of Treg cells in vitro. Conclusions: MSC-exosome exhibited similar immunomodulatory effects with MSC. MSC-exosome after PD-L1 and PD-L1-ITGB1-targeted modification effectively inhibited the proliferation of activated T cells and increased the proportion of Treg cells.

Investigating the Potential Mechanism of Pydiflumetofen Resistance in Sclerotinia sclerotiorum.

The necrotrophic pathogen Sclerotinia sclerotiorum is one of the most damaging and economically important plant pathogens. Pydiflumetofen, which was developed by Syngenta Crop Protection, has already been registered in China for the management of Sclerotinia stem rot, which was caused by S. sclerotiorum in oilseed rape. In an attempt to preempt and forestall the development of resistance to this useful fungicide, the current study was initiated to investigate the potential mechanism of resistance in laboratory mutants. Five pydiflumetofen-resistant S. sclerotiorum mutants were successfully generated by repeated exposure to the fungicide under laboratory conditions. Although the mutants had greatly reduced sensitivity to pydiflumetofen, they were also found to have significantly (P < 0.05) reduced fitness, exhibiting reduced mycelial growth and sclerotia formation on potato dextrose agar medium. However, three of the four mutants had significantly (P < 0.05) increased pathogenicity on detached soybean leaves compared with their respective parental isolates, indicating a moderate to high level of fungicide resistance risk according to the criteria of the Fungicide Resistance Action Committee. Sequence analysis of four succinate dehydrogenase (Sdh) target genes identified several nucleotide changes in the sequences of the pydiflumetofen-resistant mutants, most of which were synonymous and caused no changes to the predicted amino acid sequences. However, all of the pydiflumetofen-resistant mutants had two amino acid point mutations (A11V and V162A) in their predicted SsSdhB sequence. No similar changes were found in the SsSdhA, SsSdhC, and SsSdhD genes of any of the mutants tested. In addition, there was a positive cross-resistance between pydiflumetofen and boscalid, and no cross-resistance between pydiflumetofen and other commonly used fungicides, including tebuconazole, fludioxonil, cyprodinil, dimethachlone, prochloraz, pyraclostrobin, fluazinam, procymidone, and carbendazim. These results indicate that pydiflumetofen has great potential as an alternative fungicide for the control of S. sclerotiorum, especially where resistance to other fungicides has already emerged. Mixing or alternate application with fludioxonil, prochloraz, and fluazinam could be used to limit the risk of resistance to pydiflumetofen.

[Evaluation of intravascular therapy for cerebral ischemic tandem stenosis].

Objective: To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis. Methods: Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores. Results: Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients'mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2. Conclusion: Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

[Evaluation of the single stage treatment of intracranial or extracranial artery stenosis combined with intracranial aneurysm:experience from a single center].

Objective: To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm. Methods: The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded. Results: Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke. Conclusions: For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.

Exploring the Biological and Molecular Characteristics of Resistance to Fludioxonil in Sclerotinia sclerotiorum From Soybean in China.

Sclerotinia sclerotiorum is one of the most damaging and economically important necrotrophic plant pathogens, infecting more than 400 plant species globally. Although the phenylpyrrole fungicide fludioxonil has high activity against S. sclerotiorum, reports indicate that there is also substantial potential for the development of fungicide resistance. However, the current study investigating five fludioxonil-resistant laboratory mutants found a significant fitness cost associated with fludioxonil resistance resulting in significantly (P < 0.05) reduced mycelial growth and sclerotia formation on potato dextrose agar as well as significantly (P < 0.05) lower pathogenicity on detached tomato leaves, with one mutant, LK-1R, completely losing the capacity to cause infection. In addition, all of the fludioxonil-resistant mutants had significantly (P < 0.05) increased sensitivity to osmotic stress (0.5 M of potassium chloride and 1.0 M of glucose), which is consistent with the proposed fludioxonil target sites within the high osmolarity glycerol stress response mitogen-activated protein kinase (HOG1-MAPK) signaling transduction pathway. Sequence analysis of six genes from this two-component pathway, including SsHk, SsYpd, SsSk1, SsSk2, SsPbs, and SsHog, revealed several mutations that may be associated with fludioxonil resistance. For example, six separate point mutations were found in SsHk that led to changes in the predicted amino acid sequence, including A136G, F249V, G353A, E560K, M610K, and K727R. Similarly, SsPbs had three mutations (D34G, S46L, and L337E), SsSk1 and SsYpd had two (S53G and A795V for SsSk1, and E67G and Y141H for SsYpd), and SsHog and SsSk2 had one each (V220A and S763P, respectively). To our knowledge, these constitute the first reports of amino acid changes in proteins of the HOG1-MAPK pathway being associated with fludioxonil resistance in S. sclerotiorum. This study also showed a positive cross-resistance between fludioxonil and dimethachlone and procymidone, but none with tebuconazole or carbendazim, indicating that the inclusion of tebuconazole within an integrated pest management program could reduce the risk of fludioxonil resistance developing in field populations of S. sclerotiorum and ensure the sustainable production of soybeans in China into the future.