Evidence for the gut-skin axis: Common genetic structures in inflammatory bowel disease and psoriasis.

BACKGROUND: Inflammatory bowel disease (IBD) and psoriasis (Ps) are common immune-mediated diseases that exhibit clinical comorbidity, possibly due to a common genetic structure. However, the exact mechanism remains unknown. METHODS: The study population consisted of IBD and Ps genome-wide association study (GWAS) data. Genetic correlations were first evaluated. Then, the overall evaluation employed LD score regression (LDSC), while the local assessment utilized heritability estimation from summary statistics (HESS). Causality assessment was conducted through two-sample Mendelian randomization (2SMR), and genetic overlap analysis utilized the conditional false discovery rate/conjunctional FDR (cond/conjFDR) method. Finally, LDSC applied to specifically expressed genes (LDSC-SEG) was performed at the tissue level. For IBD and Ps-specific expressed genes, genetic correlation, causality, shared genetics, and trait-specific associated tissues were methodically examined. RESULTS: At the genomic level, both overall and local genetic correlations were found between IBD and Ps. MR analysis indicated a positive causal relationship between Ps and IBD. The conjFDR analysis with a threshold of < 0.01 identified 43 loci shared between IBD and Ps. Subsequent investigations into disease-associated tissues indicated a close association of IBD and Ps with whole blood, lung, spleen, and EBV-transformed lymphocytes. CONCLUSION: The current research offers a novel perspective on the association between IBD and Ps. It contributes to an enhanced comprehension of the genetic structure and mechanisms of comorbidities in both diseases.

Alterations in the human oral microbiota in systemic lupus erythematosus.

BACKGROUND: Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. METHODS: We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. RESULTS: The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848-0.9483, p < 0.0001), 0.8422 (95% CI 0.7687-0.9157, p < 0.0001), and 0.8406 (95% CI 0.7677-0.9135, p < 0.0001) in the derivation, validation, and cross-regional validation groups, respectively. Moreover, as disease activity increased, Abiotrophia and Lactobacillales increased, while Phyllobacterium and unclassified Micrococcusaceae decreased. Finally, nine OTUs were selected to construct a classifier distinguishing posttreatment SLE patients from healthy controls, which achieved a diagnostic efficacy of 0.9942 (95% CI 0.9884-1, p < 0.0001). CONCLUSIONS: Our study comprehensively characterizes the oral microbiome of SLE and shows the potential of the oral microbiota as a non-invasive diagnostic biomarker in SLE.

Gut microbiota and acne: A Mendelian randomization study.

BACKGROUND: Prior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship underlying this association, we adopted the Mendelian randomization (MR) method, which offers a powerful approach to causal inference. METHODS: Summary statistics on gut microbiota and acne were obtained from the MiBioGen and FinnGen consortium, respectively. The causal relationship was assessed using multiple methods in a two-sample framework, including MR Egger, weighted median, inverse variance weighted (IVW), and weighted mode. Furthermore, the heterogeneity and horizontal pleiotropy analyses were conducted, along with the leave-one-out method. RESULTS: The IVW estimation indicated that Allisonella (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.18-1.70, p = 0.0002) and Bacteroides (OR = 2.25, 95% CI = 1.48-3.42, p = 0.0001) have adverse effects on acne. By contrast, Ruminococcus torques group (OR = 0.41, 95% CI = 0.25-0.65, p = 0.0002) showed a beneficial effect on acne. In addition, Candidatus soleaferrea (OR = 0.75, 95% CI = 0.60-0.95, p = 0.0149), Eubacterium coprostanoligenes group (OR = 0.67, 95% CI = 0.47-0.95, p = 0.0230), Fusicatenibacter (OR = 0.71, 95% CI = 0.52-0.97, p = 0.02897), and Lactobacillus (OR = 0.72, 95% CI = 0.58-0.90, p = 0.0046) showed suggestive associations with acne. CONCLUSION: The present investigation suggests a causal effect of gut microbiota on acne.

Clinical characteristics, outcome and prognostic factors in critically ill patients with lupus nephritis.

OBJECTIVES: To describe the clinical characteristics and outcome of patients with lupus nephritis (LN) in intensive care unit (ICU), identify prognostic factors and construct a predictive model of in-ICU survival. METHODS: A total of 505 ICU admissions of lupus patients were screened and LN patients confirmed by renal biopsy were enrolled. Clinical characteristics and outcome of patients in ICU were collected. A logistic regression analysis was performed to identify independent prognostic factors and a nomogram was plotted to construct a predictive model. RESULTS: A total of 70 patients with LN were enrolled. The median age of the patients was 28.5 years, and the median course of LN was two months. Renal pathology classes indicated that 38 patients were class IV, 11 were class IV+V, and 10 were class III. The most common primary cause of ICU admission was infection in 40 patients, followed by LN in 11 patients. Forty-one patients died in ICU. The multivariate analyses revealed that lactic acid (OR 1.682 [2.130-17.944], p=0.001), gamma-glutamyl transpeptidase (OR 1.057 [1.009-1.107], p=0.020), APACHE II (OR 3.852 [1.176-12.618], p=0.026), vasopressor (OR 10.571 [1.615-69.199], p=0.014) and platelet count (OR 0.967 [0.941-0.993], p=0.013) were independently associated with ICU survival of critical LN patients. A predictive model was constructed and validated. CONCLUSIONS: This study is the first to elucidate the features and identify prognostic factors in critically ill patients with LN. These findings could help clinicians to early identify high-risk patients of mortality, which consequently may reduce the mortality of critically ill patients with LN.

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal-Regulating Kinase 1 Pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

Mechanisms for the evolution of complex and diversely elaborated sepals in Iris identified by comparative analysis of developmental sequences.

PREMISE OF THE STUDY: Crested sepals, which have evolved at least five times in Iris, are adaxially elaborated with a sinuous and/or uneven median structure (crest) along the proximal-distal axis and sometimes with various lateral structures (ridges, crests, and linear protuberances) flanking the median crest. These structural elaborations are complex yet diverse in form, providing a good opportunity to investigate developmental mechanisms for the diversification of reproductive lateral organs. METHODS: Morphologies of the median and lateral structures at different developmental stages from selected crested sepals representing the major types of structural elaborations were recorded using scanning electron microscopy and light microscopy. Developmental (morphogenetic) events that contribute to changes in shape (e.g., sinuousness, unevenness) between consecutive stages were recorded. Developmental sequences-trajectories that consist of a series of developmental events-were compared in a phylogenetic context. KEY RESULTS: Three developmental events (development of outgrowths, greater expansion of the upper zone, and greater expansion of the lower zone), are shared across lineages, occur in the same developmental sequences, and are responsible for the changes in shape during the development of diverse structural elaborations. In addition, two novel developmental events and the development of trichomes on elaborate structures were observed within the core-crested clade. CONCLUSIONS: Developmental sequences are conserved across independently evolved crested lineages. Heterochronic and heterotopic shifts of developmental events play the major role in the diversification of elaborations of crested sepals in Iris. The evolution of novel developmental events and the development of trichomes also contribute to the diversity.

Analyzing serial cDNA libraries revealed reactive oxygen species and gibberellins signaling pathways in the salt response of Upland cotton (Gossypium hirsutum L.).

KEY MESSAGE: By comparing series full-length cDNA libraries stressed and control, the dynamic process of salt stress response in Upland cotton was studied, and reactive oxygen species and gibberellins signaling pathways were proposed. The Upland cotton is the most important fiber plant with highly salt tolerance. However, the molecular mechanism underlying salt tolerance in domesticated cotton was unclear. Here, seven full-length cDNA libraries were constructed for seedling roots of Upland cotton 'Zhong G 5' at 0, 3, 12 and 48 h after the treatment of control or 150 mM NaCl stress. About 3300 colonies in each library were selected robotically for 5'-end pyrosequencing, resulting in 20,358 expressed sequence tags (ESTs) totally. And 8516 uniESTs were then assembled, including 2914 contigs and 5602 singletons, and explored for Gene Ontology (GO) function. GO comparison between serial stress libraries and control reflected the growth regulation, stimulus response, signal transduction and biology regulation processes were conducted dynamically in response to salt stress. MYB, MYB-related, WRKY, bHLH, GRAS and ERF families of transcription factors were significantly enriched in the early response. 65 differentially expressed genes (DEGs), mainly associated with reactive oxygen species (ROS) scavenging, gibberellins (GAs) metabolism, signal transduction, transcription regulation, stress response and transmembrane transport, were identified and confirmed by quantitative real-time PCR. Overexpression of selected DEGs increased tolerance against salt stress in transgenic yeast. Results in this study supported that a ROS-GAs interacting signaling pathway of salt stress response was activated in Upland cotton. Our results provided valuable gene resources for further investigation of the molecular mechanism of salinity tolerance.

Trial and error: New insights into recombinant expression of membrane-bound insect cytochromes P450 in Escherichia coli systems.

Insect cytochromes P450 (CYP450s) are key enzymes responsible for a wide array of oxidative transformations of both endogenous and exogenous substrates. However, there is currently no a universal guideline established for heterologous expression of membrane-bound CYP450s, which hampers their downstream biochemical and structural studies. In this study, we conducted large-scale screening of protein overexpression in Escherichia coli using 71 insect CYP450 sequences and optimized the expression of a difficult-to-express CYP450 (CYP6HX3) using eight different optimizations, including selection of host strains and expression vectors, alternative of leader signal peptides, and N-terminal modifications. We confirmed that 1) Only insect CYP450s belonging to the CYP347 family could be expressed with N-terminal fusion of ompA2+ signal peptide in E. coli expression system. 2) E. coli Lemo 21 (DE3) effectively improved the expression of CYP6HX3 in the plasma membrane. 3) A brick-red appearance occurred frequently in the expressed thallus or membrane proteins, but this phenomenon could not necessarily indicate successful overexpression of target CYP450s. These findings provide new insights into the recombinant expression of insect CYP450s in E. coli systems and will facilitate the theoretical approaches for functional expression and production of eukaryotic CYP450s.

Case report: Adult NTRK-rearranged spindle cell neoplasms with TPM3-NTRK1 fusion in the pelvic.

NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are rare soft tissue tumor molecularly characterized by NTRK gene rearrangement, which occurs mostly in children and young adults, and rarely in adults. The abnormal tumor located in superficial or deep soft tissues of human extremities and trunk mostly, and rarely also involves abdominal organs. In this case, we report a malignant NTRK-RSCN that occurred in the pelvic region of an adult. The patient was found to have a large tumor in the pelvic region with a pathological diagnosis of infiltrative growth of short spindle-shaped tumor cells with marked heterogeneity. Immunohistochemistry of this patient showed positive vimentin, pan-TRK and Ki67 (approximately 60%) indicators with negative S100, Desmin and DOG1. Molecular diagnosis revealed c-KIT and PDGFRα wild type with TPM3-NTRK1 fusion, unfortunately this patient had a rapidly progressive disease and passed away. This case highlights the gene mutation in the molecular characteristics of NTRK-RSCNs, and the significance of accurate molecular typing for the diagnosis of difficult cases.

The Clinical Value of Comprehensive Nursing Intervention in Preventing Severe Lymphopenia and Improving the Survival Rate Among Patients with Sepsis.

Background: Intensive care unit (ICU) patients with sepsis who experience severe lymphopenia are at a higher risk of mortality, and they serve as a more accurate indicator of bacteremia compared to traditional infection markers. Aim: Our study aimed to examine the influence of severe lymphopenia on ICU mortality and outcomes in sepsis patients, while also evaluating the clinical significance of comprehensive nursing intervention in preventing severe lymphopenia. Methods: Patients with sepsis in the ICU at our hospital between January 2015 and January 2021 were split into a control group and a test group.The control group received regular nursing care, while the test group was provided with comprehensive nursing care in addition to the control group. The results encompassed mortality rates of 28 days, mortality rates of 1 year, and lengths of stay in the ICU. Results: Our attention was directed towards day 4 absolute lymphocyte counts, taking into account the receiver operating characteristic (ROC) outcome. Patients with severe lymphopenia were older, more patients with 2 above comorbidities, higher co-infection rates and SOFA score. In addition, patients with severe lymphopenia required longer days stay in ICU (P<0.001), and presented with higher 28-day mortality (P=0.038) and 1-year mortality (P=0.004). Patients in control group have a higher incidence of severe lymphopenia (P=0.006), 28-day mortality (P=0.015) and 1-year mortality (P=0.019) compared with the test group. Conclusion: Comprehensive nursing intervention can prevent the occurrence of severe lymphopenia, improve patients satisfaction and reduce mortality.

Genetically predicted levels of circulating cytokines and the risk of six immune skin diseases: a two-sample Mendelian randomization study.

Background: Circulating cytokines play a crucial role in the onset and progression of immune skin diseases. However, the causal relationships and the direction of causal effects require further investigation. Methods: Two-sample Mendelian randomization (MR) analyses were conducted to assess the causal relationships between 41 circulating cytokines and six immune skin diseases including alopecia areata, chloasma, hidradenitis suppurativa (HS), lichen planus (LP), seborrheic dermatitis, and urticaria, using summary statistics from genome-wide association studies. Reverse MR analyses was performed to test for the reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Results: Twelve unique cytokines showed a suggestive causal relationship with the risk of six immune skin diseases. Among them, the causal effects between 9 unique cytokines and immune skin diseases have strong statistical power. Additionally, the concentrations of six cytokines might be influenced by LP and urticaria. After Bonferroni correction, the following associations remained significant: the causal effect of beta-nerve growth factor on HS (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.226-2.177, p = 7.97e-04), interleukin (IL)-6 on LP (OR = 0.615, 95% CI = 0.481-0.786, p = 1.04e-04), IL-4 on LP (OR = 1.099. 95% CI = 1.020-1.184, p = 1.26e-02), and IL-2 on urticaria (OR = 0.712, 95% CI = 0.531-0.955, p = 2.33e-02). Conclusion: This study provides novel perspectives on the relationship between circulating cytokines and immune skin diseases, potentially providing valuable insights into their etiology, diagnostic approaches, and treatment.

Performance and mechanism of sacrificed iron anode coupled with constructed wetlands (E-Fe) for simultaneous nitrogen and phosphorus removal.

Three anodic biofilm electrode coupled CWs (BECWs) with graphite (E-C), aluminum (E-Al), and iron (E-Fe), respectively, and a control system (CK) were constructed to evaluate the removal performance of N and P in the secondary effluent of wastewater treatment plants (WWTPs) under different hydraulic retention time (HRT), electrified time (ET), and current density (CD). Microbial communities, and different P speciation, were analyzed to reveal the potential removal pathways and mechanism of N and P in BECWs. Results showed that the optimal average TN and TP removal rates of CK (34.10% and 55.66%), E-C (66.77% and 71.33%), E-Al (63.46% and 84.93%), and E-Fe (74.93% and 91.22%) were obtained under the optimum conditions (HRT 10 h, ET 4 h, CD 0.13 mA/cm2), which demonstrated that the biofilm electrode could significantly improve N and P removal. Microbial community analysis showed that E-Fe owned the highest abundance of chemotrophic Fe(II) (Dechloromonas) and hydrogen autotrophic denitrifying bacteria (Hydrogenophaga). N was mainly removed by hydrogen and iron autotrophic denitrification in E-Fe. Moreover, the highest TP removal rate of E-Fe was attributed to the iron ion formed on the anode, causing co-precipitation of Fe(II) or Fe(III) with PO43--P. The Fe released from the anode acted as carriers for electron transport and accelerated the efficiency of biological and chemical reactions to enhance the simultaneous removal of N and P. Thus, BECWs provide a new perspective for the treatment of the secondary effluent from WWTPs.

Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer's Disease through Network Pharmacology, Molecular Docking, and In Vivo Experiment.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease, severely reducing the cognitive level and life quality of patients. Byu dMar 25 (BM25) has been proved to have a therapeutic effect on AD. However, the pharmacological mechanism is still unclear. Therefore, this study aims to reveal the potential mechanism of BM25 affecting AD from the perspective of network pharmacology and experimental validation. METHODS: The potential active ingredients of BM25 were obtained from the TCMSP database and literature. Possible targets were predicted using SwissTargetPrediction tools. AD-related genes were identified by using GeneCards, OMIM, DisGeNET, and Drugbank databases. The candidate genes were obtained by extraction of the intersection network. Additionally, the "drug-target-disease" network was constructed by Cytoscape 3.7.2 for visualization. The PPI network was constructed by the STRING database, and the core network modules were filtered by Cytoscape 3.7.2. Enrichment analysis of GO and KEGG was carried out in the Metascape platform. Ledock software was used to dock the critical components with the core target. Furthermore, protein levels were evaluated by immunohistochemistry. RESULTS: In this study, 112 active components, 1112 disease candidate genes, 3084 GO functions, and 277 KEGG pathways were obtained. Molecular docking showed that the effective components of BM25 in treating AD were ß-asarone and hydroxysafflor yellow A. The most important targets were APP, PIK3R1, and PIK3CA. Enrichment analysis indicated that the Golgi genetic regulation, peroxidase activity regulation, phosphatidylinositol 3-kinase complex IA, 5-hydroxytryptamine receptor complexes, cancer pathways, and neuroactive ligand-receptor interactions played vital roles against AD. The rat experiment verified that BM25 affected PI3K-Akt pathway activation in AD. CONCLUSIONS: This study reveals the mechanism of BM25 in treating AD with network pharmacology, which provides a foundation for further study on the molecular mechanism of AD treatment.

Anal fistulotomy with one-stage shaped skin grafting for intersphincter anal fistulas: study protocol on a multicentre randomised controlled trial.

BACKGROUND: Anal fistulas are mainly treated via surgery. They can be difficult to treat without surgical intervention. Numerous procedures, such as fistulectomy and fistulotomy, are performed to treat anal fistulas and achieve good effects. However, the wounds created through fistulectomy and fistulotomy take a long time to heal. Therefore, a multicentre randomised controlled trial (RCT) is proposed to study the efficacy of one-stage shaped skin grafting at the surgical wound to heal low simple intersphincter anal fistulas. METHODS: This study is a multicentre, hospital-based RCT. It will be performed at three hospitals. A total of 104 patients with low simple intersphincter anal fistulas who meet the inclusion criteria will be included in this trial and will be allocated randomly to two groups (test and control groups). The patients in the test group will receive one-stage anal fistulotomy surgery combined with shaped skin grafting, and those in the control group will undergo anal fistulotomy only. All the operations will be performed by attending colorectal surgeons or surgeons of a higher level. Effectiveness and safety indicators will be observed, recorded and analysed. DISCUSSION: Anal fistulotomy can heal low simple intersphincter anal fistulas effectively and safely with a low recurrence rate. Skin grafts promote wound epithelisation significantly. We believe that skin grafting can treat low simple intersphincter fistulas with a short healing time. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000039174. Registered on 28 October 2020.

[Incidence of metabolic syndrome in systemic lupus erythematosus and its influence by glucocorticoids].

OBJECTIVE: To investigate the incidence and correlative factors of metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE). METHODS: A total of 116 SLE patients and 115 controls were enrolled into the study. The incidence of MS, SLE disease activity index (SLEDAI) of patients with SLE combined with MS (MS-SLE) and patients without MS (n-MS-SLE), lupus characteristics, cumulative glucocorticoids, administration dose of glucocorticoids and hydroxychloroquine were compared between SLE group and the control group. RESULTS: The incidence of MS of SLE group was obviously higher than that of the control (34.48% vs 14.78%, P < 0.05). The ratios of patients with lower HDL-C, higher TG and higher blood pressure in SLE group (50.86%, 56.03%, 46.55%) were higher than those in the controls (34.78%, 16.52%, 20.00%, all P < 0.05). MS-SLE group had significantly higher mean waist circumference, BMI, systolic blood pressure and diastolic blood pressure and lower HDL-C than n-MS-SLE group (all P < 0.05). No significant difference was found regarding duration of disease, renal involvement, ESR, C-reactive protein,high-sensitivity C-reactive protein, SLEDAI, cumulative and current glucocorticoids use in MS-SLE group and n-MS-SLE group. The ratio of patients taking hydroxychloroquine in n-MS-SLE group was higher than that of MS-SLE group (46.05% vs 15.00%, P < 0.05). CONCLUSIONS: Patients with SLE has a higher incidence rate of MS. Hydroxychloroquine may reduce their MS incidence.

Hematological malignancies in systemic lupus erythematosus: clinical characteristics, risk factors, and prognosis-a case-control study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic and complex multi-system autoimmune disorder. Higher risks of hematological malignancies (HM) were observed in SLE patients, which was associated with higher mortality. The mechanism and risk factors of HM oncogenesis in SLE patients are still under investigation. The aim of this study was to explore clinical characteristics, risk factors, and prognosis of SLE patients with or without HM in the Chinese population. METHODS: A retrospective, case-controlled study was conducted in 72 SLE patients between January 2013 and December 2020. Clinical and laboratory data were collected and compared between the two groups of patients with HM and those without HM. Logistic regression analysis was performed to determine risk factors of HM oncogenesis. The survival rate was estimated by Kaplan-Meier methods and Cox proportional hazards regression analysis. RESULTS: Among 72 SLE patients in this study, fifteen complicated with HM and 57 without HM were identified. The incidence rate of HM was approximately 0.24% with elevated standardized incidence ratios of lymphoma and leukemia (27.559 and 12.708, respectively). Patients with HM were older when diagnosed with SLE, with a higher frequency of infection and splenomegaly, lower levels of hemoglobin and high-density lipoprotein compared with those without HM. Fewer patients with HM expressed positive anti-dsDNA antibody (26.7% vs 66.7%, P = 0.005) or received hydroxychloroquine treatment (40.0% vs 86.0%, P = 0.001). Older age at SLE diagnosis (OR=1.122, 95% CI: 1.037-1.214) was regarded as an independent risk factor of HM oncogenesis. Female (RR= 0.219, 95% CI: 0.070-0.681) and hydroxychloroquine (RR= 0.281, 95% CI: 0.094-0.845) were protective factors of mortality in SLE patients. CONCLUSIONS: SLE patients with an older age are at an increased risk of HM carcinogenesis. The prognosis of male patients with SLE tends to be poorer whether complicated with HM. The association of antinuclear antibody spectrum, medication, and HM oncogenesis in SLE needs further investigation.

Boundary domain genes were recruited to suppress bract growth and promote branching in maize.

Grass inflorescence development is diverse and complex and involves sophisticated but poorly understood interactions of genes regulating branch determinacy and leaf growth. Here, we use a combination of transcript profiling and genetic and phylogenetic analyses to investigate tasselsheath1 (tsh1) and tsh4, two maize genes that simultaneously suppress inflorescence leaf growth and promote branching. We identify a regulatory network of inflorescence leaf suppression that involves the phase change gene tsh4 upstream of tsh1 and the ligule identity gene liguleless2 (lg2). We also find that a series of duplications in the tsh1 gene lineage facilitated its shift from boundary domain in nongrasses to suppressed inflorescence leaves of grasses. Collectively, these results suggest that the boundary domain genes tsh1 and lg2 were recruited to inflorescence leaves where they suppress growth and regulate a nonautonomous signaling center that promotes inflorescence branching, an important component of yield in cereal grasses.

Predictors of Mortality in Critically Ill Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) may require intensive care unit (ICU) admission due to different reasons, and the in-ICU mortality is high among AAV patients. The aim of this study was to explore the clinical features and risk factors of mortality of patients with AAV in the ICU. Methods: A retrospective study was conducted based on 83 AAV patients admitted to the ICU in a tertiary medical institution in China. Data on clinical characteristics, laboratory tests, treatment in ICU and outcomes were collected. The data were analyzed using univariate and multivariate logistic regression analysis to explore the variables that were independently related to mortality. Kaplan-Meier method was used to assess the long-term survival. Results: Among the 83 patients, 41 (49.4%) were female. The mean age of patients was 66 ± 13 years. Forty-four patients deceased, with the in-ICU mortality of 53%. The most common cause for ICU admission was active vasculitis (40/83, 48.2%). The main cause of death was infection (27/44, 61.4%) followed by active vasculitis (15/44, 34.1%). A multivariate analysis revealed that the Acute Physiology and Chronic Health Evaluation II (APACHE II) at ICU admission (OR = 1.333, 95% CI: 1.031-1.722) and respiratory failure (OR = 620.452, 95% CI: 11.495-33490.306) were independent risk factors of in-ICU death. However, hemoglobin (OR = 0.919, 95% CI: 0.849-0.995) was an independent protective factor. The nomogram established in this study was practical in predicting the risk of in-ICU mortality for AAV patients. Moreover, for 39 patients survived to the ICU stay, the cumulative survival rates at 0.5, 1, and 5 years were 58.3%, 54.2%, and 33.9%, respectively, and the median survival time was 14 months. Conclusion: In our study, active vasculitis was the most frequent reason for ICU admission, and the main cause of death was infection. APACHE II and respiratory failure were independent risk factors while hemoglobin was an independent protective factor of in-ICU mortality for AAV patients admitted to the ICU. The risk prediction model developed in this study may be a useful tool for clinicians in early recognition of high-risk patients and applying appropriate management.

Pharmacotherapy for Behçet's Disease and the Risk of Malignancy.

Background: Behçet's disease (BD) is associated with an increased risk of cancer. Few reports have been published on the relationship between drug exposure and the risk of cancer in patients with BD. Herein, we explored the relationship between pharmacologic interventions for BD and the risk of cancer. Methods: we carried out a retrospective nested case-control study in a cohort of BD patients from attending our institution. Among 1,148 patients, 22 cancer patients were individually 1:2 matched to 44 cancer-free controls. The following biochemical indicators were evaluated: routine blood analysis, liver and kidney function tests, inflammatory indexes, blood gas analysis, blood electrolyte and previous pharmacologic interventions to manage BD including systemic glucocorticoids, methotrexate, cyclosporine-A, azathioprine, cyclophosphamide (CYC), and thalidomide, which are considered the primary medicines used for the management of BD. Results: Among the 22 BD patients with cancers, myelodysplastic syndrome (MDS) (22.72%) was the most common type. Furthermore, CYC administration was significantly higher in BD patients with cancer compared with the cancer-free matched control group. Further, we observed that complement 4 (C4) (odds ratio [OR] = 0.0001, 95% confidence interval [CI]: 0.001-0.065) and hemoglobin (Hb) (OR = 0.891, 95% CI: 0.795-0.998) levels were independent protective factors for predicting cancer risk in BD patients on multivariate analyses. Conclusion: Our study revealed that CYC was associated with a high risk of cancer in BD patients. Furthermore, C4 and Hb are independent protective factors for oncogenesis in BD patients. These findings may provide references and suggestions for clinicians to select appropriate treatments and for the early recognition of high-risk patients to reduce cancer incidence in BD patients.

Development of a Novel Simple Model to Predict Mortality in Patients With Systemic Lupus Erythematosus Admitted to the Intensive Care Unit.

Background: Patients with systemic lupus erythematosus (SLE) may sometimes require admission to the intensive care unit (ICU), and the outcome is poor. The aim of this study was to explore the clinical features of patients with SLE in the ICU, identify prognostic factors, and develop and evaluate a prognostic model to predict in-ICU mortality of patients with SLE. Patients and Methods: This was a single center retrospective study in a tertiary medical institution in China. A total of 480 SLE patients with 505 ICU admissions from 2010 to 2019 were screened, and 391 patients were enrolled. The clinical feature and outcomes of the patients were analyzed. According to the random number table, patients were divided into two mutually exclusively groups named derivation (n = 293) and validation (n = 98). Prognostic factors were identified by a Cox model with Markov Chain Monte Carlo simulation and evaluated by latent analysis. The risk score was developed based on the derivation group and evaluated using the validation group. Results: Among the 391 patients, 348 (89.0%) patients were females. The median age of patients was 34 years, and the median course of SLE was 6 months. The median APACHE II and SLEDAI were 17 and 10, respectively. The average in-ICU mortality was 53.4% (95% CI, 48.5-58.4%). A total of 186 patients were admitted to the ICU due to infection. Pneumonia (320/391, 81.8%) was the most common clinical manifestation, followed by renal disease (246/391, 62.9%). Nine prognostic factors were identified. The model had C statistic of 0.912 (95% CI, 0.889-0.948) and 0.807 (95% CI 0.703-0.889), with predictive range of 5.2-98.3% and 6.3-94.7% for the derivation and validation groups, respectively. Based on distribution of the risk score, 25.3, 49.5, and 25.2% of patients were stratified into the high, average, and low-risk groups, with corresponding in-ICU mortality of 0.937, 0.593, and 0.118, respectively. Conclusion: Nine prognostic factors including age, white blood cell count, alanine transaminase, uric acid, intracranial infection, shock, intracranial hemorrhage, respiratory failure, and cyclosporin A/tacrolimus usage were identified. A prognostic model was developed and evaluated to predict in-ICU mortality of patients with SLE. These findings may help clinicians to prognostically stratify patients into different risk groups of in-ICU mortality, and provide patients with intensive and targeted management.