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Background: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc)., Objective: A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China., Methods: Patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs., Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% of patients were negative. There were more males among ANA-negative SSc patients (29/60 vs. 294/1746, p < 0.001). The incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs. 18.5%, p = 0.002), interstitial lung disease (65.2% vs. 77.9%, p = 0.015), and pulmonary arterial hypertension (11.5% vs. 29.0%, p = 0.006) was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal erythrocyte sedimentation rate (32.4% vs. 47.6%, p = 0.013) and IgG elevation (14.3% vs. 37.0%, p = 0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients., Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: CRa is a key gene in Chinese cabbage (Brassica rapa ssp. pekinensis) that confers resistance to Plasmodiophora brassicae. In order to efficiently screen the clubroot resistance (CR) gene CRa in breeding, two functional codominant markers of the CRa gene were developed., Methods and Results: In this study, through comparing the CRa allele sequences in resistant and susceptible cultivars of Chinese cabbage, we found two insertion and deletion of sequence variations in the fourth exon between resistant and susceptible cultivars. Two functional codominant markers for CRa gene were obtained based on the variations, namely, CRaEX04-1 and CRaEX04-3. The lengths of the extended fragment of CRaEX04-1 marker were 321 bp and 186 bp in resistant and susceptible cultivars, respectively. In contrast, those of CRaEX04-3 were 704 bp and 413 bp, respectively. We verified the genetic stability between the developed markers and CRa gene using 57 Chinese cabbage cultivars with known resistance and two genetic populations. The results showed that the marker identification was completely consistent with the known phenotypes in 57 cultivars. The marker identification results followed the 3:1 of Mendel's first law in the F 2 population, and the 1:1 of Mendel's first law in the BC 1 ., Conclusions: CRaEX04-1 and CRaEX04-3 can be used as a practical molecular marker for breeding and germplasm resource creation of clubroot disease-resistant Chinese cabbage., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Left ventricular diastolic dysfunction (LVDD) is a common manifestation of cardiac involvement in systemic sclerosis (SSc), which is associated with increased mortality, but little is known about the risk factors. The aim is to determine the frequency and potential predictors of SSc-LVDD., Methods: We conducted a prospective multi-center cohort study, enrolling 784 SSc patients assessed by echocardiography between April 2008 and June 2019. Diagnosis of systemic sclerosis was according to the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria. Data were compared between patients with and without LVDD, while univariate and multivariate regression analysis was performed to determine the factors independently associated with LVDD., Results: LV diastolic dysfunction was present in 246/784 (31.4%) of the subjects. There were no significant differences in gender, BMI, or disease duration between the two groups. Around 40% of the patients in the SSc-LVDD group and in the SSc-non LVDD group had diffused cutaneous involvements. Factors independently associated with LV diastolic dysfunction in multivariable analysis included age at onset (OR 1.053, 95%CI 1.021-1.086, p = 0.001), pulmonary arterial hypertension (OR 3.057, 95%CI 1.468-6.367, p = 0.003), positivity of anti-RNP antibody (OR 2.455, 95%CI 1.049-5.745, p = 0.038), increased WBC count (OR 1.156, 95%CI 1.037-1.287, p = 0.009), elevated levels of uric acid (OR 1.003, 95%CI 1.000-1.006, p = 0.036), and triglyceride (OR 1.515, 95%CI 1.106-2.077, p = 0.010)., Conclusion: LV diastolic dysfunction was prevalent in the SSc population. Advanced onset age, PAH, positive anti-RNP antibody, increased WBC count, and adverse metabolic status were independent risk factors for SSc-related LVDD. Key Points • In this Chinese multi-center cohort of systemic sclerosis, LVDD is not a rare complication, with a prevalence of 31.4%. • The presence of advanced onset age, PAH, positive anti-RNP antibody, increased WBC count and adverse metabolic status were baseline predictors of developing LVDD in SSc., (© 2021. International League of Associations for Rheumatology (ILAR).)

Forsythiae suspensa is widely used in China as a traditional Chinese medicine. Forsythin is extracted from Forsythiae Fructus and has undergone phase II clinical trials as an antipyretic drug in China. The main metabolites of forsythin in human plasma are aglycone sulfate (KD-2-SO 3 H) and aglycone glucuronide (KD-2-Glc). In the present study, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the simultaneous analysis of forsythin, KD-2-Glc, and KD-2-SO 3 H, in human plasma. After precipitating proteins with methanol, these three analytes were separated on a Gemini-C18 column along with teniposide as an internal standard. Mass spectrometry detection, under multiple reaction monitoring, was then carried out in negative mode using the Triple Quad™ 6500 + LC-MS/MS system coupled with an electrospray ionization (ESI) ion source. The transitions of m/z 371.1→356.1 for forsythin, m/z 547.2→356.0 for KD-2-Glc and m/z 451.2→356.2 for KD-2-SO 3 H were chosen to effectively maintain the balance between selectivity and sensitivity. The developed method was linear over the following concentrations in human plasma samples: 1.00-1000 ng/mL for forsythin, 2.50-2500 ng/mL for KD-2-Glc, and 5.00-5000 ng/mL for KD-2-SO 3 H. Assays were validated and satisfied the acceptance criteria recommended by the CFDA guidance. Furthermore, this LC-MS/MS method was successfully implemented in a Phase I, first-in-human, dose-escalation pharmacokinetic study among Chinese healthy participants after single oral administration of forsythin tablets., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Fusobacteria are not common nor relatively abundant in non-colorectal cancer (CRC) populations, however, we identified multiple Fusobacterium taxa nearly absent in western and rural populations to be comparatively more prevalent and relatively abundant in southern Chinese populations. We investigated whether these represented known or novel lineages in the Fusobacterium genus, and assessed their genomes for features implicated in development of cancer., Methods: Prevalence and relative abundances of fusobacterial species were calculated from 3157 CRC and non-CRC gut metagenomes representing 16 populations from various biogeographies. Microbial genomes were assembled and compared with existing reference genomes to assess novel fusobacterial diversity. Phylogenetic distribution of virulence genes implicated in CRC was investigated., Results: Irrespective of CRC disease status, southern Chinese populations harboured increased prevalence (maximum 39% vs 7%) and relative abundances (average 0.4% vs 0.04% of gut community) of multiple recognised and novel fusobacterial taxa phylogenetically distinct from Fusobacterium nucleatum . Genomes assembled from southern Chinese gut metagenomes increased existing fusobacterial diversity by 14.3%. Homologues of the FadA adhesin linked to CRC were consistently detected in several monophyletic lineages sister to and inclusive of F. varium and F. ulcerans , but not F. mortiferum . We also detected increased prevalence and relative abundances of F. varium in CRC compared with non-CRC cohorts, which together with distribution of FadA homologues supports a possible association with gut disease., Conclusion: The proportion of fusobacteria in guts of southern Chinese populations are higher compared with several western and rural populations in line with the notion of environment/biogeography driving human gut microbiome composition. Several non-nucleatum taxa possess FadA homologues and were enriched in CRC cohorts; whether this imposes a risk in developing CRC and other gut diseases deserves further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulmonary arterial hypertension (PAH) is a severe complication and leading cause of mortality in patients with primary Sjogren's syndrome (pSS). This study was to investigate the overall survival rates and the utility of red blood cell distribution width (RDW) as a potential prognostic factor of pSS-PAH. This cohort study retrospectively enrolled 55 patients with pSS-PAH who were followed up at the Department of Rheumatology of Peking Union Medical College Hospital (PUMCH) between August 2007 and May 2017. The patients were stratified according to the level of RDW (≤ 15.0 and > 15.0%). Baseline demographics, laboratory results, pulmonary function conditions, hemodynamic assessments, and treatment regimens were analyzed. Cox proportional hazards regression analysis was used to identify whether RDW level is a factor related to adverse outcome. A total of 55 patients were recruited, with an average age of 38.9 ± 9.3 years. Fifty-four were female (98.2%), and the average duration at the time of PAH diagnosis was 25.5 ± 33.2 months. Higher RDW levels were found in patients who deceased in follow-up (13.8 ± 2.6 vs 16.5 ± 1.6%, p = 0.003) and with higher NYHA classes (13.8 ± 1.8 vs 16.5 ± 2.9%, p < 0.001). Patients with RDW > 15% had a significantly worse overall survival than patients with RDW ≤ 15% (3-year survival rate 59.5 vs. 88.7% log-rank p = 0.015). Cox regression analysis identified RDW > 15% as a prognostic factor for adverse outcome (HR 1.786, 95% CI 1.137-2.803, p = 0.012). RDW can serve as a potential negative prognostic factor of pSS-PAH.

Diagnosis of active tuberculosis (TB) in children remains difficult. This study aimed at evaluating the ability of interferon-gamma release assays (IGRAs) in the detection of active TB in human immunodeficiency virus-negative children vaccinated with Bacille Calmette-Guérin and investigating the effect of prednisolone treatment on the IGRAs performance. Among the 162 children with suspected TB disease recruited in China, 60 were tested with QuantiFERON-TB Gold In Tube (QFT-GIT) and 102 were tested with T-SPOT.TB. QFT-GIT presented a sensitivity of 83.9 % (95 % CI 66.9-93.4 %) and a specificity of 88.5 % (95 % CI 70.2-96.8 %), while T-SPOT.TB had a sensitivity of 75.9 % (95 % CI 63.4-85.2 %) and a specificity of 94.7 % (95 % CI 81.8-99.5 %). The positive predictive value was high in both assays, 92.9 % for QFT-GIT and 95.7 % for T-SPOT.TB. In total of these two kinds of IGRAs, false negative rate was significantly higher in children receiving systemic prednisolone (1 mg/kg/day) therapy for >1 week (two tested with T-SPOT.TB and five tested with QFT-GIT) than in those with ≤1 week of prednisolone therapy and without prednisolone therapy (57.1 vs. 18.3 %, p = 0.035). There was no significant difference of the positive rate of both tests in children <5 years old compared with those ≥5 years old. Both types of IGRAs showed good diagnostic values in detecting childhood TB before microbiological evidence was available. Glucocorticoids had a significant negative influence on IGRAs if treated for >1 week. Age made no difference on the performance of these tests in children.

Objective: Using methodology of molecular genetics to explore the origin, phylogen, and gene flow of Mycobacterium tuberculosis (MTB) Beijing lineage in the five provinces from northern China, including Heilongjiang, Jilin, Liaoning, Neimenggu and Ningxia., Methods: 234 MTB Beijing lineage strains were genotyped by 24 Variable Number Tandem Repeat (VNTR), and the h (the allelic diversity) value of each VNTR locus was calculated. On individual level of phylogeny, it was constructed Neighbor-Joining (N-J) tree and minimum spanning tree (MST). Phylogenetic tree was built at the population level, and the most recent common ancestor (TMRCA) was estimated through Bayesian model. Molecular variance (AMOVA) was used to understand the gene flow among strains discovered from the five provinces., Results: Allelic diversities of the 24 VNTR loci were low (h: 0.000 - 0.744). 234 strains of MTB Beijing lineage were dispersed in individual branch of the N-J tree, with 62.0% (145) of them grouped to the same "colonial complexes" in MST. At the population level, the evolution relationship of 234 strains appeared the closest to Beijing lineage, which was from MIRU-VNTRplus database, and the bootstrap was 100. The TMRCA was 5308 (95%CI: 4263 - 6470) years. Differences of pairwise Fst values acquired by AMOVA between Jilin and Heilongjiang, Liaoning, Neimenggu and Ningxia, were not statistically significant (P > 0.05)., Conclusion: The genetic similarity of Beijing lineage MTB from the five provinces of northern China was high. The phylogeny branches had no characteristic dispersal in each province. It was speculated that these strains showed an evolution from a clone of MTB Beijing lineage (about 5000 years ago). The gene flow was taking place between neighboring zones.

This study employed culture and polymerase chain reaction (PCR) to examine the prevalence of Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Mycoplasma fermentans, Mycoplasma penetrans and Mycoplasma pirum in 210 HIV/AIDS patients, 455 sexually transmitted infection (STI) clinic attendees and 245 healthy volunteers from first-void urine specimens for men and endocervical swabs for women. U. urealyticum and M. hominis were detected in 107 (51.0%) and 69 (32.9%) patients in the HIV/AIDS group. At least one of the other four organisms was detected in 34 (16.2%) HIV/AIDS patients, 29 (6.4%) STI clinic attendees and six (2.5%) healthy volunteers. This study showed that U. urealyticum, M. hominis and M. fermentans were significantly more prevalent in HIV/AIDS patients, as were other mycoplasmas. Our results suggest a possible role for co-infection.

The essential oils from leaves, twigs and stems of large trees and shrub-like trees of Thuja sutchuenensis were extracted by hydrodistillation and supercritical fluid extraction, and analyzed by GC and GC-MS. The essential oil composition differed significantly among the three organs, as well as between large trees and shrub-like trees. Furthermore, consistent with the eastern Asia-North American disjunct distribution of the genus, many differences in the essential oil composition between T. sutchuenensis and other Thuja species were apparent. The essential oils exhibited a certain degree of antifungal activity against six strains of human pathogenic fungi.

Marine scallops, with extended planktonic larval stages which can potentially disperse over large distances when advected by marine currents, are expected to possess low geographical differentiation. However, the sessile lifestyle as adult tends to form discrete "sea beds" with unique population dynamics and structure. The narrow distribution of Zhikong scallop (Chlamys farreri), its long planktonic larval stage, and the extremely hydrographic complexity in its distribution range provide an interesting case to elucidate the impact of marine currents on geographical differentiation for marine bivalves at a fine geographical scale. In this study, we analyzed genetic variation at nine microsatellite DNA loci in six locations throughout the distribution of Zhikong scallop in the Northern China. Very high genetic diversity was present in all six populations. Two populations sampled from the same marine gyre had no detectable genetic differentiation (F (ST) = 0.0013); however, the remaining four populations collected from different marine gyres or separated by strong marine currents showed low but significant genetic differentiation (F (ST) range 0.0184-0.0602). Genetic differentiation was further analyzed using the Monmonier algorithm to identify genetic barriers and using the assignment test conducted by software GeneClass2 to ascertain population membership of individuals. The genetic barriers fitting the orientation of marine gyres/currents were clearly identified, and the individual assignment analysis indicated that 95.6% of specimens were correctly allocated to one of the six populations sampled. The results support the hypothesis that significant population structure is present in Zhikong scallop at a fine geographical scale, and marine currents can be responsible for the genetic differentiation.

In this study, the phenotypic and genotypic resistance to fluoroquinolones in Neisseria gonorrhoeae isolated in Jiangsu Province, China, was analysed. In vitro susceptibility testing of eight antimicrobial agents, including ciprofloxacin and levofloxacin, against 95 clinical isolates was carried out. Detection of mutations in the gyrA and parC genes was performed by sequence analysis. The clinical isolates demonstrated 100% resistance to ciprofloxacin and 98.9% non-susceptibility to levofloxacin. All of the isolates were susceptible to cefotaxime and ceftriaxone. For cefepime, spectinomycin and tetracycline, 98.9, 94.7 and 1.1% of the isolates were susceptible, respectively. None of the isolates was susceptible to penicillin. Five types based on gyrA mutations could be categorized among 54 isolates with seven different mutation sites found on their parC gene. Analysis of sequence results showed that the gyrA mutation Asp-95-->Ala and the parC mutations Ser-87-->Arg and Ser-87-->Asn made a significant contribution to the resistance to fluoroquinolones, in addition to double mutations found in each gene. Therefore, the use of fluoroquinolones in the treatment of N. gonorrhoeae infections in Jiangsu Province is not recommended, while the use of third- and fourth-generation cephalosporins and spectinomycin is recommended.