Dynamics of Nanosecond Laser Pulse Propagation and of Associated Instabilities in a Magnetized Underdense Plasma.

The propagation and energy coupling of intense laser beams in plasmas are critical issues in inertial confinement fusion. Applying magnetic fields to such a setup has been shown to enhance fuel confinement and heating. Here we report on experimental measurements demonstrating improved transmission and increased smoothing of a high-power laser beam propagating in a magnetized underdense plasma. We also measure enhanced backscattering, which our kinetic simulations show is due to magnetic confinement of hot electrons, thus leading to reduced target preheating.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study].

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

[Research progress in clinical application of three-dimensional reconstruction in orbital measurement].

The structure of orbit is complex and its function is critical. Quantitative determination of orbital volume is valuable to diagnosis and treatment of orbital diseases, but a standardized and reproducible orbital volume measurement method is still not available. Recently, with the development of three-dimensional reconstruction, many researchers gradually convert their insight into three-dimensional orbital measurement. This paper reviews the common methods of three-dimensional orbital measurement used by investigators, including some innovative ideas, and their clinical applications in order to make a comprehensive overview of the current orbital measurement technology, explore the possible improvement direction, and better serve the clinical.

RADIOMICS BASED ON TWO-DIMENSIONAL AND THREE-DIMENSIONAL ULTRASOUND FOR EXTRATHYROIDAL EXTENSION FEATURE PREDICTION IN PAPILLARY THYROID CARCINOMA.

Aim: To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and three-dimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods: 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results: The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion: Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.

[Preliminary study of the changes in blood system in pyrrolizidine alkaloid-related liver damage].

Objective: To preliminary explore the changes in blood system in pyrrolizidine alkaloids (PAs)-related liver damage. Methods: General situation, liver function, biochemical blood test, routine blood test, coagulation function markers, etc., of 77 cases with drug-induced liver damage admitted to the Zhongshan Hospital Affiliated to Fudan University from 2012 to 2019 were retrospectively analyzed. Patients' were divided into PA group, other traditional Chinese medicine group and Western medicine group according to their medication history. Simultaneously, the changes in liver function were observed in the established mice model of monocrotaline-induced liver damage. Liver tissues HE staining and blood routine indexes were observed. Results: 24 cases received PA, 24 cases received other traditional Chinese medicine, and 29 cases received western medicine. Alanine aminotransferase was lower in PA group than the other two groups (P < 0.05), and the total bilirubin and direct bilirubin were significantly lower than the other traditional Chinese medicine group (P < 0.05). The peripheral platelet count of the PA group was (84.11 ± 26.91) ×10(9)/L, which was significantly lower than the lower limit of normal, and had statistically significant difference with other traditional Chinese medicine and western medicine group (P < 0.01). Thrombocytocrit, mean platelet volume and platelet indices of PA group were statistically different from the other two groups (P < 0.05). The D-dimer level in patients with PA group was (2.62 ± 1.93) mg/L, which was higher than the upper limit of normal, and significantly higher than the D-dimer level of the other two groups of patients (P < 0.01). Meanwhile, prothrombin time was longer in PA group than that of the other two groups (P < 0.01), and platelets count were decreased significantly in the mouse model of monocrotaline-induced liver damage after alanine aminotransferase and aspartate aminotransferase elevation (P < 0.01). Conclusion: PA-related liver damage has lower peripheral platelet counts, and the peripheral platelet counts of these patients are lower than other types of drug-induced liver damage. In addition, increased D-dimer in patients with PA-related liver damage indicate a potential risk of thrombosis.

Laser-Produced Magnetic-Rayleigh-Taylor Unstable Plasma Slabs in a 20 T Magnetic Field.

Magnetized laser-produced plasmas are central to many novel laboratory astrophysics and inertial confinement fusion studies, as well as in industrial applications. Here we provide the first complete description of the three-dimensional dynamics of a laser-driven plasma plume expanding in a 20 T transverse magnetic field. The plasma is collimated by the magnetic field into a slender, rapidly elongating slab, whose plasma-vacuum interface is unstable to the growth of the "classical," fluidlike magnetized Rayleigh-Taylor instability.

Subchronic toxicity and genotoxicity studies of Antrodia mushroom ß-glucan preparation.

Antrodia cinnamomea is one of the most highly valued mushrooms utilized in traditional Taiwanese therapeutic practices. Its neutral monosaccharides (mannose, glucose and xylose) linked by a ß-D-glucan chain have been claimed to be responsible for its health benefits. The objective of the present study was to investigate adverse effects, if any, of ß-glucan (∼65% pure) from A. cinnamomea in subchronic toxicity and mutagenicity studies. In the subchronic toxicity study, Sprague Dawley rats (12/sex/group) were followed Organization for Economic Cooperation and Development (OECD) test guideline with Good Laboratory Practice (GLP) application, and were administered (gavage) Antrodia mushroom ß-glucan preparation at dose levels of 0, 500, 1000 and 2000 mg/kg body weight (bw)/day for 90 days. Treatment with ß-glucan preparation did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. The clinical pathology as studied by hematology, serum chemistry, urinalysis or terminal necropsy (gross or histopathology findings) did not reveal any treatment-related adverse effects. The results of mutagenicity studies as evaluated by gene mutations in Salmonella typhimurium, in vitro chromosome aberrations and in vivo micronucleus test in mice did not reveal any genotoxicity of ß-glucan preparation. Based on the subchronic study, the no observed-adverse-effect level (NOAEL) for ß-glucan preparation from Antrodia mushroom was determined as 2000 mg/kg bw/day, the highest dose tested.

[Assessment of renal function with intravoxel incoherent motion and diffusion tensor imaging in type 2 diabetic patients].

Objective: To evaluate the application value of intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) in detecting early-stage diabetic nephropathy and to assess the damage of ralated renal function. Methods: A total of 52 patients with type 2 diabetes diagnosed in Zhongda Hospital were collected from April 2016 to May 2017 and were assigned to DM group (diabetes without nephropathy, n=32) and DN group (diabetes with nephropathy, n=20) according to detection of microalbuminuria, a cohort of healthy recipients were included as control group (n=27) in the meantime. All of the subjects underwent IVIM and DTI examination. The cortical and medullary parameters[IVIM: perfusion fraction f, tissue diffusivity D, pseudodiffuvisity D(*;) DTI: fractional anisotropy FA, apparent diffusion coefficient ADC, principal diffusivities (λ1, λ2, λ3)]were obtained respectively and were compared among groups. The relationship between MRI related parameters and estimated glomerular filtration rate (eGFR) were statistically investigated; and diagnostic performance of IVIM and DTI in discriminating DM and DN group was evaluated by receiver operating characteristic analysis. Results: The cortical and medullary f, D values in DN group were lower than those in DM group and control group (F=17.32, 15.69, 6.71, 10.94, all P<0.05). D values of all subjects showed positive correlations with eGFR (cortex r=0.518, medulla r=0.538, both P<0.05). The diagnostic efficiency of cortical f values to discriminate diabetes and diabetic nephropathy was 0.817, the cut-off value was 0.205. The medullary FA value in DM group was lower than that in control group ((0.371±0.051 vs 0.423±0.043, t=4.188, P<0.05); and the medullary FA value in DN group (0.315±0.062) was lower than that in control and DM group (F=25.08, P<0.05). The medullary λ3 values in DM group and DN group were all significantly higher than that in control group (F=7.86, P<0.05). The diagnostic efficiency of medullary FA values to discriminate diabetes and diabetic nephropathy was 0.763, the cut-off value was 0.344. Conclusion: IVIM and DTI can reflect the abnormal perfusion and diffusion during early-stage diabetic nephropathy and have the potential value to assess the damage of ralated renal function.

Enhancement of Quasistationary Shocks and Heating via Temporal Staging in a Magnetized Laser-Plasma Jet.

We investigate the formation of a laser-produced magnetized jet under conditions of a varying mass ejection rate and a varying divergence of the ejected plasma flow. This is done by irradiating a solid target placed in a 20 T magnetic field with, first, a collinear precursor laser pulse (10^{12} W/cm^{2}) and, then, a main pulse (10^{13} W/cm^{2}) arriving 9-19 ns later. Varying the time delay between the two pulses is found to control the divergence of the expanding plasma, which is shown to increase the strength of and heating in the conical shock that is responsible for jet collimation. These results show that plasma collimation due to shocks against a strong magnetic field can lead to stable, astrophysically relevant jets that are sustained over time scales 100 times the laser pulse duration (i.e., >70 ns), even in the case of strong variability at the source.

[Clinical analysis in a cohort of 102 patients with myelodysplastic syndrome characterized by erythroid hyperplasia].

Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University. Clinical characteristics, karyotype, and the prognostic significance of erythroid hyperplasia were evaluated. Results: A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities. The most frequently involved chromosomes were chromosome 8 (39.5% of all abnormal karyotypes), chromosome 7 (22.9%), followed by chromosome 5 (18.8%), chromosome 1 (16.7%) and chromosome 20 (16.7%). Hemoglobin (Hb) level affected the prognosis by survival analysis. The overall survival (OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L (P<0.001). Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001). The extent of erythroid hyperplasia in bone marrow did not impact on prognosis (P=0.187). Conclusions: Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia, more common erythroid dyshematopoiesis, more frequent 8 and 1 chromosome abnormalities. The degree of erythroid hyperplasia is not correlated with prognosis. Allogeneic hematopoietic stem cell transplantation improves the prognosis.

Fitness and Competitive Ability of Botrytis cinerea Isolates with Resistance to Multiple Chemical Classes of Fungicides.

Resistance to multiple chemical classes of fungicides in Botrytis cinerea isolates from eastern United States strawberry fields is common and strategies to control them are needed. In this study, we compared fitness and competitive ability of eight sensitive isolates (S), eight isolates resistant to five or six chemical classes of fungicides but not to phenylpyrroles (5CCR), and eight isolates resistant to six or seven chemical classes including phenylpyrroles (6CCR/MDR1h). The latter included the MDR1h phenotype due to overexpression of atrB based on Δ497V/L in mrr1. The 6CCR/MDR1h isolates grew more slowly at 4°C on potato dextrose agar, and both 5CCR and 6CCR/MDR1h isolates were hypersensitive to osmotic stress compared with S isolates. In contrast, no differences were found in oxidative sensitivity, aggressiveness, and spore production in vivo, and sclerotia production and viability in vitro. In competition experiments, the 5CCR and 6CCR/MDR1h isolates were both outcompeted by S isolates and 6CCR/MDR1h isolates were outcompeted by 5CCR isolates in the absence of fungicide pressure. Under selective pressure of a fludioxonil/pyraclostrobin rotation, the 6CCR/MDR1h isolates dominated after coinoculation with 5CCR and S isolates. The competitive disadvantage of 5CCR and especially 6CCR/MDR1h isolates suggest that, in the absence of fungicide selection pressure, S isolates may reduce inoculum potential of multifungicide-resistant isolates under field conditions.

Sensitivity of Colletotrichum Species, Including C. fioriniae and C. nymphaeae, from Peach to Demethylation Inhibitor Fungicides.

Few fungicides are effective against anthracnose, caused by Colletotrichum spp., and emerging resistance makes the search for chemical alternatives more relevant. Isolates of the Colletotrichum acutatum species complex were collected from South Carolina and Georgia peach orchards and phylogenetic analysis of the combined internal transcribed spacer region, glyceraldehyde-3-phosphate dehydrogenase, and ß-tubulin gene sequences separated the isolates into C. nymphaeae and C. fioriniae. The sensitivity of these and three other previously reported Colletotrichum spp. from peach, including C. fructicola, C. siamense, and C. truncatum, to demethylation inhibitor (DMI) fungicides difenoconazole, propiconazole, tebuconazole, metconazole, flutriafol, and fenbuconazole was determined based upon mycelial growth inhibition. C. truncatum was resistant to tebuconazole, metconazole, flutriafol, and fenbuconazole and C. nymphaeae was resistant to flutriafol and fenbuconazole based on 50% effective concentration (EC50) values >100 µg/ml. C. fructicola and C. siamense were sensitive to all DMI fungicides (EC50 values of 0.2 to 13.1 µg/ml). C. fioriniae subgroup 2 isolates were less sensitive to DMI fungicides (EC50 values of 0.5 to 16.2 µg/ml) compared with C. fioriniae subgroup 1 (EC50 values of 0.03 to 2.1 µg/ml). Difenoconazole and propiconazole provided the best control efficacy in vitro to all five species, with EC50 values of 0.2 to 2.7 µg/ml. Tebuconazole and metconazole were effective against all Colletotrichum spp., except for C. truncatum. The strong in vitro activity of some DMI fungicides against Colletotrichum spp. may be exploited for improved anthracnose disease management of peach.

Topology of megagauss magnetic fields and of heat-carrying electrons produced in a high-power laser-solid interaction.

The intricate spatial and energy distribution of magnetic fields, self-generated during high power laser irradiation (at Iλ^{2}∼10^{13}-10^{14} W.cm^{-2}.µm^{2}) of a solid target, and of the heat-carrying electron currents, is studied in inertial confinement fusion (ICF) relevant conditions. This is done by comparing proton radiography measurements of the fields to an improved magnetohydrodynamic description that fully takes into account the nonlocality of the heat transport. We show that, in these conditions, magnetic fields are rapidly advected radially along the target surface and compressed over long time scales into the dense parts of the target. As a consequence, the electrons are weakly magnetized in most parts of the plasma flow, and we observe a reemergence of nonlocality which is a crucial effect for a correct description of the energetics of ICF experiments.

Sensitivity of Monilinia fructicola from Peach Farms in China to Four Fungicides and Characterization of Isolates Resistant to Carbendazim and Azoxystrobin.

Brown rot of peach caused by Monilinia fructicola can cause considerable preharvest and postharvest losses in China. Fungicides are increasingly utilized to minimize such losses. Eighty isolates of M. fructicola were collected from commercial peach orchards located in five provinces in China and the sensitivity to carbendazim, azoxystrobin, tebuconazole, and boscalid was determined. Resistance to carbendazim was detected only in the Yunnan province in 15 of 16 isolates. Characterization of carbendazim-resistant isolates revealed stable resistance, no fitness penalty, and negative cross resistance to diethofencarb. Resistant isolates produced disease symptoms on detached fruit sprayed with label rates of formulated carbendazim and possessed the amino acid mutation E198A in ß-tubulin. Resistance to azoxystrobin was detected in 3 of 10 isolates from Fujian. In contrast to carbendazim resistance, however, azoxystrobin resistance was unstable, associated with a fitness penalty, and not associated with mutations in the target gene cytochrome b. The concentration at which mycelial growth is inhibited 50% (EC50) values of the azoxystrobin-sensitive isolates were 0.02 to 1.94 µg/ml, with a mean value of 0.54 µg/ml. All isolates were sensitive to tebuconazole, with a mean EC50 value of 0.03 µg/ml. The EC50 values for boscalid were 0.01 to 3.85 µg/ml, with a mean value of 1.02 µg/ml. Our results indicate that methyl benzimidazole carbamates (MBCs), quionon outside inhibitors, demethylation inhibitor fungicides, and succinate dehydrogenase inhibitors are likely to be very effective in controlling brown rot in many peach production areas in China, but that resistance to MBCs is emerging.

First Report of Brown Rot of Apricot Caused by Monilia mumecola.

In May 2013, apricot (Prunus armeniaca) fruits covered with grayish, conidial masses were collected from an unknown cultivar in an experimental field of Huazhong Agricultural University, Wuhan, Hubei Province. About 3 to 5% of fruit was infected and affected apricots had tan to white zones of sporulation, which resembled brown rot caused by Monilia species. Conidia were harvested from the surface of the sporulating apricot fruit and spread onto shallow potato dextrose agar (PDA) media (about 2 mm in thickness) using sterile cotton swabs. Conidia were lemon-shaped and mean size was 15.7 (10 to 22.5) × 25 (16.25 to 35) µm. Conidia on PDA were incubated at 23°C for 3 h in darkness, then observed under microscope. More than two germ tubes were produced from each conidium, which was the distinctive trait of Monilia mumecola species (2). Single-spore isolates were obtained and 3 isolates were cultured on PDA in petri dishes. Mycelium grew at an average of 15 mm per day, and the colony showed concentric rings of mycelium with lobbed margins at 23°C in darkness. A 712-bp fragment was PCR amplified from ß-tubulin gene (TUB2) of all the nine isolates investigated indicative of M. mumecola (2). The ribosomal ITS1-5.8S-ITS2 regions of nine isolates were also PCR-amplified from genomic DNA using primers ITS1 and ITS4 and then sequenced (4). ITS sequences were identical to ITS sequences of M. mumecola from China (HQ908786) and Japan (AB125613, AB125614, and AB125620), but only has 98% and 97% identity with the closest species M. laxa (EU042149) and M. fructicola (HQ908789) according to BLAST search in GenBank. Pathogenicity was confirmed by inoculating mycelial plugs of three isolates into six surface-sterilized apricots wounded with a 6-mm diameter sterile cork borer. Control fruit received plain PDA plugs and was incubated in a moist chamber at 23°C with 12 h light/12 h dark. All inoculated fruit developed typical brown rot symptoms with sporulating areas as described above after 3 days of incubation, while control fruits remained healthy. The developing spores on inoculated fruit were re-isolated and confirmed to be M. mumecola. M. mumecola was first isolated from Prunus mume in Japan in 1982 as an unknown Monilia species (3), then identified and the nomenclature was provided in 2004 (1). To our knowledge, this is the first report of M. mumecola on P. armeniaca indicating that M. mumecola has spread to different hosts. References: (1) Y. Harada et al. J. Gen. Plant Pathol. 70:297, 2004. (2) M. J. Hu et al. Plos One, 6(9):e24990, 2011. (3) S. Nakao. Kongetsu-no-noyaku, 1:92, 1992. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

First Report of Brown Rot Caused by Monilia mumecola on Chinese Sour Cherry in Chongqing Municipality, China.

Cherry is widely planted in China, from Liaoning, Beijing, Hebei, Shandong, Zhejiang, Jiangsu, and Anhui provinces (eastern China), to Shaanxi, Sichuan, Chongqing, and Guizhou provinces (western China). The brown rot fungus Monilinia fructigena causes considerable production losses in cherry production in Liaoning Province (3). In May 2013, Chinese sour cherry (Prunus pseudocerasus) cv. Wupi displaying symptoms of brown rot was found in an orchard in Chongqing municipality. Diseased cherry fruit had a brown rot sporulating with grayish, conidial tufts. The fruit later succumbed to the soft rot or shivered and became a mummy. Single-spore isolations on PDA resulted in colonies with concentric rings of pigmented mycelium with lobbed margins. Conidia were broadly ellipsoid to subglobose, occasionally even globose, with an average size of 16 × 12.7 µm. Multiple germ tubes were produced from each conidium, a germination pattern unique to Monilia mumecola (1,2,4). The pathogen identity was confirmed by multiplex PCR as described by Hu et al. (2). The PCR resulted in a 712-bp amplicon, which is diagnostic of M. mumecola. Further sequencing of the internal transcribed spacer (ITS) region 1 and 2 and 5.8S gene further indicated 100% identity with that of M. mumecola isolates from China (Accession No. HQ908786) and from Japan (AB125613, AB125614, and AB125620). Koch's postulates were confirmed by inoculating mature cherry fruit with mycelia plugs. Inoculated fruit were placed in a sterilized moist chamber, and incubated at 22°C with 12 h light/dark cycle. Inoculated fruit developed typical brown rot symptoms only 2 days after inoculation, while the control fruit, inoculated with a sterile PDA plug, remained healthy. The pathogen isolated from inoculated symptomatic fruit was confirmed to be M. mumecola based on morphological characteristics and germination pattern. It should be noted that the conidia on inoculated fruit showed an average size of 20 × 15.3 µm, significantly bigger than that of from PDA, and most produced more than three germ tubes. The inoculation experiments were performed in triplicates. M. mumecola was first reported as the causal agent of brown rot of mume in Japan in 2004 (1). Later studies demonstrated that it is also pathogen on other stone fruits, e.g., peach, nectarine (2), and apricot (4). To our knowledge, this is the first report of cherry brown fruit rot caused by M. mumecola, and the first report of M. mumecola in Chongqing municipality. References: (1) Y. Harada et al. J. Gen. Plant Pathol. 70:297, 2004. (2) M. J. Hu et al. Plos One 6(9): e24990, 2011. (3) Z. H. Liu et al. J. Fruit Sci. 29:423, 2012. (4) L. F. Yin et al. Plant Dis. 98:694, 2014.

[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.