A novel kinase subverts aluminium resistance by boosting ornithine decarboxylase-dependent putrescine biosynthesis.

Rice, as one of the most aluminium (Al)-resistant cereal crops, has developed more complicated Al resistance mechanisms than others. By using forward genetic screening from a rice ethyl methanesulfonate mutant library, we obtained a mutant showing specifically high sensitivity to Al. Through MutMap analysis followed by a complementation test, we identified the causal gene, Al-related Protein Kinase (ArPK) for Al-sensitivity. ArPK expression was induced by a relatively longer exposure to high Al concentration in the roots. The result of RNA-sequencing indicated the functional disorder in arginine metabolism pathway with downregulation of N-acetylornithine deacetylase (NAOD) expression and upregulation of Ornithine decarboxylase1 (ODC1) expression in arpk mutant. Al specifically and rapidly upregulated ODC1 expression and causes overaccumulation of putrescine (Put), whereas the ODC inhibitor difluoromethylornithine reverted Al-sensitive phenotype of arpk, suggesting that overaccumulation of endogenous Put might be harmful for root growth, and that ArPK seems to act as an endogenous inhibitor of ODC1 action to maintain suitable endogenous Put level under Al treatment. Overall, we identified ArPK and its putative repressive role in controlling a novel ODC-dependent Put biosynthesis pathway specifically affecting rice Al resistance, thus enriching the fundamental understanding of plant Al resistance.

[Analysis the influence factors of treatment free remission outcome with chronic myeloid leukemia patients who discontinued tyrosine kinase inhibitors].

Objective: To explore the related factors affecting the outcome of treatment free remission (TFR) in patients with chronic myeloid leukemia (CML). Methods: Clinical data of CML patients with automatic discontinuation of tyrosine kinase inhibitor (TKI) from the CML cooperative organization of Henan province between June 2, 2013 to March 27, 2021 and the follow-up time was ≥ 6 months were retrospectively analyzed. Log-rank test was used for univariate analysis and Cox proportional risk regression model was used for multivariate analysis. Results: A total of 135 patients were enrolled, and 69 patients (51.1%) were femal and 66 patients (48.9%)were male. Median age was[M(Q1,Q3)] 49 years (38, 58)at discontinuation.Before discontinuation, 72 patients (53.3%) were on treatment with second-generation TKI, 63 patients (46.7%) were on treatment with IM, 17patients (12.6%) had a history of TKI reduction/withdrawal;median duration of treatment was months 84 (68, 108) for all patients;median time of TKI treatment to DMR was months 12(8, 26);median duration of DMR was months 65 (54, 84), and 9 patients (6.7%) had unsustained DMR.The median follow-up time was months 16(6-96), 35 patients (25.9%) lost MMR at a median months 3(1-22), overall estimated TFR was 74.1%.The univariate analysis results showed that:second-generation TKI was used, the time of TKI treatment to DMR was ≤12 months, DMR duration time ≥48 months, had sustained DMR, without TKI reduction/withdrawal history were favorable factors affecting of TFR in patients with TKI discontinuation (all P<0.05).The TFR rate of the second-generation TKI therapy group was significantly higher than the IM therapy group (81.9% vs 65.1%, P=0.019).The multivariate analysis results showed that second-generation TKI treatment[RR=0.451, 95%CI (0.227-0.896), P=0.023] and had sustained DMR [RR=0.120, 95%CI (0.053-0.271), P<0.001] were the protective factors of TFR in patients with TKI discontinuation. Conclusions: Treated with second-generation TKI and had sustained DMR are the protective factors of TFR in patients with TKI discontinuation.The CML patients who had sustained DMR more≥48 months before TKI discontinuation showed a better TFR.

[Idiopathic pleuroparenehymal fibroelastosis: five case reports and review of literature].

Objective: To raise the awareness of idiopathic pleuroparenehymal fibroelastosis (iPPFE) through investigating the clinical, radiographic and pathological features. Methods: Five cases of iPPFE proved by pathology. The clinical data were studied respectively, and the relevant literature was reviewed. Results: All the cases of iPPFE were manifested by cough and dyspnea. The patients including 3 males and 2 females, aged from 30 to 70 years Chest CT scan showed pleural thickening, subpleural consolidation in both upper lungs complicated with tractive bronchiectasis.Computed tomography-guided percutaneous lung biopsy or surgical lung were performed and the same pathological showed pleura and subpleural dense elastic and collagen fibers. The elastic fibers stain was also positive,which was consistent with PPFE. One patient received low-dose corticosteroid, two received pirfenidone therapy, the others received no treatment. Three patients were stable during the follow-up. Conclusions: iPPFE has characteristic pathological features. However, the number of clinically reported cases is low due to missed diagnosis or misdiagnosed. Improving the understanding of features of iPPFE is helpful for the dianosis, therapy, and prognosis of this disease.

[Short-term outcomes of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with spondyloepiphyseal dysplasia].

OBJECTIVE: Severe hip osteoarthritis, caused by bone or joint maldevelopment, biomechanical transformation and previous surgical intervention, is inclusively existed in spondyloepiphyseal dysplasia (SED). To investigate and discuss the short-term efficacy and possible effects of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with SED. METHODS: From January 2017 to June 2019, 374 patients with hip osteoarthritis were involved for total hip arthroplasty conducted by senior professional surgeons, of whom 9 patients (6 males and 3 females) with 12 hip osteoarthritis secondary to the SED met the inclusive and exclusive criteria and received the above-mentioned hip operation. The short-term outcomes were observed. RESULTS: All the patients were implanted with Johnson & Johnson ceramic on ceramic cementless hip prostheses within the arthroplasty. They were followed up for an average period of 20 months. Except for one muscular calf vein thrombosis case, no complications, such as aseptic loosening, joint dislocation, fracture, neurovascular injury, deep vein thrombosis and infection were observed in all the 9 patients. Before the surgery, the average Harris hip score was 35.55, while the average of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was 56.56. The level of quality of life indicated by SF-12 score was 41.56 on average. The mean pre-operation visual analogue scale (VAS) was 7.44. At the last follow-up, the average Harris hip score increased to 89.56, whereas the average WOMAC declined to 41.11. Compared with the baseline point, the average SF-12 score went up to 56.33. Dramatic drop of the mean VAS value to 2.67 was also observed at the last follow-up. In addition, post-operative increase of several pelvic-related parameters including pelvic incidence, pelvic tilt and sacral slope could be observed in the SED patients. The average measured pelvic incidence, pelvic tilt and sacral slope were 68.95°±4.60°, 52.75°±1.06° and 17.45°±1.77° before operation, respectively; whilst the mean value of these specific parameters increased to 76.98°±5.12°, 60.51°±4.35° and 18.10°±2.02°, respectively. The even leg lengths of the lower extremities were obtained after total hip arthroplasty. CONCLUSION: Total hip arthroplasty is satisfactory in the short-term pain relieve and function recovery for the management of Tönnis grade 3 hip osteoarthritis secondary to the SED.

Renpenning syndrome in a female.

Renpenning syndrome (OMIM: 309500) is a rare X-linked disorder that causes intellectual disability, microcephaly, short stature, a variety of eye anomalies, and characteristic craniofacial features. This condition results from pathogenic variation of PQBP1, a polyglutamine-binding protein involved in transcription and pre-mRNA splicing. Renpenning syndrome has only been reported in affected males. Carrier females do not usually have clinical features, and in reported families with Renpenning syndrome, most female carriers exhibit favorable skewing of X-chromosome inactivation. We describe a female with syndromic features typical of Renpenning syndrome. She was identified by exome sequencing to have a de novo heterozygous c.459_462delAGAG mutation in PQBP1 (Xp11.23), affecting the AG hexamer in exon 4, which is the most common causative mutation in this syndrome. Streaky hypopigmentation of the skin was observed, supporting a hypothesized presence of an actively expressed, PQBP1 mutation-bearing X-chromosome in some cells. X-inactivation studies on peripheral blood cells demonstrated complete skewing in both the proband and her mother with preferential inactivation of the maternal X chromosome in the child. We demonstrated expression of the PQBP1 mutant transcript in leukocytes of the affected girl. Therefore, it is highly likely that the PQBP1 mutation arose from the paternal X chromosome.

A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.

BACKGROUND: Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification). METHODS: The study was conducted in three phases: 1) development - an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification; 2) validation - using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined; 3) reproducibility - the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module. RESULTS: The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73 - 0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively. CONCLUSION: We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module.

[The clinical significance of myositis-specific antibodies in polymyositis/dermatomyositis associated interstitial lung diseases].

Objective: To investigate the profile and clinical significance of myositis-specific antibody spectrum (MSAs) in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). Methods: Sera from 74 patients with PM/DM-ILD, 29 patients with SLE and 32 healthy controls were collected and Euroline Autoimmune Inflammatory Myopathies 16 Ag kit was used for detecting MSAs . The clinical data of all patients were collected from medical records. Statistical analysis was performed using One-way ANOVA, t-test, rank sum test, χ(2) test or Fisher's exact test. Results: The overall detection rate of MSAs in 74 patients with PM/DM-ILD was 86.5%, significantly higher than that in patients with SLE and healthy controls (χ(2)=66.24, 69.85, P<0.01). According to the diagnostic criteria of PM/DM, 18 of 74 patients were definitely diagnosed, 11 were preliminarily diagnosed and 45 were suspected, in which the detection rate of MSA was 83.3%, 90.9% and 86.7%, respectively .The detection rates of MSAs in 17 PM-ILD and 57 DM-ILD were 82.4% and 87.7% respectively. The anti-ARS and anti-MDA5 were the two most common subtypes of MSAs in patients with PM/DM-ILD, the positive rates being 59.5% and 25.7%, respectively . The incidence of CADM, acute/subacute ILD and 90-day mortality in the anti-MDA5 positive group (χ(2)=12.945, 23.203, 26.434, P<0.05) was significantly higher than those of the anti-ARS group and the MSA-negative group, while the incidence of helitrope rash, V-rash, fever was significantly higher than the anti-ARS positive group (χ(2)=11.462, 5.895, 10.609, P<0.05). The incidence of muscle weakness in anti-Jo-1 group was significantly higher than that in the non-Jo-1 antibody group (χ(2)=3.991, P<0.05), while other clinical features were not statistically significant between the anti-Jo-1 and the non-Jo-1 anti-ARS positive groups (P>0.05). Conclusion: The detection rate and accuracy of MSAs in polymyositis/dermatomyositis with ILD was very high, which was useful for early diagnosis of the disease, and severity and prognosis assessment. It is strongly recommended that MSAs should be detected in patients with clinical suspicion of PM/DM-associated interstitial lung diseases.

[Clinicpathological features and survival of patients with AIDS related non-Hodgkin's lymphoma].

Objective: To analyze the clinical characteristics, pathological features and survival of patients with AIDS related non-Hodgkin's lymphoma (ARL) . Methods: The clinical data of 53 ARL cases diagnosed and received care at Zhongnan hospital of Wuhan University were retrospectively studied, and 106 controls were enrolled as control group according to 1∶2 for paired cases and control. SPSS 13.0 package was used for statistical analysis. Kaplan-Meier was applied to assess the survival probability. Results: The mean age of patients with ARL was 43 (11-67) years. Male versus female was approximately 4∶1. The median CD4(+) T cell count was (146±20) /ml. The Ann Arbor clinical classification showed that 52.8% of the cases were of stage Ⅲ and Ⅳ. Approximately 54.7% of the patients had elevated serum lactate dehydrogenase (LDH) . According to international prognosis index score, 64.2% of the patients were in high risk group. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype. Among 53 cases, 33 cases (62.3%) received combination of anti-HIV therapy and anti-NHL (CHOP) chemotherapy regimen, 8 cases (15.1%) only received anti-HIV therapy, and 12 cases (22.6%) asked for alleviative treatment. Median survival time was (6.0±1.3) months for ARL cases versus (48.0±10.0) months for controls (P<0.05) . After eliminating cases who did not receive anti-lymphoma treatment, ARL cases showed a lower 1-year OS rates than control group (60.6% versus 83.0%) , but no difference about 2-, 3- and 5-year OS rates (53.5% versus 60.5%, 48.1% versus 45.9%, and 39.1% versus 27.5%, respectively) . Conclusions: ARL is more common in young adults; one-year mortality rate is high. Anti-HIV therapy combined with anti-NHL therapy could significantly improve the prognosis of ARL patients. CHOP regimen may be more suitable for ARL patients.

[Unilateral pleural effusion as first manifestation in Takayasu arteritis: a case report and review of literature].

Objective: To highlight the characteristics of pulmonary arterial involvement in Takayasu arteritis. Methods: The clinical and radiological data of a patient with Takayasu arteritis presenting with unilateral pleural effusion were studied and relevant literature was reviewed. The key words, "Takayasu arteritis" and "pleural effusion" were analyzed through literature retrieval in databases. Results: This 58 year-old female patient presented with shortness of breath. The chest CT scan showed bilateral hilar enlargement and pleural effusion on the left side. The blood pressure was not measurable in the course of the disease. After the aorticopulmonary-arteriography, we found that the pulmonary artery and the subclavian artery were involved. The diagnosis of Takayasu arteritis was made, and glucocorticoid therapy was initiated, with significant clinical and radiological improvement after therapy. Literature review found 4 cases of Takayasu arteritis with unilateral pleura effusion, ranging from 32 to 35 years of age, with a female predominance(Female∶Male=3∶1). The chief complaints were fever, chest pain and hemoptysis. All the patients recovered after the treatment of glucocorticoids. Conclusions: Takayasu arteritis presenting with unilateral pleural effusion was easily misdiagnosed as primary pulmonary diseases. Careful physical examination and timely angiography can be used to make the diagnosis.

Maternal anti-HBVs suppress the immune response of infants to hepatitis B vaccine.

It is still controversial whether maternal anti-HBV antibodies (anti-HBVs) affect the infants' immune response to hepatitis B virus (HBV) vaccination. This multicentre study aims to address this question. First, we determined whether the transplacental transfer of maternal anti-HBVs occurs by measuring the titres of 90 anti-HBVs-positive pregnant women and their newborns. The anti-HBVs-positive rates of newborns ranged from 89.7% to 100.0%, depending on the maternal anti-HBVs titres. Secondly, we investigated the effects of maternal anti-HBVs on the immune response of infants to HBV vaccination. A total of 1063 mother-and-infant pairs were enrolled and divided into three groups with maternal anti-HBVs titres of <10 IU/L (negative - 37.9%), 10-499 and ≥500 IU/L. The infants' anti-HBVs-positive rate and titres were negatively correlated with maternal anti-HBVs titres: the anti-HBVs-positive rate of infants were 88.9% (360/405), 84.5% (381/451) and 77.3% (160/207) in mothers with low, intermediate and high antibody titres, respectively, P<.0001. Median titres of anti-HBVs (IU/L) among infants were 169.1, 141.0 and 79.4, respectively, P=.020. One hundred and sixty-two infants were negative for anti-HBVs after the standard vaccination, and 120 of 131 of these infants (91.6%) reached anti-HBVs positivity after the first "booster" dose. The maternal anti-HBVs titres did not significantly affect infant response to this booster. In summary, transplacental transfer of anti-HBVs occurs and high titres of maternal anti-HBVs may suppress the immune response of infants to the standard HBV vaccination. The current schedule of the 0, 1 and 6 month may not be the optimal choice of infants with anti-HBVs-positive mothers.

[Comparison of naming impairment among patients with Parkinson's disease without dementia, Parkinson's disease dementia and Alzheimer's disease].

OBJECTIVE: To compare the characteristics of naming impairment in Parkinson's disease (PD) without dementia, Parkinson's disease dementia (PDD) and Alzheimer's disease (AD). METHODS: All participants came from outpatient clinic or inpatients of our hospital during 2011-2013. Object and action naming tests were evaluated among patients with PD without dementia (n=60), PDD (n=60), AD (n=60) and healthy control group (n=60). RESULTS: The object naming score of PD without dementia group was 40.2±2.8, PDD group was 36.0±3.1, AD group was 31.6±4.0 and healthy control group was 44.1±2.2, while the action naming score of PD without dementia group was 27.3±2.6, PDD group was 20.5±4.0, AD group was 22.5±2.7 and healthy control group was 31.6±1.4. The object and action naming were both impaired in PD without dementia, PDD and AD patients compared with healthy control group (P<0.01). CONCLUSIONS: PD patients without dementia have slight object and action naming impairments with more impairments in action naming. Action naming is more impaired in PDD patients, while object naming is more impaired in AD patients.

High definition i-SCAN endoscopy with water immersion technique accurately reflects histological severity of celiac disease.

BACKGROUND AND AIMS: Severe villous atrophy can be revealed with conventional white light endoscopy (WLE), however, milder grades or patchy villous atrophy are more difficult to detect. Novel endoscopic techniques such as high definition i-SCAN endoscopy with the water immersion technique (i-SCAN-HDWI) may provide the ability to visualize duodenal villi more accurately. We aimed to determine the performance of i-SCAN-HDWI in evaluating the severity of histological damage in the duodenum of patients with celiac disease. PATIENTS AND METHODS: A retrospective cohort study was performed in a single tertiary academic endoscopic center. We studied 58 patients (46 women; median age 36.5 years, range 18 - 72 years) with positive anti-TTG IgA antibody. The villous pattern of the second part of the duodenum was assessed by WLE and i-SCAN-HDWI. The endoscopic grades in both techniques were correlated using Marsh histologic grades by Spearman correlation coefficient. The diagnostic accuracy of i-SCAN-HDWI for detection of patchy or complete atrophy of the villi was evaluated. RESULTS: A significant correlation was demonstrated between endoscopic grade using i-SCAN-HDWI and Marsh histologic grade (r = 0.732; P < 0.00001). The correlation between WLE grade and Marsh histologic grade was inferior to i-SCAN-HDWI (r = 0.31; P = 0.01). The sensitivity of i-SCAN-HDWI was 96 % (95 %CI: 85 - 99 %) and the specificity was 63 % (95 %CI: 26 - 90 %) in diagnosing abnormal biopsy consistent with celiac disease. CONCLUSION: i-SCAN-HDWI endoscopy can reflect the histological severity of celiac disease more accurately than conventional WLE alone. This novel endoscopic imaging can improve the diagnostic yield of duodenal biopsies in celiac patients, especially for those with a patchy distribution of villous damage.

[The prevalence of allergy-related symptoms and their risk factorinvestigation in early life].

Objective:The aim of this study is to investigate the incidence of allergy-related symptoms and the associated risk factors.Method:There were 205 children aged 3 to 4 years old recruited for this study.Questionnaires on skin,wheezing and rhinitis symptoms were answered,and total IgE and specific IgE in serum against house dust mite extracts were tested.Logistic regression analysis with which we calculated odds ratio(OR) and 95% confidence interval(95%CI) were used for risk factor analysis.Result:Questionnaire results show that the reported history of symptoms was 43%(88 cases) for lactation eczema and 25%(51 cases) for wheezing.The currently reported symptoms was 19%(38 cases) for frequent skin rashes,16% (33 cases) for frequent wheezing and 46%(95 cases) for rhinitis symptoms.There are 33% (68 cases) of the children reported with no symptoms currently.The lactation eczema history(ORï¼»95%CIï¼½:2.76ï¼»1.10-3.40ï¼½,P<0.05)and wheezing history(ORï¼»95%CIï¼½:2.40ï¼»1.22-4.73ï¼½,P<0.01)are both the risk factors for developing rhinitis symptoms.Serology test shows that house dust mite IgE prevalence is 24%,which is the risk factor developing rhinitis symptom(ORï¼»95%CIï¼½:2.10ï¼»1.09-4.07ï¼½,P<0.05).But it has nothing to do with wheezing symptom.Conclusion:Lactation eczema and house dust mite sensitization are the risk factors for developing respiratory diseases in early childhood.The house dust mite allergic respiratory symptom starts with rhinitis symptom.

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study.

BACKGROUND AND PURPOSE: Convergent evidence indicates that HIV is associated with abnormal WM microstructure in adults. However, little is known about whether HIV affects WM development in adolescents. In this study, we used DTI to investigate the integrity of WM microstructure in adolescents with vertically transmitted HIV infections. MATERIALS AND METHODS: Fifteen HIV-positive adolescents with vertically transmitted infections and 26 HIV-negative controls participated in this study. Whole-brain analysis of fractional anisotropy was performed by Tract-Based Spatial Statistics to localize abnormal WM regions between groups. VOI analysis was further performed to explore the changes in diffusivity indices in the regions with fractional anisotropy alterations. Correlation analyses were used to assess the relationship between fractional anisotropy alterations and clinical measures within the HIV-positive group. RESULTS: Relative to HIV-negative controls, HIV-positive adolescents demonstrated significantly reduced fractional anisotropy in the corpus callosum, superior and posterior corona radiata, frontal and parietal WM, pre-/postcentral gyrus, and superior longitudinal fasciculus. In the affected regions, fractional anisotropy reductions were caused by an increase in radial diffusivity, and no changes were observed in axial diffusivity. Moreover, fractional anisotropy values in the bilateral frontal WM were negatively correlated with the duration of highly active antiretroviral therapy and were positively associated with the age at onset of highly active antiretroviral therapy. CONCLUSIONS: These findings suggest that early HIV infections may affect WM development, especially in the frontal WM, corpus callosum, and corona radiata in adolescents, which may be associated with hypomyelination and demyelination. Moreover, WM integrity may serve as a potential new treatment target.

Species-specific differences in the expression and regulation of α4ß7 integrin in various nonhuman primates.

Among nonhuman primates, SIV-infected Asian pigtailed macaques (PM) are relatively more susceptible to infection and disease progression than SIV-infected rhesus macaques (RM). In addition, SIV-infected African natural hosts such as the sooty mangabeys (SM) are resistant to disease. The mechanisms associated with such species-related variable clinical outcomes remain ill-defined but hold the potential to provide insights into the underlying mechanisms surrounding HIV pathogenesis. Recent findings indicate that the expression of the heterodimeric gut homing integrin α4ß7 can influence both susceptibility and disease progression in RM. It was reasoned that differences in the frequencies/surface densities of α4ß7-expressing lymphocytes might contribute to the differences in the clinical outcome of SIV infection among NHPs. In this article, we report that CD4(+) T cells from PM constitutively express significantly higher levels of α4ß7 than RM or SM. Retinoic acid, a key regulator of α4ß7 expression, was paradoxically found at higher levels in the plasma of SM versus RM or PM. We also observed pairing of ß7 with αE (αEß7) on CD4(+) T cells in the peripheral blood of SM, but not PM or RM. Finally, the differential mean density of expression of α4ß7 in RM versus SM versus PM was predominantly dictated by species-specific sequence differences at the level of the ß7 promoters, as determined by in vitro reporter/promoter construct transfection studies. We propose that differences in the regulation and expression of α4ß7 may explain, in part, the differences in susceptibility and SIV disease progression in these NHP models.