Lactate dehydrogenase predicts disease progression outcome in COVID-19 patients treated with Azvudine.

Background: Azvudine has been approved in China for the treatment of COVID-19 patients. Previous studies have suggested a correlation between high levels of lactate dehydrogenase (LDH) and the severity of COVID-19. However, the impact of LDH levels in COVID-19 patients receiving Azvudine treatment remains unclear. Methods: In this retrospective cohort study, we analyzed the data of 351 hospitalized COVID-19 patients who were consecutively treated with Azvudine, with or without high LDH levels. The clinical features, treatment strategies and prognosis data were collected and analyzed. Results: Among the 351 hospitalized patients with COVID-19 treated with Azvudine (119 with high-LDH levels), the median age was 69 years (range 58-78), and 213 (60.7%) were male. Common symptoms included cough (86.0%), expectoration (73.5%), fever (69.8%), polypnea (47.6%) and poor appetite (46.4%). Patients with high LDH levels exhibited significantly elevated leucocyte and neutrophil counts, elevated level of myocardial enzymes, as well as higher levels of inflammatory markers such as interleukin-6, interleukin-10, procalcitonin, C reactive protein, ferritin, and prolonged erythrocyte sedimentation rate upon admission. COVID-19 patients with high-LDH levels had higher rates of corticosteroid therapy, non-invasive and invasive mechanical ventilation, worsened and death (2.5% vs. 0%). The Cox proportional hazard model demonstrated that high LDH levels (adjusted hazard ratio = 5.27; 95% confidence interval: 1.19, 14.50) were associated with a more unfavorable composite disease progression outcome among COVID-19 patients treated with Azvudine, after accounting for potential confounding variables. Conclusion: High-LDH levels predict a worse composite disease progression outcome in COVID-19 patients treated with Azvudine.

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. METHODS: With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. RESULTS: By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798). CONCLUSION: We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients.

MTX in genetically distinctive Chinese psoriatic patients remains less explored. The present study aimed to determine the impact of HLA-Cw*06 on MTX response in a Chinese psoriasis patient population. A total of 204 patients with psoriasis were enrolled in this study. Clinical data and DNA samples from all patients were collected. The allele of HLA-Cw*06 genotyping was detected using direct Sanger sequencing. This study enrolled 204 patients with psoriasis, including 47 (23.04%) psoriatic arthritis patients, 157 (76.96%) patients free of psoriatic arthritis. Overall, 110 (53.92%) of all patients carried the HLA-Cw*06 allele. This frequency in patients with arthritis-free psoriasis was higher than that in those with psoriatic arthritis (58.59 vs. 38.30%, P = 0.014). After 8 weeks of MTX treatment, the arthritis-free psoriasis patients, who tested positive for the HLA-Cw*06 allele, showed significant improvement compared to those who tested negative (For PASI50, 78.57 vs. 55.22%, P = 0.02, and for PASI75, 51.11 vs. 34.33%, P = 0.036). The psoriatic arthritis-free patients who carried the HLA-Cw*06 allele in combination with the ABCB1 rs1045642 CC genotype showed the highest improvement. A regression model containing HLA-Cw*06, rs1045642T > C, and initial PASI scores was used to construct the efficacy prediction model of MTX, which yielded AUC values of 73.2 and 75.6% for PASI50 and PASI75 to MTX, respectively, in arthritis-free psoriasis patients. The HLA-Cw*06 allele is associated with optimal response to MTX treatment in arthritis-free Chinese psoriasis patients. When combined with clinical indicators, the polymorphism explained more than 75% of the individual efficacy differences.

Clinical difference between single subtype and mixed subtype chronic urticaria: A retrospective study.

BACKGROUND: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. AIMS: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. METHODS: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. RESULTS: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. LIMITATIONS: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. CONCLUSION: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients.

Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis.

BACKGROUND: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative. OBJECTIVES: To investigate the effect of PM2.5 on IgE-mediated mast cell responses through an IgE-mediated mouse model and mast cell activation. METHODS: The ß-hexosaminidase release and a BALB/c model of passive cutaneous anaphylaxis (PCA) was used to test IgE-mediated mast cells activation in vitro and in vivo. RNA-Seq technique was conducted to study the gene expression profile. Reactive oxygen species (ROS) production was measured by flow-cytometry. RT-PCR,WB and ELISA were performed to examine targeting molecules expression. RESULTS: PM2.5 facilitated IgE-mediated degranulation and increased cytokines expression in mast cells. Meanwhile, the Evan's blue extravasation as well as serum cytokines in mice was increased after treatment with PM2.5. Furthermore, PM2.5 treatment dramatically increased the expression of Gadd45b which is an oxidative stress molecule that directly activates down-stream pathway, such as MEKK4/JNK. PM2.5 treatment activated MEKK4, JNK1/2 but not ERK1/2 and p38. Meanwhile, Knockdown of Gadd45b significantly attenuated PM2.5-mediated JNK1/2 activation and expression of cytokines. In addition, a JNK1/2-specific inhibitor SP600125 blocked IgE-mediated mast cell activation and cytokine release in PCA model mice. Moreover, PM2.5 treatment increased the ROS level and ROS inhibitor dramatically blocked the PM2.5-induced ROS production and reversed the PM2.5-mediated gene expression in the mitochondrial respiratory chain. CONCLUSIONS: PM2.5 regulates ROS production through Gadd45b/MEKK4/JNK pathway, facilitating IgE-mediated mast cell activation.

Therapeutic effect of Bacillus Calmette-Guerin polysaccharide nucleic acid on mast cell at the transcriptional level.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Dysfunction of immune cells, such as T cells, mast cells, and basophils, is involved. Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN), an immunomodulator partially extracted from BCG, can be used in the combined treatment of CSU with an unknown mechanism. METHODS: To study the therapeutic effect and mechanism of BCG-PSN on CSU, we initially assessed the clinical efficacy in 110 enrolled CSU patients of 4-week antihistamine monotherapy vs. antihistamine plus BCG-PSN combined therapy. Subsequently, to explore the further mechanism of BCG-PSN, the mast cell line RBL-2H3 pretreated with BCG-PSN was used to evaluate the transcriptional expression profiles via lncRNA sequencing. Real time PCR was conducted to validate the candidate gene expression. RESULTS: We found no significant difference in treatment efficacy between the BCG-PSN group (71.7%) and the monotherapy group (71.9%). However, the average time of complete relief in the BCG-PSN group was significantly shorter than that in the monotherapy group (36.77 ± 17.33 vs. 51.27 ± 16.80, p = 0.026). In vitro experiments showed that BCG-PSN inhibited ß-hexosaminidase release rates in IgE-sensitized RBL-2H3 cells (p < 0.001). Sequencing data revealed the expression profiles of functional genes, including a significant decrease in Erb-B2 receptor tyrosine kinase 4, which can be regulated by the nuclear factor kappa B (NF-κB) pathway. DISCUSSION: CSU is a chronic, recurrent disease with complex pathogenesis. Mast cells and basophils are the primary target cells of the disease. BCG-PSN decrease the ß-HEX release rates and regulated IgE-mediated mast cell activation in RBL-2H3 cells by mediating immune-related gene expression including ERBB4. These findings suggest that BCG-PSN may mediate ERBB4 expression via the NF-κB pathway and may have value in the treatment of CSU.

[Clinical characteristics and prognosis for 126 patients with severe drug eruption].

OBJECTIVE: To explore the clinical characteristics of various types of severe drug eruption and common sensitized drugs, and to provide clinical references for reducing the incidence of severe drug eruption.
 Methods: The clinical data regarding 126 cases of severe drug eruption were analyzed retrospectively from June 2009 to May 2017 in Xiangya Hospital, Central South University.
 Results: In the 126 cases of severe drug eruption, the distribution of men and women ratio was 1:1.38. The length of stay was (12.7±9.8) d. The most common type was Steven-Johnson syndrome; the most dangerous type was drug-induced bullosa epidermolysis. The most common sensitized drug category in these patients was antibiotics; the most common single sensitizing drug was carbamazepine, following by allopurinol.
 Conclusion: Severe drug eruption occurs mostly in young and middle-aged people. Steven-Johnson syndrome is the most common type; drug hypersensitive syndrome has the longest length of hospital course. Mortality rate of drug-induced bullosa epidermolysis is the highest. Timely stop using of allergens, early using glucocorticoids, and timely combination of non-glucocorticoids treatment (such as intravenous immunogloblin, plasma exchange and hemodialysis), can improve the efficacy and reduce the complications and mortality. 
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[Clinical characteristics of urticaria in children versus adults].

OBJECTIVE: To study the clinical characteristics of urticaria in children versus adults, and to provide reference for the etiological analysis, disease evaluation, and treatment of urticaria in children. METHODS: The clinical data of 2 411 patients with urticaria who visited the Department of Dermatology at Xiangya Hospital of Central South University from January 2013 to May 2017 were collected to study their socio-demographic characteristics. The clinical characteristics of urticaria were compared between the 68 children and 672 adults of the 740 patients with complete follow-up data. RESULTS: Among the 411 pediatric patients, 314 (76.4%) had acute urticaria; among the 2 000 adult patients, 896 (44.8%) had chronic spontaneous urticaria. The causes of acute urticaria in children included infection (41%, 16/39). The accompanying symptoms of acute urticaria in children mainly included abdominal pain and diarrhea (44%, 17/39), while those in adults mainly included chest distress and shortness of breath (32%, 11/34). Compared with the adult patients, the pediatric patients had significantly lower chronic urticaria activity scores before and after treatment (P<0.05), a significantly higher rate of response to second-generation antihistamines (82.1% vs 62.2%; P<0.05), and a significantly higher proportion of individuals with a personal and family history of urticaria (P<0.05). CONCLUSIONS: Acute urticaria is more commonly seen than chronic urticaria in children with urticaria, and the main accompanying symptoms are abdominal pain and diarrhea, which are different from adults with urticaria. Chronic urticaria has a better treatment outcome in children than in adults. The most frequently seen cause of acute urticaria is infection in children. Atopic children may be susceptible to urticaria.