First report of leaf spot on pecan caused by Choanephora cucurbitarum in China.

Pecan (Carya illinoinensis K. Koch) is an important and widely planted nut tree species in Jiangsu Province, China (Mo et al. 2018). In July 2020, leaf spot symptoms were frequently observed on pecan in Jurong, Jiangsu Province (119°15'36"E, 32°1'6"N). Disease incidences ranged from 40 to 65% among 150 mature pecan trees from three nurseries. The disease severity index (DSI, Jiang et al. 2019) reached 58.4. Symptoms began as small brown spots scattered on leaves that gradually expanded to large, circular to irregular black and brown necrotic lesions. In severe cases, lesions developed on large portions of a single leaf, and eventually the dead leaves fell from the trees. Three monoconidial isolates (Chen2346, Chen2347, Chen2348) were isolated from lesion margins and cultured on potato dextrose agar (PDA) medium. Colonies on PDA were white and cottony, later becoming light gray with abundant reproductive structures. Sporangiophores were aseptate, hyaline, unbranched, and apically dilated to form a clavate vesicle, which produced sporangia. Sporangia were globular to ellipsoid, brown to dark brown, 103 to 128 µm in length, and 88 to 114 µm in width (n = 30). Sporangiola were brown, ellipsoid to ovoid, with longitudinal striae, and measured 13.9 to 18.8 × 7.9 to 10.8 µm (n = 60). The morphological characteristics of these isolates agreed with descriptions of Choanephora cucurbitarum (Kirk 1984). Genomic DNA of these three monoconidial isolates was extracted, and the partial sequences of the internal transcribed spacer (ITS) and large subunit (LSU) of rDNA were amplified using primer pairs ITS1/ITS4 (White et al. 1990) and LR0R/LR7 (Vilgalys and Hester 1990), respectively. The consensus sequences (GenBank accession nos.: OP315248 to OP315250 for ITS and OP315251 to OP315253 for LSU) were aligned using BLASTn and showed100% identity with the sequences from C. cucurbitarum found in GenBank (accession nos.: MF942131 for ITS and ON025788 for LSU). To further confirm the identity, a phylogenetic analysis was performed with MEGA (v.7.0) and MrBayes (v.3.1.2) software, using the maximum likelihood and Bayesian inference methods, respectively. The multigene phylogeny revealed that the three isolates in this study, as well as, C. cucurbitarum specimen, clustered as a strongly supported monophyletic group (99 bootstrap value; 0.95 posterior probabilities). Based on the morphological and molecular data, the isolates were identified as C. cucurbitarum. To confirm pathogenicity, healthy pecan seedlings (2 years old) were each inoculated with a mycelial block (3 × 3 mm) excised from the margin of a colony on the vein of each leaf. Seedlings treated with non-colonized PDA blocks were used as controls. The inoculated seedlings were maintained in sterile plastic boxes with moistened sheets of filter paper at 25 ± 1°C and a 12-h photoperiod. Fifteen leaves per isolate were tested for each treatment. The experiment was repeated twice. Three days after inoculation, symptoms similar to those in the field appeared, whereas the control leaves remained symptomless. Subsequently, C. cucurbitarum was reisolated from the lesions and morphologically identified, confirming Koch's postulates. To the best of our knowledge, this is the first report of C. cucurbitarum causing leaf spot on C. illinoinensis in China. This study provides the foundation to further investigate the biology, epidemiology, and management of this disease.

First report of leaf spot disease caused by Corynespora cassiicola on American sweetgum (Liquidambar styraciflua L.) in China.

American sweetgum (Liquidambar styraciflua L.) is a forest plant native to North America, which has been introduced into other countries due to its ornamental and medicinal values. In June 2019, symptoms of leaf spots on sweetgum were observed in a field (5 ha) located in Xuzhou, Jiangsu Province, China. On this field, approximately 45% of 1,000 trees showed the same symptoms. Symptoms were observed showing irregular or circular dark brown necrotic lesions approximately 5 to 15 mm in diameter with a yellowish margin on the leaves. To isolate the pathogen, diseased leaf sections (4×4mm) were excised from the margin of the lesion, surface-sterilized with 0.1% NaOCl for 90 s, rinsed 4 times in sterile distilled water, air dried and then transferred on potato dextrose agar (PDA) medium at 25°C in the dark. Pure cultures were obtained by monospore isolation after subculture. Ten purified isolates, named FXI to FXR, were transferred to fresh PDA and incubated as above to allow for morphological and molecular identification. After 7 days, the aerial mycelium was abundant, fluffy and exhibited white to greyish-green coloration. The conidia were dark brown or olive, solitary or produced in chains, obclavate, with 1 to 15 pseudosepta, and measured 45 to 200µm  10 to 18µm. Based on morphological features, these 10 isolates were identified as Corynespora cassiicola (Ellis et al. 1971). Genomic DNA of each isolate was extracted from mycelia using the cetyltrimethylammonium bromide (CTAB) method. The EF-1α gene and ITS region were amplified and sequenced with the primer pairs rDNA ITS primers (ITS4/ITS5) (White et al. 1990) and EF1-728F/EF-986R (Carbone et al.1999) respectively. The sequences were deposited in GenBank. BLAST analysis revealed that the ITS sequence had 99.66% similarity to C. cassiicola MH255527 and that the EF-1α sequence had 100% similarity to C. cassiicola KX429668A. maximum likelihood phylogenetic analysis based on EF-1α and ITS sequences using MEGA 7 revealed that ten isolates were placed in the same clade as C. cassiicola (Isolate: XQ3-1; accession numbers: MH572687 and MH569606, respectively) at 98% bootstrap support. Based on the morphological characteristics and phylogenetic analyses, all isolates were identified as C. cassiicola. For the pathogenicity test, a 10 µl conidial suspension (1×105 spores/ml) of each isolate was dripped onto healthy leaves of 2-year-old sweetgum potted seedlings respectively. Leaves inoculated with sterile water served as controls. Three plants (3 leaves per plant) were conducted for each treatment. The experiment was repeat twice. All seedlings were enclosed in plastic transparent incubators to maintain high relative humidity (90% to 100%) and incubated in a greenhouse at 25°C with a 12-h photoperiod. After 10 days, leaves inoculated with conidial suspension of each isolate showed symptoms of leaf spots, similar to those observed in the field. Control plants were remained healthy. In order to reisolate the pathogen, surface-sterilized and monosporic isolation was conducted as described above. The same fungus was reisolated from the lesions of symptomatic leaves, and its identity was confirmed by molecular and morphological approaches, thus fulfilling Koch's postulates. Chlorothalonil and Boscalid can be used to effectively control Corynespora leaf spot (Chairin T et al.2017). To our knowledge, this is the first report of leaf spot caused by C. cassiicola on L. styraciflua in China.

Dieback and Leaf Spot in Box Elder (Acer negundo) Caused by Exserohilum rostratum.

Leaf spot and dieback were observed on box elder (Acer negundo) grown in a nursery in Tai'an city, Shandong Province, China, in 2019, with a disease incidence of 86%. The incidences of Exserohilum rostratum isolation were 75% from the shoots and 66.6% from the leaves of field-infected plants. Isolates were identified at the species level on the basis of morphological characteristics and through phylogenetic analysis of concatenated partial sequences of the internal transcribed spacer (ITS) region and cam, gapdh, tef1, rpb2, tub2, and his genes from the Exserohilum isolates. The effects of temperature on the mycelial growth of the Exserohilum rostratum isolates were also characterized. In greenhouse tests, seedlings inoculated with the pathogen exhibited systemic symptoms similar to those observed in the field. In pathogenicity experiments on shoots, wounded seedlings were observed to be blighted, suggesting that leaf spot and dieback may develop into more severe blight or dieback when high winds, sudden temperature decreases, or insect infestations occur. To our knowledge, this is the first report of dieback and leaf spot caused by E. rostratum on a species of A. negundo.

First report of leaf spot disease caused by Stemphylium eturmiunum on American sweetgum (Liquidambar styraciflua L.) in China.

American sweetgum (Liquidambar styraciflua L.) is an important tree for landscaping and wood processing. In recent years, leaf spots on American sweetgum with disease incidence of about 53% were observed in about 1200 full grown plants in a field (about 8 ha) located in Pizhou, Jiangsu Province, China. Initially, dense reddish-brown spots appeared on both old and new leaves. Later, the spots expanded into dark brown lesions with yellow halos. Symptomatic leaf samples from different trees were collected and processed in the laboratory. For pathogen isolation, leaf sections (4×4mm) removed from the lesion margin were surface sterilized with 75% ethanol for 20s and then sterilized in 2% NaOCl for 30s, rinsed three times in sterile distilled water, incubated on potato dextrose agar (PDA) at 25 °C in the darkness. After 5 days of cultivation, the pure culture was obtained by single spore separation. 6 isolate samples from different leaves named FXA1 to FXA6 shared nearly identical morphological features. The isolate FXA1 (codes CFCC 54675) was deposited in the China Center for Type Culture Collection. On the PDA, the colonies were light yellow with dense mycelium, rough margin, and reverse brownish yellow. Conidiophores (23-35 × 6-10 µm) (n=60) were solitary, straight to flexuous. Conidia (19-34 × 10-21 µm) (n=60) were single, muriform, oblong, mid to deep brown, with 1 to 6 transverse septa. These morphological characteristics resemble Stemphylium eturmiunum (Simmons 2001). Genomic DNA was extracted from mycelium following the CTAB method. The ITS region, gapdh, and cmdA genes were amplified and sequenced with the primers ITS5/ITS4 (Woudenberg et al. 2017), gpd1/gpd2 (Berbee et al. 1999), and CALDF1/CALDR2 (Lawrence et al. 2013), respectively. A maximum likelihood phylogenetic analysis based on ITS, gapdh and cmdA (accession nos. MT898502-MT898507, MT902342-MT902347, MT902336-MT902341) sequences using MEGA 7.0 revealed that the isolates were placed in the same clade as S. eturmiunum with 98% bootstrap support. All seedlings for pathogenicity tests were enclosed in plastic transparent incubators to maintain high relative humidity (90%-100%) and incubated in a greenhouse at 25°C with a 12-h photoperiod. For pathogenicity, the conidial suspension (105 spores/ml) of each isolate was sprayed respectively onto healthy leaves of L. styraciflua potted seedlings (2-year-old, 3 replicate plants per isolate). As a control, 3 seedlings were sprayed with sterile distilled water. After 7 days, dense reddish-brown spots were observed on all inoculated leaves. In another set of tests, healthy plants (3 leaves per plant, 3 replicate plants per isolate) were wound-inoculated with mycelial plugs (4×4mm) and inoculated with sterile PDA plugs as a control. After 7 days, brown lesions with light yellow halo were observed on all inoculation sites with the mycelial plugs. Controls remained asymptomatic in the entire experiment. The pathogen was reisolated from symptomatic tissues and identified as S. eturmiunum but was not recovered from the control. The experiment was repeated twice with the similar results, fulfilling Koch's postulates. S. eturmiunum had been reported on tomato (Andersen et al. 2004), wheat (Poursafar et al. 2016), garlic (L. Fu et al. 2019) but not on woody plant leaves. To our knowledge, this is the first report of S. eturmiunum causing leaf spot on L. styraciflua in the world. This disease poses a potential threat to American sweetgum and wheat in Pizhou.

First Report of Wilt of European hornbeam (Carpinus betulus L.) Caused by Fusarium oxysporum in China.

European hornbeam (Carpinus betulus L.) has been used as an important ornamental species for urban landscaping since the Italian Renaissance (Rocchi et al. 2010). In May 2019, 15% of 3000 C. betulus trees with wilted leaves and root rot were observed in a field (about 26 ha) in Pizhou, Jiangsu Province, China. Internal discoloration of the stem began with brown to black discoloration of the vascular system and gradually spread to inward areas. Roots and stems from symptomatic plants were washed free of soil, surface sterilized with 0.8% NaOCl, rinsed three times in sterile H2O, and blotted dry with a paper towel. Small segments (0.5-cm-long) were cut from the discolored vascular tissues, and then put on potato dextrose agar (PDA) at 25°C in darkness. After 4 days, fungal colonies were observed on the PDA. Pure cultures were obtained by monosporic isolation, and 9 morphologically similar fungal isolates (EJ-1 to EJ-9) were obtained. All purified cultures were incubated on PDA at 25°C in darkness as the initial isolation. Colonies of the 9 isolates on PDA displayed entire margins and showed abundant pink aerial mycelia initially and turned to light violet with age. Microconidia were elliptical or oval in shape, 0 septate, (5.2-)8.7(-12.5) × (3.5-)3.6(-5.5) µm. Macroconidia were falciform, 0-4 septate, and straight to slightly curved with a notched foot cell, (17.1-)20.5(-28.4) × (3.8-)4.1(-4.6) µm. These morphological characteristics resemble Fusarium oxysporum (Leslie and Summerell 2006). Genomic DNA of each isolate was extracted from mycelia using a CTAB method (Mo¨ller et al. 1992). The RPB2, TEF1 and cmdA genes were amplified and sequenced with the primers 5f2/7c (Liu et al. 2000), EF-1Ha/EF-2Tb (Carbone and Kohn 1999) and Cal228F/CAL2Rd (Groenewald et al. 2013), respectively. The sequences were deposited in GenBank (Table 1). A maximum likelihood phylogenetic analysis based on RPB2, TEF1 and cmdA sequences using MEGA7 revealed that the isolates were placed in the F. oxysporum species complex with 98% bootstrap support. Based on the morphological and molecular characters, all 9 isolates were identified as F. oxysporum. A pathogenicity experiment was conducted using 30 2-year-old C. betulus seedlings potted in sterile peat, 27 for inoculation (3 replicate plants per isolate) and 3 for a negative control. The treated plants were planted in the peat mixed with 50 ml of a conidial suspension of each isolate respectively. The negative control was inoculated with sterilized water. Conidia were harvested from colonized plates of PDA using sterilized water and adjusted to a concentration of 1×107 conidia/ml. All 30 seedlings were incubated in a greenhouse at 25°C with a relative humidity of 80% and a 12-h photoperiod. The inoculated seedlings displayed wilt symptoms within 30 to 40 days, and eventually died within 75 to 85 days after inoculation. Control plants remained symptomless. F. oxysporum was successfully reisolated from the vascular tissues of symptomatic plants, and sequences of RPB2, TEF1 and cmdA of re-isolates matched those of the original isolates. No pathogen was isolated from the tissues of control plants. The experiment was repeat twice with the similar results, fulfilling Koch's postulates. F. oxysporum is an important soil-borne pathogen and can cause disease in many economic plants, such as yellowwood (Graney et al. 2016), hickory (Zhang et al. 2015) and larch (Rolim et al. 2020). To our knowledge, this is the first report of wilt on C. betulus caused by F. oxysporum in China.

Stem Canker on Cyclocarya paliurus Is Caused by Botryosphaeria dothidea.

Cyclocarya paliurus, an important endangered plant in China, has considerable medicinal, timber, and horticultural value. However, little is known about diseases that affect its health. In recent years, stem canker diseases on C. paliurus have been observed frequently in newly established nurseries in Jiangsu Province, China. Symptomatic trees showed elliptical, sunken lesions on the bark, with internal discoloration, leading to enlarging cankers with delineated margins. Pathogenicity tests with fungi isolated from symptomatic samples reproduced typical canker symptoms on both detached branches and potted plants of C. paliurus. Moreover, conidia from pycnidia of isolate ZB-23 could also cause stem canker on C. paliurus. Through combined morphological observation and DNA sequences of ITS region, ß-tubulin, and translation elongation factor 1-α genes, the pathogen was identified as Botryosphaeria dothidea. Multigene maximum likelihood and maximum parsimony phylogenetic analyses further supported the identification of the pathogen. To our knowledge, this is the first report of B. dothidea causing stem canker on C. paliurus in China.

[Hereditary hemorrhagic telangiectasia: a report of two cases].

This article reports two children with hereditary hemorrhagic telangiectasia (HHT). Patient 1 was a boy aged 12 years and was admitted due to intermittent cough and wheezing for more than 10 years. This boy and his mother and grandmother had a history of epistaxis. The boy had a history of the rupture of cerebral arteriovenous malformations. Gene detection showed a heterozygous mutation, c.277C>T(p.Arg93*), in the ENG gene. Patient 2 was a girl aged 13 years and was admitted due to cyanosis of lips for more than 1 year. The girl had a history of recurrent epistaxis and the manifestations of severe decline in pulmonary diffuse function, pulmonary hypertension, dilation of blood vessels at the distal end of lungs, and small arteriovenous communications in both lungs. Children with HHT often lack typical respiratory symptoms, which may lead to missed diagnosis and misdiagnosis in the early stage. Pulmonary computed tomography or right cardiac acoustic contrast can help with the diagnosis of HHT, and gene detection can improve the early diagnostic rate of this disease.

[Clinical features of neuroendocrine cell hyperplasia of infancy].

OBJECTIVE: To study the clinical features of neuroendocrine cell hyperplasia of infancy (NEHI) in order to provide a basis for the management of diagnosis, treatment and prognosis of children with NEHI. METHODS: A retrospective analysis was performed for the clinical data of seven children with NEHI who were diagnosed and treated from January 2014 to March 2016. RESULTS: Among the seven children with NEHI, there were five boys and two girls. Two children experienced tachypnea since the neonatal period, and five children developed respiratory tract symptoms within 1-6 months after birth. Of the 7 children, 6 had pulmonary crackles, 4 had hypoxemia, and 3 had gastroesophageal reflux. Lung high-resolution CT (HRCT) showed ground-glass opacities in the central region of the lungs in all children, which involved at least two lung lobes. Of the 7 children, 2 had the involvement of more than 4 lobes and 6 had air trapping. All 7 children had an improvement in clinical symptoms after two years of age. One child achieved clinical and CT remission. Four children achieved clinical remission, but still with CT changes. CONCLUSIONS: NEHI often occurs in infancy, with the major clinical manifestations of persistent tachypnea, pulmonary crackles, and hypoxemia. The children with NEHI often present ground-glass opacities in the central region of the lungs and air trapping on HRCT. There is no specific treatment for this disease and most cases have a good prognosis.

[Management plan for prevention and control of novel coronavirus pneumonia among children in Xiangya Hospital of Central South University].

Since December 2019, an epidemic of novel coronavirus pneumonia (NCP) has occurred in China. How to effectively prevent and control NCP among children with limited resources is an urgent issue to be explored. Under the unified arrangement of the Xiangya Hospital of Central South University, the Department of Pediatrics has formulated an action plan with Xiangya unique model to prevent and control NCP among children according to the current epidemic situation and diagnostic and therapeutic program in China.

[Cyanosis for more than 4 years in a girl aged 4 years and 3 months].

A girl, aged 4 years and 3 months, presented with cyanosis of the lips shortly after birth. She then experienced shortness of breath after activity 1 year ago and acrocyanosis 3 months ago, with obvious acropachy and toe deformity. Laboratory examinations revealed an increase in hemoglobin (178 g/L) and a reduction in arterial partial pressure of oxygen (37.7 mm Hg). Plain and contrast-enhanced CT scans of the lungs showed a large area of dense shadow and multiple nodules with clear boundaries in the right lower lung, as well as thickening of the arteries and dilatation of the veins in the right lower lung. Magnetic resonance angiography of the pulmonary artery showed large arteriovenous malformation in the lung. The child was diagnosed with congenital pulmonary arteriovenous fistula and was given interventional embolization of the pulmonary arterial fistula. The child was followed up at 3 months after surgery. The symptoms of shortness of breath and cyanosis disappeared, and activity tolerance, heart rate, hemoglobin, red blood cell count, and transcutaneous oxygen saturation all returned to normal.

[Acute fever with rash, necrosis, and bullae in both lower extremities in a 12-year-old girl].

A girl, aged 12 years, was admitted due to fever and rash for 3 days. The child developed recurrent high fever and rash on both lower extremities 3 days before, and the rash on left lower extremity quickly merged into a patch within 24 hours, with hemorrhage and necrosis in black and purple, large vesicles, and blisters in the center. Laboratory examination showed a reduction in platelet count and significant increases in fibrinogen and D-dimer during the course of the disease. The child was diagnosed with purpura flulminans. She was given meropenem combined with linezolid for anti-infection, injection of gamma globulin for immunoregulation, and low-molecular-weight heparin for anticoagulation. The fluid in the rash blisters was drawn and the wound was treated to prevent infection. The child's temperature returned to normal, with improvement in gangrene. She was discharged after platelet count, fibrinogen, and D-dimer had returned to normal. Purpura fulminans is a rare thrombotic hemorrhagic disease with rapid progression and is commonly seen in children. Without timely treatment, it may cause severe sequelae with high disability and mortality rates. Anti-infection, correction of coagulation function, and local management of gangrene skin are of great importance during treatment.

[Pyrexia and hemoptysis for eight days in a school-age child].

A girl was diagnosed with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) due to pyrexia and hemoptysis for eight days. The girl was a school-age child with major clinical manifestations of pyrexia, skin rash, enlargement of bilateral cervical lymph nodes, conjunctival hyperaemia, red and cracked lips and strawberry-like tongue, followed by swelling of both hands and feet. Laboratory examination showed significant increases in white blood cell count, platelet count, C-reactive protein, erythrocyte sedimentation rate and liver enzymes, a significant reduction in albumin, and the presence of aseptic pyuria. After the first course of IVIG treatment, the girl still had recurrent pyrexia, with hemoptysis on day 2 after admission, and lung CT showed uneven luminance and patchy shadow. The symptoms were quickly alleviated after the second course of IVIG treatment combined with methylprednisolone and aspirin treatment. KD is a febrile disease characterized by multiple systemic vasculitis in childhood and can involve various organ systems such as the heart, lungs, kidneys and the nervous system. Therefore, it is necessary to carefully monitor and recognize the rare symptoms of KD, and early recognition of pulmonary complications of KD can avoid delay in diagnosis, prevent the development of more serious complications, and help with early treatment and disease recovery.

[Levels of airway inflammatory mediators in peripheral blood in infants and young children with wheezing].

OBJECTIVE: To examine the levels of airway inflammatory mediators in peripheral blood in infants and young children with wheezing and to study the possible pathogenesis of wheezing from the aspects of T helper cell 1 (Th1)/T helper cell 2 (Th2) imbalance and airway inflammation. METHODS: A total of 50 children aged 1 month to 3 years with an acute wheezing episode were enrolled as the wheezing group, and 25 age-matched healthy infants were enrolled as the healthy control group. According to the number of wheezing episodes, the wheezing group was divided into a first-episode group (n=25) and a recurrent wheezing (number of episodes ≥2) group (n=25). According to the presence or absence of high-risk factors for asthma, the wheezing group was divided into a high-risk factor group (n=22) and a non-high-risk factor group (n=28). According to the results of pathogen detection, the wheezing group was divided into a positive pathogen group (n=23) and a negative pathogen group (n=27). Levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), transforming growth factor-ß1 (TGF-ß1), and total IgE (TIgE) in peripheral blood were measured for each group. For children with wheezing, eosinophil (EOS) count in peripheral blood was measured, and related samples were collected for respiratory pathogen detection. RESULTS: The wheezing group had significantly higher levels of IL-4, IL-5, IL-13, TGF-ß1, and TIgE in peripheral blood than the healthy control group (P<0.05). There were no significant differences in the levels of IL-2, IL-4, IL-5, IL-13, TGF-ß1, and TIgE in peripheral blood between the first-episode and recurrent wheezing groups, between the high-risk factor and non-high-risk factor groups, and between the positive pathogen and negative pathogen groups (P>0.05). The correlation analysis showed that in children with wheezing, EOS count was positively correlated with IL-4 level (P<0.01), IL-4 level was positively correlated with IL-5 and IL-13 levels (P<0.01), IL-5 level was positively correlated with IL-13 level (P<0.01), and IL-2 level was positively correlated with TGF-ß1 level (P<0.05). CONCLUSIONS: Th1/Th2 imbalance with a predominance of Th2 is observed in infants and young children with wheezing. IL-4, IL-5, IL-13, TGF-ß1, and IgE are involved in the pathogenesis of wheezing in these children. Airway inflammation is also observed in these children with wheezing, but it is not associated with the number of wheezing episodes, presence or absence of high-risk factors for asthma, or results of pathogen detection.

[Liver dysfunction for 8 years with hypertension for 1 week in an 8-year-old girl].

A girl, aged 8 years, developed jaundice and liver dysfunction in the neonatal period, with congenital glaucoma diagnosed on day 5 after birth, hypertension and unusual facies (broad forehead, hypertelorism and deep-set eyes). Cholestasis was the main type of liver dysfunction. Cardiac macrovascular CTA showed stenosis at the abdominal aorta and the beginning of the bilateral renal arteries. Whole exon sequencing revealed a heterozygous frameshift mutation, c.1485delC (absence of cytosine), in exon 12 of the JAG1gene. The girl was diagnosed with Alagille syndrome and was given transaminase-lowering, cholagogic and antihypertensive treatment with multiple drugs. There were significant reductions in serum levels of alanine aminotransferase, aspartate aminotransferase and total bile acid, but blood pressure fluctuated between 102-140 mm Hg/53-89 mm Hg. After renal artery angiography and balloon dilatation angioplasty, the girl was given oral administration of antihypertensive drugs, and blood pressure was controlled at a level of 110-120 mm Hg/60-80 mm Hg. The rare disease Alagille syndrome should be considered when a child has refractory hypertension with the involvement of multiple systems, especially liver dysfunction with cholestasis as the main manifestation. Genetic causes should be analyzed for a early diagnosis.

[Research advances in gene polymorphisms in biological pathways of drugs for asthma].

The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are ß2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

Alternaria alternata, the Causal Agent of a New Needle Blight Disease on Pinus bungeana.

Pinus bungeana, an endangered and native coniferous tree species in China, has considerable timber and horticulture value. However, little is known about needle diseases in P. bungeana. A needle blight of P. bungeana has been observed in Hebei Province, China. P. bungeana inoculated with mycelial plugs of fungal isolates presented symptoms similar to those observed under field conditions. Ten virulent fungal isolates were identified as a small-spored Alternaria species based on morphological observations. Maximum likelihood and Bayesian phylogenetic analyses carried out with multilocus sequence typing of eight regions (SSU, LSU, ITS, gapdh, tef1, Alt a 1, endoPG, OPA10-2) assigned the pathogen to Alternaria alternata. This is the first report of A. alternata causing needle blight on P. bungeana in China.

Cyclocarya paliurus Reprograms the Flavonoid Biosynthesis Pathway Against Colletotrichum fructicola.

Cyclocarya paliurus is an endemic Chinese tree species with considerable medicinal, timber, and horticultural value. The anthracnose disease of C. paliurus is caused by the fungal pathogen Colletotrichum fructicola, which results in great losses in yield and quality. Here, resistance evaluation of six cultivars of C. paliurus exhibited varying degrees of resistance to C. fructicola infection, where Wufeng was the most resistant and Jinggangshan was the most susceptive. Physiological measurements and histochemical staining assays showed that the Wufeng cultivar exhibits intense reactive oxygen species accumulation and defense capabilities. A multiomics approach using RNA sequencing and metabolome analyses showed that resistance in C. paliurus (Wufeng) is related to early induction of reprogramming of the flavonoid biosynthesis pathway. In vitro antifungal assays revealed that the flavonoid extracts from resistant cultivars strongly inhibited C. fructicola hyphal growth than susceptible cultivars. Relative gene expression analysis further demonstrated the pivotal antifungal role of C. paliurus flavonoids in targeting Colletotrichum appressorium formation. Together, these results represent a novel resistance mechanism of C. paliurus against anthracnose through the reprogramming of flavonoids, which will lay a foundation for breeding anthracnose-resistant varieties and the application of flavonoid extraction of C. paliurus as a natural antifungal treatment.

The role of ß-catenin signaling pathway on proliferation of rats neural stem cells after hyperbaric oxygen therapy in vitro.

ß-catenin, a protein that functions in both cell adhesion and Wnt signaling, plays a key role in mammalian neural development. To investigate the role of ß-catenin in hyperbaric oxygen therapy (HBO)-induced neurogenesis after hypoxic ischemic brain damage (HIBD), we transfected ß-catenin siRNA and negative control siRNA into neural stem cells (NSCs) after HIBD. We found that HBO promoted NSCs differentiate into neurons or oligodendrocytes, and inhibited NSCs differentiate into astrocytes; HIBD brain tissue extract conditioned cultures promoted NSCs differentiate into neurons; ß-Catenin siRNA decreased the NSE-positive neurons and increased GFAP-positive astrocytes in the NSCs in vitro. Furthermore, the expression of Ngn1 protein and mRNA in NSCs was increased when HBO promoted NSCs differentiate into neurons after HIBD, and the expression of BMP-4 protein and mRNA was decreased when HBO depressed NSCs differentiate into astrocytes after HIBD. These results showed that ß-catenin-mediated transcriptional activation functions in the decision of NSCs to proliferate neurogenesis during HBO-induced after HIBD, and suggested that HBO therapy promotes the proliferation of neural stem cells in vitro, an effect that may be correlated with ß-catenin protein and HBO therapy could promote neurogenesis by ß-catenin-induced activated Ngn1 gene and repress astrocytogenesis by ß-catenin-induced down-regulated BMP-4 gene.