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Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disease characterized by progressive lower limb spasticity. Recent studies revealed that biallelic variants in RNF170 gene cause autosomal recessive complicated HSP with infancy onset. Here, we report an adolescent-onset HSP patient from a consanguineous Chinese family, with lower extremity stiffness, spastic gait, and unstable straight-line walking as the main manifestations. Whole-exome sequencing identifies a novel RNF170 mutation c.190CT (p.R64*), which co-segregates with the disease in this pedigree. Functional analysis, including quantitative real-time PCR (RT-qPCR) and Western blot, indicates that both the mRNA and protein levels of mutant RNF170 are significantly reduced, which confirms the loss-of-function mechanism. Our study expands the spectrum of RNF170-associated HSP, while the RNF170 protein-involved degradation of the inositol 1,4,5-trisphosphate receptor in neurodegenerative motor neuron disorders deserves further investigation.

Mutations in proline-rich transmembrane protein 2 (PRRT2) are the major cause of paroxysmal kinesigenic dyskinesia (PKD). We recently reported transmembrane protein 151A (TMEM151A) mutations caused PKD. Herein, we aimed to conduct phenotypic comparisons of patients with PKD carrying PRRT2 variants, carrying TMEM151A variants, and carrying neither the PRRT2 nor TMEM151A variant.Sanger sequencing of PRRT2 and TMEM151A was performed, and phenotypic characteristics were analyzed.In a cohort of 131 PKD probands (108 without PRRT2 variants and 23 newly recruited), five novel TMEM151A variants were identified and one (c.647C A) occurred de novo. Together with our previous studies, PRRT2 and TMEM151A variants accounted for 34.7% (85/245) and 6.9% (17/245) of PKD probands, respectively. Compared with patients carrying PRRT2 variants, those with TMEM151A variants tended to exbibit dystonia with shorter durations, have no history of benign infantile epilepsy, and have residual attacks/aura when treated with carbamazepine/oxcarbazepine.Patients with TMEM151A variants have different features from patients with PRRT2 variants. © 2022 International Parkinson and Movement Disorder Society.

An unprecedented four-component defluorinative reaction of allylic fluorides, amidines, and Cs2CO3 for the convenient synthesis of valuable pyrimidine-containing amidino carbamates under transition-metal-free conditions was developed.

An efficient transition-metal-free hydrodefluorination reaction of trifluoromethyl alkenes for accessing gem-difluoroalkenes is developed. It was surprising to find that the phosphoryl anion is able to mediate the defluorination.

Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (K(D)) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-φ1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the α2-, α3-, and α4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. IMPORTANCE The matrix protein of SVCV (SVCV-M) is an indispensable structural element for nucleocapsid condensation and virion formation during viral morphogenesis, and it connects the core nucleocapsid particle to the outer membrane within the mature virus. Previous studies have emphasized the architectural role of SVCV-M in viral construction; however, the potential nonstructural functions of SVCV-M in viral replication and virus-host interactions remain poorly understood. In this study, we identified the inhibitory role of the SVCV-M protein in host IFN production by competitively recruiting TRAF3 from the MAVS signaling complex and impairing TRAF3 activation via inhibition of K63-linked polyubiquitination. This finding provided new insights into the regulatory role of SVCV-M in host innate immunity, which highlighted the broader functionality of rhabdovirus matrix protein apart from being a structural protein. This study also revealed a previously unrecognized mechanism underlying SVCV immune evasion by inhibiting the IFN response by targeting the MAVS/TRAF3 signaling axis.

BACKGROUND Since December 2019, there have been many new cases of coronavirus pneumonia in Wuhan, Hubei Province, which has gradually spread throughout the country. AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic, since controlling the spread of disease is an important way to prevent and control the epidemic. METHODS In total, 200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups. RESULTS The fever clinic in our hospital operated smoothly, and infection with the novel coronavirus disease (COVID-19) has not been reported in our hospital. Additionally, we did not have any cases of missed diagnosis. The awareness regarding COVID-19 infection sources, transmission routes, early symptoms, and preventive measures was significantly higher in our fever clinic than in those of the pre-management group. CONCLUSION "An integrated system, three separate responsibilities" ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases, which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital, ultimately achieving the maximum effect of epidemic prevention and control.

The proteins with DNA-binding preference to the consensus DNA sequence (A/T) GATA (A/G) belong to a GATA transcription factor family, with a wide array of biological processes in plants. Cassava (Manihot esculenta) is an important food crop with high production of starch in storage roots. Little was however known about cassava GATA domain-containing genes (MeGATAs). Thirty-six MeGATAs, MeGATA1 to MeGATA36, were found in this study. Some MeGATAs showed a collinear relationship with orthologous genes of Arabidopsis, poplar and potato, rice, maize and sorghum. Eight MeGATA-encoded proteins (MeGATAs) analysed were all localized in the nucleus. Some MeGATAs had potentials of binding ligands and/or enzyme activity. One pair of tandem-duplicated MeGATA17–MeGATA18 and 30 pairs of whole genome-duplicated MeGATAs were found. Fourteen MeGATAs showed low or no expression in the tissues. Nine analysed MeGATAs showed expression responses to abiotic stresses and exogenous phytohormones. Three groups of MeGATA protein interactions were found. Fifty-three miRNAs which can target 18 MeGATAs were identified. Eight MeGATAs were found to target other 292 cassava genes, which were directed to radial pattern formation and phyllome development by gene ontology enrichment, and autophagy by Kyoto Encyclopaedia of Genes and Genomes enrichment. These data suggest that MeGATAs are functional generalists in interactions between cassava growth and development, abiotic stresses and starch metabolism.

Soil conservation practices can greatly affect the soil erosion process, but limited information is available about its influence on the particle size distribution (PSD) of eroded sediment, especially under natural rainfall. In this study, the runoff, sediment yields, and effective/ultimate PSD were measured under two conventional tillage practices, downhill ridge tillage (DT) and plat tillage (PT) and three soil conservation practices, contour ridge tillage (CT), mulching with downhill ridge tillage (MDT), and mulching with contour ridge tillage (MCT) during 21 natural rainfall events in the lower Jinsha River. The results showed that (1) soil conservation practices had a significant effect on soil erosion. The conventional tillage of DT caused highest runoff depth (0.58 to 29.13 mm) and sediment yield (0.01 to 3.19 t hm−2). Compared with DT, the annual runoff depths and sediment yields of CT, MDT and MCT decreased by 12.24%–49.75% and 40.79%–88.30%, respectively. (2) Soil conservation practices can reduce the decomposition of aggregates in sediments. The ratios of effective and ultimate particle size (E/U) of silt-and sand-sized particles of DT and PT plots were close to 1, indicating that they were transported as primary particles, however, values lower/greater than 1 subject to CT, MDT and MCT plots indicated they were transported as aggregates. The ratios of E/U of clay-sized particles were all less than 1 independently of tillage practices. (3) The sediments of soil conservation practices were more selective than those of conventional tillage practices. For CT, MDT and MCT plots, the average enrichment ratios (ERs) of clay, silt and sand were 1.99, 1.93 and 0.42, respectively, with enrichment of clay and silt and depletion of sand in sediments. However, the compositions of the eroded sediments of DT and PT plots were similar to that of the original soil. These findings support the use of both effective and ultimate particle size distributions for studying the size selectivity of eroded sediment, and provide a scientific basis for revealing the erosion mechanism in the purple soil area of China.

The objective of this study was to determine the distribution of cadmium (Cd) accumulation in tobacco and identify the relationship between soil properties and plant Cd concentration. Forty soil and tobacco samples were collected from the Sichuan Basin, China (Panzhihua, Luzhou, Guangyuan and Yibin). The results showed the highest Cd in soil (2.94 mg kg−1) was in Yibin. Correspondingly, Cd concentrations in tobacco from Yibin were significantly higher than those from the other regions. The Cd concentrations in tobacco from Yibin, Luzhou, Guangyuan and Panzhihua were from 2.22 to 13.14, 0.59 to 2.12, 0.26 to 0.61, 0.10 to 0.37 mg kg−1, respectively. The Cd concentrations in leaves were higher than those in stems and roots. The highest Cd concentrations were in lower leaves, between 0.36 and 13.14 mg kg−1. In Yibin, the Cd in lower leaves nearly exceeded 10 mg kg−1 and the ratio of the Cd tobacco and soil concentrations (the bioconcentration factor, BCF) was 9.41. Path analysis showed soil pH and cation exchange capacity (CEC) were the most significant properties exhibiting direct effects on Cd accumulation. Stepwise multiple linear regression showed that soil Cd, pH, CEC and organic carbon (OC) were the major factors controlling Cd bioavailability to tobacco leaves, explaining more than 94.0% of the variance. The results are useful in predicting the transfer of Cd from soil to tobacco.

Importance: The Mini-Clinical Evaluation Exercise (Mini-CEX) is highly recommended for assessing interns’ performance. Objective: To develop a pediatric occupational therapy–specific Mini-CEX and examine its psychometrics. Design: Stage 1 had a retrospective design; Stage 2 had a prospective design. Setting: Pediatric occupational therapy unit in a hospital in Taiwan. Participants: Thirty-four occupational therapy interns were evaluated with the Mini-CEX (physician version), and 57 were evaluated with the occupational therapy–specific Mini-CEX. Outcomes and Measures: The occupational therapy–specific Mini-CEX was developed with seven items on a 9-point scale categorized into three levels (unsatisfactory, satisfactory, highly satisfactory). Results: In Stage 1, the frequency of Mini-CEX (physician version) items receiving a rating of not applicable ranged from 1.9% to 88.1%. In Stage 2, the frequency of occupational therapy–specific Mini-CEX items receiving a rating of not applicable ranged from 3.5% to 31.6%. With the theme of evaluation taken into consideration, the frequency of not-applicable ratings was 0% to 8.8%. For the occupational therapy–specific Mini-CEX, content validity (item-level content validity index = 1, scale-level content validity index = 1) and internal consistency (Cronbach’s α = .93) were excellent. The interns’ scores on the second evaluation were significantly higher than those on their first evaluation, indicating good discriminant validity. Conclusions and Relevance: The occupational therapy–specific Mini-CEX appears to be reliable and valid, and it is appropriate for evaluating interns’ skills and attitudes in pediatric occupational therapy practice. What This Article Adds: The results support the development of the occupational therapy–specific Mini-CEX and its application in pediatric internship training.

Importance: Early identification of young children at risk of developmental coordination disorder (DCD) can support early intervention and prevent secondary sequelae. Objective: To examine the psychometric properties of a translated and cross-culturally adapted version of the Little Developmental Coordination Disorder Questionnaire–Taiwan (LDCDQ–TW). Design: Prospective study. Setting: Kindergartens and preschools in north, central, and south Taiwan. Participants: In Phase 1 the participants were 1,124 parents of typically developing children ages 36–71 mo. Children with confirmed developmental diagnoses were excluded. Participants in Phase 3 were 162 children who had been recruited in Phase 2. Outcomes and Measures: The LDCDQ–TW, a 15-item parent questionnaire for identifying children at risk for DCD, and the Movement Assessment Battery for Children (2nd ed.; MABC–2), were administered. Results: The findings revealed excellent test–retest reliability (intraclass correlation coefficient [ICC] = .97) and poor interrater reliability (ICC = .47). On the basis of MABC–2 scores, the non-DCD group (≥15th percentile) scored significantly higher than the DCD and suspect-DCD groups on the LDCDQ–TW, but the latter two groups did not differ from one another. Using the 15th percentile as a cutoff for both the MABC–2 and the LDCDQ–TW, sensitivity was .96 and specificity was .68. Conclusions and Relevance: Although standardized performance-based assessments are required to confirm a diagnosis of DCD (typically after age 5 yr), the LDCDQ–TW demonstrated sound reliability and validity and can support the early identification of young children at risk of DCD in Taiwan. What This Article Adds: The LDCDQ–TW can facilitate early intervention for DCD and prevent secondary sequelae, improving outcomes for children with DCD.

Background Previous studies have demonstrated that Ro60 and Ro52 have different clinical implications, and anti‐Ro52 antibodies are an independent serum marker of systemic autoimmune diseases, including Sjögren's syndrome. Many different assays have been adopted to detect anti‐Sjögren's syndrome antigen A (SSA)/Ro antibodies, while to date no specific approach has been recommended as optimal for anti‐SSA/Ro antibody testing. Herein, we performed a multi‐center study to explore the current clinical utility of different strategies for anti‐SSA/Ro antibody testing in China. Methods Twenty‐one tertiary care centers were included in this questionnaire‐based study. The self‐administered questionnaire mainly includes testing methods for anti‐SSA/Ro antibodies, reporting system of results, and interpretation of results by clinicians. Results Six different methods were applied to detect anti‐SSA/Ro antibodies in the 21 centers. Line immunoassay (eight different commercial kits) was the most frequently adopted method (21/21, 100%), with different cutoff values and strategies for intensity stratification. There were two reporting systems: One was reported as “anti‐SSA antibodies” and “anti‐Ro52 antibodies” (12/21, 57%), while the other was “anti‐SSA/Ro60 antibodies” and “anti‐SSA/Ro52 antibodies” (9/21, 43%). Notably, six centers (29%) considered either positive anti‐Ro60 or anti‐Ro52 antibodies as positive anti‐SSA antibodies, all of which adopted the latter reporting system. Conclusion Significant variabilities existed among anti‐SSA/Ro assays. Nearly 30% of centers misinterpreted the definition of positive anti‐SSA antibodies, which may be attributed to the confusing reporting systems of line immunoassay. Therefore, we advocate standardization of the nomenclature of anti‐SSA/Ro antibodies, changing the “anti‐SSA/Ro52” label in favor of the “anti‐Ro52” antibodies for a clear designation., Significant variabilities existed among anti‐SSA/Ro assays, with LIA as the most common used method. Nearly one‐third of the centers misinterpreted the definition of positive anti‐SSA antibodies, which may be attributed to the confusing reporting systems of LIA. We advocate changing the “anti‐SSA/Ro52” label in favor of “anti‐Ro52 antibodies” for a clear designation

ObjectiveThis study aims to explore the value of magnetic resonance imaging (MRI) and texture analysis (TA) in the differential diagnosis of ovarian granulosa cell tumors (OGCTs) and thecoma-fibrothecoma (OTCA–FTCA).MethodsThe preoperative MRI data of 32 patients with OTCA–FTCA and 14 patients with OGCTs, confirmed by pathological examination between June 2013 and August 2020, were retrospectively analyzed. The texture data of three-dimensional MRI scans based on T2-weighted imaging and clinical and conventional MRI features were analyzed and compared between tumor types. The Mann–Whitney U-test, χ2 test/Fisher exact test, and multivariate logistic regression analysis were used to identify differences between the OTCA–FTCA and OGCTs groups. A regression model was established by using binary logistic regression analysis, and receiver operating characteristic curve analysis was carried out to evaluate diagnostic efficiency.ResultsA multivariate analysis of the imaging-based features combined with TA revealed that intratumoral hemorrhage (OR = 0.037), log-sigma-20mm-3D_glszm_SmallAreaEmphasis (OR = 4.40), and log-sigma-2-0mm-3D_glszm_SmallAreaHighGrayLevelEmphasis (OR = 1.034) were independent features for discriminating between OGCTs and OTCA–FTCA (P < 0.05). An imaging-based diagnosis model, TA-based model, and combination model were established. The areas under the curve of the three models in predicting OGCTs and OTCA–FTCA were 0.935, 0.944, and 0.969, respectively; the sensitivities were 93.75, 93.75, and 96.87%, respectively; and the specificities were 85.71, 92.86, and 92.86%, respectively. The DeLong test indicated that the combination model had the highest predictive efficiency (P < 0.05), with no significant difference among the three models in differentiating between OGCTs and OTCA–FTCA (P > 0.05).ConclusionsCompared with OTCA–FTCA, intratumoral hemorrhage may be characteristic MR imaging features with OGCTs. Texture features can reflect the microheterogeneity of OGCTs and OTCA–FTCA. MRI signs and texture features can help differentiate between OGCTs and OTCA–FTCA and provide a more comprehensive and accurate basis for clinical treatment.

Aims PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2‐related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain. We aim to evaluate the clinical significance of PRRT2 missense variants by performing in vitro experiments. Methods We systematically reviewed PRRT2‐related disorders and summarized reported PRRT2 missense variants. Protein expression and subcellular localization of mutant PRRT2 were investigated in mammal cells. American College of Medical Genetics and Genomics (ACMG) guidelines were used to analyze the pathogenicity of PRRT2 missense variants. Results A total of 29 PRRT2 missense variants were identified in PRRT2‐related disorders. Ten variants were observed to affect both subcellular localization and protein level, three variants only affect membrane localization, and two variants only affect protein level. According to ACMG guidelines, 15 variants were finally classified as “likely pathogenic”, three as “benign”, three as “likely benign”, and eight as “uncertain significance” variants. The likely pathogenic variants were concentrated in the C‐terminal of PRRT2. Conclusions The pathogenicity of eight uncertain significance variants needs further investigation. C‐terminal of PRRT2 is crucial for its physiological function.

To safely and effectively transfer NH

Dioxins are environmental contaminants that are toxic to humans. The conventional analytical method for dioxins, gas chromatography - high resolution mass spectrometry, is extremely time-consuming and expensive. Research is needed to find alternative methods that will increase sample throughput while decreasing time and costs associated with dioxin detection. Dioxins readily accumulate in fish tissue and fish are a common food source for humans. Thus, the goal of this research was to develop a screening technique for dioxins in fish samples using enzyme-linked immunosorbent assay (ELISA). Three approaches, each with a different fish sample purification method but all using ELISA detection, were undertaken. This research concluded that the approach of Florisil cleanup followed by ELISA detection (Florisil-ELISA) was suitable as a screening technique. The other two approaches, one using gel permeation chromatography (GPC-ELISA) and the other using acid silica and carbon columns (acid silica/carbon-ELISA) for fish sample cleanup, were not suitable.

Background and ObjectivesIsolated paroxysmal kinesigenic dyskinesia (PKD) is mainly caused by PRRT2 variants and TMEM151A variants. Patients with proximal 16p11.2 microdeletion (16p11.2MD) (including PRRT2) often have neurodevelopmental phenotypes, whereas a few patients have PKD. Here, we aimed to identify 16p11.2MD in patients with PKD and describe the related phenotypes.MethodsWhole-exome sequencing and bioinformatics analysis of copy number variant (CNV) were performed in patients with PKD carrying neither PRRT2 nor TMEM151A variant. Quantitative PCR and low-coverage whole-genome sequencing verified the CNV.ResultsWe identified 9 sporadic patients with PKD and 16p11.2MD (∼535 kb), accounting for 9.6% (9/94) of our patients. Together with 9 previously reported patients with PKD and 16p11.2MD, we found that 16p11.2MD was de novo in 11 of 12 tested patients and inherited from a parent in the other patient. And 80% (12/15) of these patients had a mild language delay, 64.3% (9/14) had compromised learning ability, 42.9% (6/14) had a mild motor delay, and 50% (6/12) had abnormal neuroimaging findings. No severe autism disorders were observed.DiscussionMild developmental problems may be overlooked. A detailed inquiry of developmental history and CNV testing are necessary to distinguish patients with 16p11.2MD from isolated PKD.

Dermatomyositis occurs extremely rarely during pregnancy. A number of studies in the published literature have documented how the outcome of pregnancy is poor for both mother and fetus. The present case study reports on a patient who was diagnosed with clinically amyopathic dermatomyositis complicated by interstitial lung disease during pregnancy, and was successfully treated with a combined immunosuppressant regimen. To the best of the authors’ knowledge, this is the first case study detailing how a pregnant woman with clinically amyopathic dermatomyositis with positive anti-melanoma differentiation-associated gene 5 antibody achieved complete remission after early intervention of combined immunosuppressive therapy without residual pulmonary interstitial changes.

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS: Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.

Thrombotic events are the most frequent causes of death in patients with antiphospholipid syndrome (APS). Previous studies have reported infection to be the most important trigger of thrombosis in APS, with molecular mimicry considered to be a major mechanism. Although timely management of infections has been recommended in patients with high suspicion of infection, anti-infective therapy would not take effect in a short time due to the dilemma in determining the origins of infection, especially in patients undergoing immunosuppressive therapy. Here, we describe a 26-year-old patient with systemic lupus erythematosus with triple antiphospholipid antibody positivity who had a stroke involving her dorsolateral medulla, despite timely anti-infective treatment within the context of skin infection caused by Stenotrophomonas maltophilia. To the best of our knowledge, it is the first report about the association between Stenotrophomonas maltophilia infection and thrombotic complications in APS. Thus, solely focusing on anti-infective therapy by the current recommendation for the management of APS may be insufficient within the context of infection; early initiation of effective anticoagulation should also be suggested until the anti-infective therapy becomes effective, especially in patients with high-risk antiphospholipid antibody profiles, in whom the potential benefit would outweigh the risk of bleeding.

Background The aim of this study was to report aseptic, erosive polyarthritis in a patient with common variable immunodeficiency (CVID), which is quite different from the vastly more common nonerosive form. Material/Methods Peripheral blood mononuclear cells of the patient were isolated. Flow cytometry was used to analyze the proportion and function of lymphocytes. A Parker-Pearson needle biopsy was performed on the right knee. Four of her unaffected family members were enrolled as controls. Results A 21-year-old woman was admitted for recurrent polyarthritis of 3-year duration. The right knee, hip, wrist, proximal interphalangeal joints, and left elbow were involved, with progressive joint destruction. She was diagnosed as having CVID based on her recurrent infections, poor response to vaccines, and marked hypogammaglobulinemia. No bacterium or mycobacterium was detected in synovium or synovial fluid. The synovium was infiltrated by lymphocytes rather than neutrophils. Polyarthritis did not resolve by adequate intravenous immunoglobulin substitution and empirical antibiotic treatment, but resolved gradually after treatment with methylprednisolone and tacrolimus, supporting the diagnosis of aseptic polyarthritis. Further analyses showed that although only 0.5% of residual B lymphocytes were existent in peripheral blood of the patient, expressions of activation marker CD69 and production of IL-1β, IL-6, and TNF-α were high. Marked infiltration with CD19+B lymphocytes (as well as CD4+ or CD8+ T lymphocytes) was detected in the synovium. The proportion of IL21+CD4+Th cells from peripheral blood of the patient was high. CD4+ Th cells from the patient secreted nearly 3 times more IL-21 than the same cell type analyzed from unaffected family members, perhaps due to excessive compensation to assist the function of residual B lymphocytes. Conclusions A novel hypothesis in CVID concurrent with aseptic, erosive polyarthritis is that excessive activation of residual B lymphocytes infiltrate into the synovium of the involved joints and lead to polyarthritis and joint destruction.

To investigate the value of MRI-based features and texture analysis (TA) in the differential diagnosis between ovarian thecomas/fibrothecomas (OTCA/f-TCAs) and uterine fibroids in the adnexal area (UF-iaas).This retrospective study included 16 OTCA/f-TCA and 37 UF-iaa patients who underwent conventional MRI and DWI between August 2014 and September 2018. Three-dimensional TA was performed with T2-weighted MRI. The clinical, MRI-based and texture features were compared between OTCA/f-TCAs and UF-iaas. Multivariate logistic regression analysis was used for filtering the independent discriminative features and constructing the discriminating model. ROCs were generated to analyse MRI-based features, texture features and their combination for discriminating between the two diseases.Six imaging-based features (ipsilateral ovary detection, arterial period enhancement, lesion components, peripheral cysts, "whorl signs", mean ADCs) and six texture features (Histogram-energy, Histogram-entropy, Histogram-kurtosis, GLCM-energy, GLCM-entropy, and Haralick correlation) were significantly different between OTCA/f-TCAs and UF-iaas (p0.05). Multivariate analysis of the MRI-based features revealed that arterial period enhancement (OR = 0.104), peripheral cysts (OR = 16.513), and whorl signs (OR = 0.029) were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p0.05). Multivariate analysis of the texture features showed that Histogram-energy and GLCM-energy were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p0.05). The area under the curve of imaging-based diagnosis was 0.85, and the combination of imaging-based diagnosis and TA improved the area under the curve to 0.87, with higher accuracy, specificity and sensitivity of 86%, 92%, and 84%, respectively (p0.05).MRI-based features can be useful in differentiating OTCA/f-TCAs from UF-iaas. Furthermore, combining imaging-based diagnosis and TA can improve diagnostic performance.

Genetic factors are considered to play a critical role in patients with early-onset Parkinson’s disease (EOPD). The genetic spectrum of EOPD patients has been extensively investigated in Caucasian populations but rarely in the Chinese population. In this study, a total of 21 unrelated Chinese EOPD patients were enrolled. Multiplex ligation-dependent probe amplification assay and whole-exome sequencing were performed, followed by Sanger sequencing. Detailed clinical features were presented. Two novel likely pathogenic variants (p.Q648X in ATP13A2 and p.N521fs in PINK1) and 10 previously reported Parkin pathogenic variations (exon 2 deletion, exon 3–4 deletion, exon 4 deletion, exon 6–7 deletion, exon 7 deletion; p.G284R, p.G329 V, p.R366W, p.N428fs, p.M458 L) were identified in 9 out of 21 (42.86%) patients. The frequency (33.33%) of Parkin variations is much higher in our cohort than that in the East Asian population. The patient carrying the ATP13A2 variant showed no response to levodopa treatment. Our findings broaden the genetic spectrum and clinical features of EOPD patients.

OBJECTIVE: To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis (PNAC) in preterm infants. METHODS: Among the preterm infants who were admitted to the hospital from June 2011 to November 2017 and received parenteral nutrition for more than 14 days, 80 who did not develop PNAC were enrolled as non-PNAC group, and 76 who developed PNAC were enrolled as PNAC group. On days 1, 14, 30, 60 and 90 after birth, serum hepatobiliary biochemical parameters[alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT)], fibrosis indices[hyaluronic acid, laminin, procollagen Ⅲ N-terminal peptide and type IV collagen] and clinical manifestations were observed. Real-time quantitative PCR was used to measure the mRNA expression of MDR3 in both groups, and the correlation between the mRNA expression of MDR3 and serum hepatobiliary biochemical parameters was analyzed. RESULTS: In the PNAC group, serum levels of hepatobiliary biochemical parameters and fibrosis indices increased on day 14 after birth and reached the peak on day 30 after birth, followed by a reduction on day 60 after birth. On days 14, 30, 60 and 90 after birth, the PNAC group had significantly higher serum levels of hepatobiliary biochemical parameters and fibrosis indices than the non-PNAC group (P < 0.05). The PNAC group had higher relative mRNA expression of MDR3 in peripheral blood cells than the non-PNAC group (P < 0.05). In the PNAC group, the relative mRNA expression of MDR3 in peripheral blood cells was negatively correlated with serum levels of hepatobiliary biochemical parameters (ALT, TBil, DBil, TBA and γ-GT) (P < 0.001). CONCLUSIONS: High mRNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.

BackgroundMagnetic resonance imaging (MRI) is a significant method of identifying ovarian tumors, when combined with certain functional imaging techniques that have been considered to be mo...

The Psychoeducational Profile-Third Edition (PEP-3), a standardized and norm-referenced scale, is designed to assess the development of communication and motor skills and the presence of maladaptive behaviors in children with autism spectrum disorder (ASD). The purpose of this study was to develop a short form of the PEP-3, the SF-PEP3, which would reduce the administration time while maintaining the psychometric properties similar to the original version. The study consisted of two parts: development and cross-validation of the SF-PEP3. In the first part, 116 children with ASD were recruited and assessed with the Chinese Psychoeducational Profile-Third Edition (CPEP-3). After 6 months, 63 of them were assessed again. We developed the SF-PEP3 by selecting the items with the highest internal consistency and the greatest responsiveness. The easiest and the most difficult items were added because of the notable ceiling and floor effects. The psychometric properties of the 4 versions of the SF-PEP3 were compared with the original CPEP-3. The score distribution, the reliability, and the concurrent validity of the 73-item SF-PEP3 were better than those of the 57-item and 66-item SF-PEP3s. The responsiveness of the 73-item SF-PEP3 was better than those of the 79-item SF-PEP3 and the original CPEP-3. Thus, the 73-item SF-PEP3 was determined to be the best. In the second part, 101 children with ASD were recruited, and 35 of them were followed up after 1 year. The psychometric properties of the 73-item SF-PEP3 were cross-validated and found to be similar to those of the original CPEP-3. In conclusion, the 73-item SF-PEP3 has been developed and shown to be psychometrically similar to the original CPEP-3. It is recommended that the 172-item CPEP-3 be used in the initial evaluation and that the subtests or composites scores of the 73-item SF-PEP3 be used as the outcome indicators for children with ASD.

BackgroundAutoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse. Here, we aimed to evaluate the incidence of TAbs in a consecutive Chinese RA cohort and to investigate whether the elevated presence of TAbs is associated with joint damage and synovitis in RA patients.MethodsA total of 125 hospitalized RA patients were consecutively recruited. Clinical data and available synovial tissues were collected at baseline, and TAbs and thyroid function were detected by chemiluminescent immunoassay. Patients who tested positive for TPOAbs or TgAbs were classified as the TAbs-positive group, and patients who tested positive for neither TPOAbs nor TgAbs were recruited as the TAbs-negative group. Disease activity was assessed using DAS28-ESR (the disease activity score in 28 joints and including the erythrocyte sedimentation rate). X-ray assessment of the hand/wrist was performed according to the Sharp/van der Heijde-modified Sharp score (mTSS), and patients with an mTSS score >10 were defined as having radiographic joint damage (RJD). Serial tissue sections were stained immunohistochemically for CD3, CD15, CD20, CD34, CD38, and CD68, and synovitis were assessed according to Krenn’s synovitis score.ResultsA total of 44 (35%) patients were positive for either TPOAbs or TgAbs. Importantly, there was a significantly greater percentage of patients with RJD in the TAbs-positive group versus the TAbs-negative group (68% vs. 42%,p = 0.005). Compared with the TAbs-negative group, significantly more CD38-positive plasma cells infiltrated the TAbs-positive synovium, and a higher percentage of patients with high-grade synovitis were observed in the TAbs-positive group (5/8, 63% vs. 5/14, 36%). Moreover, RF positivity and disease activity indicators, including TJC28, DAS28-ESR, and CDAI, were significantly higher in the TAbs-positive group (allp p = 0.010) and disease duration (OR 1.013, 95% CI [1.006–1.019];p n = 37) compared with those without TAbs (n = 59) (p = 0.038).ConclusionOur data showed that joint destruction was amplified in RA patients with an elevated presence of TAbs, which supports the importance and necessity of TAbs and thyroid function screening and monitoring in RA patient management in clinical practice.

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients who undergo immunosuppressive drug therapy. Although the recommendation of antiviral prophylaxis made by the American Gastroenterological Association in 2015 focuses on the risk stratification of different immunosuppressive drugs, risk factors for HBV reactivation are also worth identifying in clinical practice. Recent studies have shown that the uncommon serological pattern of coexistent circulating HBV surface antigen (HBsAg) and its antibody (anti-HBs) was associated with double mutations (A1762T/G1764A) in the basal core promoter (BCP) region of the HBV genome, which is critical for HBV replication. Here, we depicted rheumatoid arthritis (RA) patients with coexistent HBsAg and anti-HBs in our medical center, who developed HBV reactivation during immunosuppressive drug therapy. DNA sequencing analysis of the HBV genome revealed triple mutations (A1762T, G1764A, and T1753V) in the BCP region, which could further enhance the ability of HBV replication. Hence, a novel hypothesis is advanced for the first time that patients with coexistent HBsAg and anti-HBs may have a strong predisposition to HBV reactivation due to specific BCP mutations. This hypothesis would, if correct, justify the concurrent detection of HBsAg and anti-HBs in HBV screening in patients with rheumatic diseases and quickly recognize patients with high risk of HBV reactivation. Further controlled studies are needed to confirm this hypothesis.