Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

Sex-Specific Effects of Polystyrene Microplastic and Lead(II) Co-Exposure on the Gut Microbiome and Fecal Metabolome in C57BL/6 Mice.

The wide spread of microplastics has fueled growing public health concern globally. Due to their porous structure and large surface area, microplastics can serve as carriers for other environmental pollutants, including heavy metals. Although the toxic effects of microplastics or heavy metals have been reported previously, investigations into the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In the present study, the effects of polystyrene microplastics and lead(II) co-exposure on the gut microbiome, intestinal permeability, and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead(II) increased intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. In particular, Shannon and Simpson indices of gut bacteria were reduced by the co-exposure only in female mice. A total of 34 and 13 fecal metabolites were altered in the co-exposure group in female and male mice, respectively, among which only three metabolites were shared by both sexes. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.

Clinical features and prognosis of systemic lupus erythematosus complicated by active cytomegalovirus infection: a retrospective cohort study.

Objective: The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection. Methods: This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months. Results: A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months. Conclusion: In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.

Incidence and Risk Factors of Active Tuberculosis Among Hospitalized Patients with Latent Tuberculosis Infection in China: A Cohort Study.

Background: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients. Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.

Multi-component analyses of raspberry: Optimization of extraction procedure and network pharmacology.

The contents of ellagic acid and kaempferol-3-O-rutinoside, the chief active components of raspberry, are considered the quality control indices of raspberry. This work employed the ant colony neural network (ACO-BPNN) to optimize their extraction processes, and the combination of network pharmacology and molecular docking technology to unveil the potential pharmacological effects of these components. Based on the single-factor test (ultrasonic time, ethanol concentration, ultrasonic temperature, and solid-liquid ratio), a factorial experiment with 4-factors and 3-levels was conducted in parallel for 3 times. The multi-factor analysis of variance results revealed high-order interactions among the factors. Then, the ACO-BPNN model was established to characterize the complex relationship of experimental data. After further verification, relative errors were all less than 8 %, implying the model's effectiveness and reliability. Moreover, with the network pharmacology, 66 key targets were screened out and mainly concentrated in PI3K-AKT, MAPK, and Ras signal pathways. Molecular docking revealed the binding sites between active components and key targets.

Incidence and risk factors of tuberculosis in systemic lupus erythematosus patients: a multi-center prospective cohort study.

Objectives: Both burdens of tuberculosis (TB) and systemic lupus erythematosus (SLE) in China are ranked as top three in the world. SLE patients are at high risk for TB, but so far, there are no guidelines for TB prevention and management targeting this population in China. This study aims to investigate the incidence of active tuberculosis (ATB) and to explore the risk factors for developing ATB in SLE patients, and to provide evidence for TB prevention and management for SLE patients in China. Methods: A multi-center prospective cohort study was conducted. SLE patients were enrolled from clinics and wards of 13 tertiary hospitals in Eastern, Middle, and Western China from September 2014 to March 2016. Baseline demographic features, TB infection status, clinical information, and laboratory data were collected. ATB development was examined during follow-up visits. Kaplan-Meier method was applied to plot survival curves, and Log-rank test was used to evaluate differences. Cox proportional-hazards model was used to explore the risk factors for ATB development. Results: With a median follow-up time of 58 months [interquartile range (IQR): 55-62], 16 out of 1361 SLE patients developed ATB. The 1-year incidence of ATB was 368 [95% confidence interval (CI): 46-691] per 100,000. Over a 5-year period, the cumulative incidence of ATB was 1141 [95% CI: 564-1718] per 100,000, and the incidence density was 245 per 100,000 person-years. Cox regression models were constructed with maximum daily dose of glucocorticoids (GCs) as a continuous variable and a categorical variable, respectively. In model 1, maximum daily dose of GCs (pills per day) [adjusted hazard ratio (aHR)=1.16, 95%CI: 1.04-1.30, p=0.010] and TB infection (aHR=8.52, 95%CI: 3.17-22.92, p<0.001) were independent risk factors for ATB development. In model 2, maximum daily dose of GCs≥30 mg/d (aHR =4.81, 95%CI: 1.09-22.21, P=0.038) and TB infection (aHR=8.55, 95%CI: 3.18-23.00, p<0.001] were independent risk factors for ATB development. Conclusions: SLE patients had a higher incidence of ATB compared to the general population. The risk of developing ATB was even higher with increased daily dose of GCs or in a status of TB infection, in which case TB preventive treatment should be considered.

Latent Tuberculosis Infection and Associated Factors in Patients with Systemic Lupus Erythematosus: a Multicenter, Cross-Sectional Study.

The objectives of this study were to screen for latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE) using the T-SPOT.TB assay and to identify factors affecting the assay results. SLE patients were enrolled from 13 tertiary hospitals in eastern, central, and western China from September 2014 to March 2016 and were screened using the T-SPOT.TB assay to detect LTBI. Basic information about the subjects was collected, including gender, age, body mass index (BMI), course of disease, evidence of previous tuberculosis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and the use of glucocorticoids and immunosuppressants. Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of the T-SPOT.TB assay. In all, 2,229 SLE patients were screened using the T-SPOT.TB assay, of whom 334 patients tested positive, yielding a positivity rate of 15% (95% confidence interval [CI], 13.5% to 16.5%). The positivity rate was higher in male than female patients and had an increasing trend with age. Multivariable logistic regression analysis showed that patients over 40 (odds ratio [OR], 1.65; 95% CI, 1.29 to 2.10) and with evidence of previous tuberculosis (OR, 4.43; 95% CI, 2.81 to 6.99) were more likely to have positive T-SPOT.TB results, while patients with a SLEDAI-2K score of ≥10 (OR, 0.61; 95% CI, 0.43 to 0.88), a glucocorticoid dose of ≥60 mg/d (OR, 0.62; 95% CI, 0.39 to 0.98), leflunomide (LEF) treatment (OR, 0.51; 95% CI, 0.29 to 0.88), or tacrolimus (FK506) treatment (OR, 0.40; 95% CI, 0.16 to 1.00) were more likely to have negative T-SPOT.TB results. The frequencies of CFP-10-specific gamma interferon (IFN-γ)-secreting T cells were significantly lower in SLE patients with severe disease activity or high-dose glucocorticoids (P < 0.05). The positivity rate of the T-SPOT.TB assay was 15% among SLE patients. Severe, active SLE disease and the use of high-dose glucocorticoids and some types of immunosuppressants are likely to result in negative T-SPOT.TB results. For SLE patients with the above conditions, diagnosing LTBI based on a positive T-SPOT.TB result may lead to underestimation of the prevalence. IMPORTANCE The burden of tuberculosis and systemic lupus erythematosus in China ranks among the top three in the world. Therefore, active screening for LTBI and preventive intervention in SLE patients are of great significance in China. In view of the lack of relevant data in a large sample, we conducted a multicenter, cross-sectional study using T-SPOT.TB as a screening method for LTBI, to investigate the prevalence of LTBI and analyze the factors affecting the results of the T-SPOT.TB assay in SLE patients. Our study showed that the overall positivity rate of the T-SPOT.TB assay in SLE patients was 15.0%, which was lower than the estimated LTBI prevalence in the general population in China (~20%). For SLE patients with severe, active disease, high-dose glucocorticoids, and some types of immunosuppressants, a diagnosis of LTBI based on only positive T-SPOT.TB results may lead to underestimation of the prevalence.

Size-dependent effects of polystyrene microplastics on gut metagenome and antibiotic resistance in C57BL/6 mice.

Microplastic pollution is an emerging threat for marine and terrestrial ecosystems, which has raised global concerns about its implications for human health. Mounting evidence has shown that the gut microbiota plays a key role in human health and diseases. The gut bacteria could be disturbed by many environmental factors, including the microplastic particles. However, the size effect of polystyrene microplastics on mycobiome, as well as gut functional metagenome has not been well studied. In this study, we performed ITS sequencing to explore the size effect of polystyrene microplastics on the fungal composition, in combination with the shotgun metagenomics sequencing to reveal the size effects of polystyrene on the functional metagenome. We found that polystyrene microplastic particles with 0.05-0.1 µm diameter showed greater impact on the bacterial and fungal composition of gut microbiota as well as the metabolic pathways than the polystyrene microplastic particles with 9-10 µm diameter. Our results suggested that size-depended effects should not be ignored in the health risk assessment of microplastics.

Alterations of gut microbial pathways and virulence factors in hemodialysis patients.

Alterations in gut microbiota might contribute to uremic toxicity and immune dysregulation in patients with end-stage renal disease. Hemodialysis patients are prone to infection and higher mortality following sepsis. The virulence factors in the gut metagenome have not been well studied in hemodialysis patients, which could be employed by microorganisms to successfully thrive and flourish in their hosts. In this study, we performed shotgun metagenomics sequencing on fecal DNA collected from 16 control subjects and 24 hemodialysis patients. Our analysis shows that a number of microbial species, metabolic pathways, antibiotic resistance, and virulence factors were significantly altered in hemodialysis patients compared with controls. In particular, erythromycin resistance methylase, pyridoxamine 5-phosphate oxidase, and streptothricin-acetyl-transferase were significantly increased in hemodialysis patients. The findings in our study laid a valuable foundation to further elucidate the causative role of virulence factors in predisposing HD patients to infection and to develop treatment strategies to reduce the genetic capacities of antibiotic resistance and virulence factors in HD patients.

Clinical Features of Spontaneous Remission in the Classic Fever of Unknown Origin: A Retrospective Study.

Objective To summarize the clinical features of spontaneous remission in classic fever of unknown origin (FUO). Methods Medical records of 121 patients diagnosed with FUO at admission in Peking Union Medical College Hospital between January 2018 and June 2018 were reviewed retrospectively. Patients who were discharged without etiological diagnoses were followed for 2 years. The clinical features and outcomes of these patients were summarized. Multivariate logistic regression was used to analyze related factors of spontaneous remission of FUO. Results After excluding 2 patients who lost to follow-up, the etiology of 119 FUO patients were as follows: infectious diseases in 30 (25.2%) cases, connective tissue diseases in 28 (23.5%) cases, tumor diseases in 8 (6.7%) cases, other diseases in 6 (5.0%) cases, and unknown diagnoses in 47 (39.5%) cases. Totally, 41 patients experienced spontaneous remission of fever (the median time from onset to remission was 9 weeks, ranging from 4 to 39 weeks). In patients with spontaneous remission in FUO, lymphadenopathy was less common clinical manifestation, the levels of inflammatory markers including leukocyte count, neutrophil count, neutrophil ratio, C-reactive protein, and ferritin were lower, and the proportion of CD8 positive T lymphocytes expressing CD38 was lower. Multivariate logistic regression analysis of factors with a P-value < 0.05 in univariate analysis shown that white blood cell count (OR: 0.545, 95%CI: 0.306-0.971, P = 0.039), neutrophil count (OR: 2.074, 95%CI: 1.004-4.284, P = 0.049), and proportion of neutrophils (OR: 0.928, 95%CI: 0.871-0.990, P = 0.022) were independent significant factors associated with spontaneous remission in FUO. Conclusions This study suggested that most patients discharged with undiagnosed classic FUO would remit spontaneously. Thus, for patients with stable clinical conditions, follow-up and observation could be the best choice. Patients with lower level of some inflammatory factors may have a high likelihood of spontaneous remission in classic FUO.

Lipidomics for the Prediction of Progressive Liver Disease in Patients with Alcohol Use Disorder.

Alcohol-related liver disease is a public health care burden globally. Only 10-20% of patients with alcohol use disorder have progressive liver disease. This study aimed to identify lipid biomarkers for the early identification of progressive alcohol-related liver disease, which is a key step for early intervention. We performed untargeted lipidomics analysis in serum and fecal samples for a cohort of 49 subjects, including 17 non-alcoholic controls, 16 patients with non-progressive alcohol-related liver disease, and 16 patients with progressive alcohol-related liver disease. The serum and fecal lipidome profiles in the two patient groups were different from that in the controls. Nine lipid biomarkers were identified that were significantly different between patients with progressive liver disease and patients with non-progressive liver disease in both serum and fecal samples. We further built a random forest model to predict progressive alcohol-related liver disease using nine lipid biomarkers. Fecal lipids performed better (Area Under the Curve, AUC = 0.90) than serum lipids (AUC = 0.79). The lipid biomarkers identified are promising candidates for the early identification of progressive alcohol-related liver disease.

Quality control and product differentiation of LMWHs marketed in China using 1H NMR spectroscopy and chemometric tools.

Low molecular weight heparins (LMWHs) are heterogeneous mixtures of glycosaminoglycan chains composed of mixture of different lengths and substitution patterns. Structural characterization and quality control of LMWHs have always been challenging. The Chinese drug regulatory authorities have been committed to improve the supervision standards of LMWHs to better regulate the quality and safety of LMWHs in current Chinese market. In the present paper, 80 batches of three types LMWHs (dalteparin, enoxaparin and naldroparin) marketed in China from different manufacturers were studied by 1H NMR experiments and chemometric analysis. The method can be used not only to monitor impurities and contaminants, but also to check the batch-to-batch consistency of each manufacture. Moreover, for the biosimilar LMWHs from different manufactures, they can be differentiated and clustered according to their slightly different structural compositions originated from production process. By using this method, the quality and safety of LMWHs marketed in China were initially assessed.

[Clinical Characteristics of 68 Patients with Osteoarticular Tuberculosis].

Objective To analyze the clinical features of patients with osteoarticular tuberculosis. Method This retrospective study included a cohort of 68 osteoarticular tuberculosis patients hospitalized in Peking Union Medical College Hospital from January 2013 to December 2020.Results The patients included 42(61.8%)males and 26(38.2%)females,with a median age of 56 years.Tuberculosis pathogen was detected in 39(57.4%)patients,and 29(42.6%)patients were diagnosed by clinical manifestations.The median time from onset to diagnosis was 4 months.The most common manifestations were pain and dysfunction(86.8%),followed by fever(47.1%),weight loss(36.8%),and night sweats(13.2%).Concomitant active tuberculosis in other organs was observed in 27(39.7%)patients.Unifocal and multifocal osteoarticular tuberculosis occurred in 51(75.0%)patients and 17(25.0%)patients,respectively,which mainly attacked thoracic and lumbar spines.Tuberculosis T cell test was positive in 92.7% patients.All the bone biopsies revealed epithelioid granuloma with/without necrosis,with 75.0% positive for mycobacterial DNA,55.1% positive for mycobacterial culture,and 20% positive for acid-fast staining.The risk of developing multifocal osteoarticular tuberculosis in the patients with weight loss was 5.333 times(P=0.013)that of the patients with stable weight.Conclusions The diagnosis of osteoarticular tuberculosis is difficult and tuberculosis T cell test is an effective means.Bone biopsy is the key to diagnosis,and the PCR of mycobacterial DNA shows the highest positive derection rate.Multifocal osteoarticular tuberculosis is not rare,especially in the patients with weight loss.Thus,a comprehensive imaging evaluation is recommended to avoid missed diagnosis.

Prevalence and risk factors of active tuberculosis in patients with rheumatic diseases: a multi-center, cross-sectional study in China.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 eligible patients were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet's disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p<0.001), taking azathioprine(AZA) within the past two years (OR=2.095, 95% CI: 0.986-4.450, p=0.054), exposing to glucocorticoids ≥30mg/d for more than four weeks within the past two years (OR=2.031, 95% CI: 1.247-3.309, p=0.004) and having evidences of previous TB (OR= 6.185, 95% CI: 3.487-10.969, p<0.001). The prevalence of ATB was higher in patients with rheumatic diseases compared to the general population. Patients with SLE or BD, prolonged exposure to moderate to high dose of glucocorticoids and previous TB were independent risk factors for ATB.

An Introduction to Next Generation Sequencing Bioinformatic Analysis in Gut Microbiome Studies.

The gut microbiome is a microbial ecosystem which expresses 100 times more genes than the human host and plays an essential role in human health and disease pathogenesis. Since most intestinal microbial species are difficult to culture, next generation sequencing technologies have been widely applied to study the gut microbiome, including 16S rRNA, 18S rRNA, internal transcribed spacer (ITS) sequencing, shotgun metagenomic sequencing, metatranscriptomic sequencing and viromic sequencing. Various software tools were developed to analyze different sequencing data. In this review, we summarize commonly used computational tools for gut microbiome data analysis, which extended our understanding of the gut microbiome in health and diseases.

Neurological manifestations of autoinflammatory diseases in Chinese adult patients.

OBJECTIVE: Systemic autoinflammatory diseases (SAIDs) are a group of disorders characterized by a dysregulation of innate immune system leading to multi-systemic inflammation. We aim to assess the neurological manifestations of Chinese adult patients with SAIDs. METHODS: Eighty adult patients (≥16 years) were diagnosed as SAIDs from April 2015 to June 2019, at the center of adult autoinflammatory diseases, Department of Rheumatology, Peking Union Medical College Hospital. Clinical and genetic features of these patients were collected. All patients underwent neurologic, ophthalmologic and otolaryngologic evaluation. RESULTS: Totally 31 out of 80 (38.8%) patients had neurological manifestations, including 14 familial Mediterranean fever (45.2%), 6 NLRP3-associated autoinflammatory disease (19.4%), 5 tumor necrosis factor receptor-associated periodic fever syndrome (16.1%), 5 NLRP12-associated autoinflammatory disease (16.1%), and 1 Yao syndrome (3.2%). Twenty patients (64.5%) were adult-onset. The median time of diagnosis delay was 11.7 years (0.5-50 years). The common neurological damage included headache (28 patients, 90.3%), sensorineural hearing loss (6, 19.4%), dizziness (4, 12.9%), cerebral infarction/hemorrhage (4, 12.9%), chronic aseptic meningitis (3, 9.7%), intracranial hypertension (3, 9.7%), papilledema (3, 9.7%), optic neuritis (2, 6.5%), and hydrocephalus (1, 3.2%). Severe neurological damage was observed in 8 patients (25.8%), including brain atrophy, hydrocephalus, complete hearing loss, chronic aseptic meningitis and optic neuritis. CONCLUSION: Neurological damage was diverse in SAIDs patients. Neurological symptoms should be fully realized by physicians, in not only pediatric but also adult patients with SAIDs. CSF analysis and brain images should be performed promptly. Early diagnosis and appropriate treatment are essential to avoid irreversible neurological complications.

Application of IFN-γ/IL-2 FluoroSpot assay for distinguishing active tuberculosis from non-active tuberculosis: A cohort study.

Currently available Interferon-γ release assay cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). This study aimed to evaluate the diagnostic accuracy of the IFN-γ/IL-2 FluoroSpot assay, which can simultaneously detect IFN-γ and IL-2 secretion, for differentiating ATB from non-ATB. 191 suspected ATB patients with positive T-SPOT.TB results were consecutively recruited. 64 (33.5%) participants had ATB, including 22 (34.4%) microbiologically or histologically confirmed TB and 42 (65.6%) clinically diagnosed TB. 119 (62.3%) cases were non-ATB and 8 (4.2%) were clinically indeterminate. After being stimulated with ESAT-6 and CFP-10 antigens, the median frequency and proportion of IFN-γ+IL-2- T cells were significantly higher in the ATB group than the non-ATB group (P < .001). The areas under the ROC curves of IFN-γ+IL-2- T cells were larger than those of total IFN-γ+ T cells (0.788 vs. 0.739, p = .323). With a cutoff value of 25 SFCs/250,000 PBMCs for frequency, sensitivity and specificity of this assay were 73.4% and 69.8% respectively. When combining the frequency and proportions of IFN-γ+IL-2- T cells, the sensitivity and specificity were increased to 95.3% in parallel testing and 83.2% in serial testing respectively. In conclusion, IFN-γ/IL-2 FluoroSpot assay is conducive for the diagnosis of ATB in patients with positive T-SPOT.TB results.

Clinical features of central nervous system infections and experience in differential diagnosis from neuropsychiatric lupus erythematosus in a cohort of 8491 patients with systemic lupus erythematosus.

BACKGROUND: In clinical practice, discrimination between central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE) and neuropsychiatric lupus erythematosus (NPSLE) could be urgent and critical yet extremely challenging. Given this, this study aimed to investigate the clinical features and outcomes of infections in the CNS in patients with SLE and to establish a simplified scoring system for guiding the discrimination of CNS infections from NPSLE. METHODS: A total of 95 patients who were identified as having CNS infections among 8491 SLE patients between January 1992 and January 2018 were included in this retrospective study. NPSLE patients admitted at the same period were randomly selected for comparison. Key factors either clinically valuable or statistically significant for discriminating CNS infections from NPSLE were integrated to build a simplified scoring system. Another group of 22 SLE patients complicated with suspected newly onset of CNS infections or NPSLE admitted after January 2018 was enrolled to verify the utility of the scoring system. RESULTS: Sixty-three positive pathogens were identified in 59 patients of the total 95 CNS infection cases. Compared with the NPSLE group, the CNS infections group had a longer disease duration (21.0 [3.0-50.0] vs. 1.0 [0-22.0] months, P < 0.05), exhibited more fever (96.8% vs. 23.2%, P < 0.001) and polymorphonuclear leukocyte leukocytosis in the cerebrospinal fluid (CSF) (45.6% vs. 0.5%, P < 0.05), and had significantly decreased CSF glucose (2.0 ± 1.3 vs. 3.3 ± 0.9 mmol/L, P < 0.01), whereas hypocomplementemia seemed to be a strong hint of NPSLE (44.6% vs. 77.4%, P < 0.001). A simplified scoring system integrated with 8 key factors was established for guiding clinical differential diagnosis. By setting the cutoff value at 4 and verifying in a group of SLE patients complicated with newly occurred suspected CNS infection or NPSLE, a sensitivity of 85.7% and specificity of 93.3% with the area under the curve (AUC) being 0.93 (95%CI 0.80-1.00) were obtained. CONCLUSIONS: CNS infections are a fatal complication of SLE and can be difficult to discriminate from NPSLE. A simplified scoring system may help to make preliminary discrimination of CNS infections from NPSLE.

Clinical features and outcomes of patients with fever of unknown origin: a retrospective study.

BACKGROUND: Few studies have reported the long-term clinical outcome of patients discharged with undiagnosed fever of unknown origin (FUO). In this study, the clinical features and outcomes of patients with unexplained fever were explored to improve our understanding of FUO. METHOD: Patients diagnosed with FUO at admission and discharged without final diagnoses after systematic examination in the department of infectious diseases at Peking Union Medical College Hospital between 2004 and 2010 were followed up by telephone. Medical records were reviewed, and the clinical features and outcomes of patients for whom follow-up data were available were summarized. RESULTS: Between 2004 and 2010, 58 patients with follow-up data, who were diagnosed with FUO at admission and did not have a final diagnosis at discharge, were enrolled in this study. The median duration of follow-up was 518 (0.4-830) weeks, and the fever duration was 24.6 (6.7-763.2) weeks. Final diagnoses were established in 11 cases (19%), and the diagnostic methods included clinical diagnosis, diagnostic therapy, genetic screening and biopsy pathology. The fever in 35 patients (60%) subsided during hospitalization or after discharge. Their condition was stable and self-limited after long-term follow-up, and they were ultimately thought to be cured. Two patients had periodic fever during prolonged observation: one patient needed intermittent use of nonsteroidal antiinflammatory drugs (NSAIDs), and the other needed intermittent use of NSAIDs and a steroid. Ten patients died during follow-up, with 9 deaths being caused by severe and worsening conditions related to the febrile illness. CONCLUSIONS: Long-term follow-up should be performed for patients with undiagnosed FUO. Some patients can obtain a definitive diagnosis by repeated multiple invasive examinations and diagnostic treatment. Most patients have a self-limited illness, and their prognosis is good.