Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study.

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19. Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes. Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2-46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84-1.40 or 1.09, 0.92-1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01-1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26-1.64; 0.95, 0.36-2.54; and 1.01, 0.53-1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82-1.66; 1.18, 0.78-1.77; and 1.22, 0.92-1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31-2.81; 0.97, 0.25-3.74 and 1.05, 0.44-2.49, respectively) compared to those not using medication. Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

The probiotic Lactobacillus casei Zhang-mediated correction of gut dysbiosis ameliorates peritoneal fibrosis by suppressing macrophage-related inflammation via the butyrate/PPAR-γ/NF-κB pathway.

Peritoneal fibrosis is a complication of long-term peritoneal dialysis (PD) that restricts its clinical application for the treatment of end-stage renal disease. Lactobacillus casei Zhang (LCZ), a probiotic strain isolated from traditional fermented koumiss, exhibits health benefits such as anti-inflammatory and antioxidative effects, improvement of insulin resistance and mitigation of renal injury. However, whether LCZ can prevent peritoneal fibrosis remains unknown. Here, we assessed the effects of LCZ in a mouse model of PD-induced peritoneal fibrosis. Our results showed that the administration of LCZ significantly ameliorated peritoneal fibrosis in experimental mice. Macrophage infiltration, inflammatory M1 polarization and inflammatory cytokines in peritoneal dialysis effluents were effectively reduced by LCZ. Meanwhile, LCZ corrected gut dysbiosis and enriched beneficial bacteria that produce short-chain fatty acids, specifically Dubosiella, Lachnospiraceae, Parvibacter, and Butyricicoccus. Correspondingly, the local butyrate level in peritoneal dialysis effluents was significantly elevated by LCZ. Mechanistically, we found activation of PPARγ and inhibition of the NF-κB pathway in LCZ-treated mice, an observation that was replicated in a butyrate-treated macrophage cell line. In conclusion, our study suggests that LCZ is beneficial for preventing PD-induced peritoneal fibrosis through modulating the gut microbiota, enhancing butyrate production, activating PPARγ, and suppressing NF-κB-mediated inflammation.

Effects of probiotics on non-alcoholic fatty liver disease: a review of human clinical trials.

Non-alcoholic fatty liver disease (NAFLD) is a global public health issue, of which the prevalence is about 25% worldwide. The incidence of NAFLD is increasing in patients with obesity, type 2 diabetes (T2DM) and the metabolic syndrome. The crosstalk between gut microbiota and metabolism-related diseases has been raised great concern. Patients with NAPLD were observed with disruption of gut microbiota. Several researches showed that gut microbiota was the determination in the progression of NAFLD by the experiments using fecal microbiota transplants. The application of probiotics, as one of the most important strategies for the regulation of gut microbiota disorder, have been explored whether it is beneficial to gut-related diseases of intestine-distal organs. Some probiotics were showed to improve the liver parameters and phenotype in patients with NAFLD. The oral intake of them might become the effective management for the prevention and treatment of NAFLD. In this review, we summarized the human clinical trials focusing on the effects of probiotics on NAFLD to give some evidential reference for the administration of NAFLD.

[Distribution Characteristics and Health Effects of Bioaerosols in Spring over Xi'an City].

A large amount of fluffy caktins appears in spring in Xi'an that may cause air pollution and lead to health risks such as asthma. In this study, bioaerosol, PM2.5, and fluffy catkins were collected from different sample points (traffic site and campus site) in Xi'an in spring. The variations in bioaerosol, fluffy catkins, and the bacterial community structure were investigated using culture-dependent and high-throughput sequencing methods. The results showed that the concentration of culturable bacteria was significantly higher (P=0.027) at the traffic site. The concentration of culturable bacteria at the traffic site was 2.7 times that of fungi, whereas the concentration of culturable fungi at the campus site was 1.4 times higher than that of bacteria. The peak concentrations of culturable bacteria and fungi appeared at 08:00 a.m. The size distribution of culturable bacteria showed a bimodal pattern, whereas that of culturable fungi showed a unimodal distribution. Soil and vegetation were the main sources of atmospheric microorganisms (85.9%), and Proteobacteria was the most abundant phylum in both fluffy catkins and PM2.5, accounting for 91.3% (traffic site) and 99.1% (campus site) of the fluffy catkins. Actinobacteria, Firmicutes, Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus were the dominant phyla in PM2.5. Some genera were opportunistic pathogen bacteria in the fluffy catkins, such as Enterobacter and Pseudomonas, which can lead to infection and diarrhea risks. These results could provide fundamental data on potential health risks of spring-borne bioaerosols.

Clinical value of plasmablasts in predicting disease relapse in patients with IgG4-related disease.

OBJECTIVES: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD). METHODS: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated. RESULTS: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/µL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012). CONCLUSIONS: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points • The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. • The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. • The application of LEF is an independent protective factor for disease relapse in IgG4-RD.

Size distribution, community composition, and influencing factors of bioaerosols on haze and non-haze days in a megacity in Northwest China.

Bioaerosols have become a major environmental concern in recent years. In this study, the diurnal variations and size distributions of bioaerosols, as well as airborne bacterial community compositions and their influencing factors on haze and non-haze days in Xi'an, China, were compared. The results indicated that the mean bacteria and fungi concentrations on non-haze days were 1.7 and 1.4 times of those on haze days, respectively, whereas the mean total airborne microbe (TAM) concentration was higher on haze days. Bacteria concentrations were the lowest in the afternoon, and the TAM concentration exhibited a bimodal distribution with two peaks coinciding with traffic rush hours. On haze days airborne fungi was mainly attached to PM2.5, whereas bacteria and TAM were mainly distributed in coarse PM. The relative abundance of Chao1, Shannon and Simpson indices of bacterial communities were higher in the non-haze day samples, for the reason that high PM2.5 levels with a large specific surface area may absorb more toxic and harmful substances on haze days, which should affect microbial growth. At the generic level, the relative abundance of Rhodococcus, Paracoccus, Acinetobacter, and Kocuria on haze days was higher than that on non-haze days, indicating a higher risk of contracting pathogenic pneumonia. The results of the redundancy analysis revealed that PM2.5 and water-soluble inorganic ions (WSIIs, NO3-, SO42+, and NH4+) strongly affected the bacterial communities on non-haze days, especially Acinetobacter. The atmospheric oxidation capacity (Ox) had a significant effect on bacterial communities during haze episodes, which were positively correlated with Paracoccus, Deinococcus, Sphingomonas, and Rubellimicrobium and were negatively correlated with Rhodococcus. These results provide valuable data to elucidate the formation and evolution of bioaerosol between haze and non-haze events and its potential threats to human health.

[Measurement Analysis and Superposed Effect of Residential Indoor Air Pollutants in Xi'an].

To understand the levels of indoor air pollution and protect public health, our research group conducted monitoring of the concentrations of indoor pollutants (formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), n-butyl acetate, ethylbenzene, styrene, and undecane) and a health effect assessment for 830 households of Xi'an City from December 2017 to December 2020. Simultaneously, the superposed effect of pollutants was analyzed. The results showed that the exceedance rates of formaldehyde, benzene, toluene, TVOC, and xylene were 92.1%, 39.7%, 11.7%, 8.9%, and 1.2% respectively, among which formaldehyde was the most serious pollutant. There was no significant difference in pollutant concentration and exceedance among different room types. The concentration of pollutants was the highest in summer due to the influence of temperature, humidity, and other factors. The results of the human health risk assessment showed that there were carcinogenic risks of formaldehyde and benzene for different age groups (children, adolescents, adults, and the elderly); children and the elderly were more at risk, whereas xylene, ethylbenzene, and toluene were at low risk (HI<1). The superposed effect of pollutants showed that superposition between indoor pollutants did exist, resulting in the obvious increase in pollutant toxicity. This study provides data reference and scientific basis for the characteristics and healthy effects of indoor residential pollutants in Xi'an City.

Pu'er tea rich in strictinin and catechins prevents biofilm formation of two cariogenic bacteria, Streptococcus mutans and Streptococcus sobrinus.

Cariogenic bacteria, such as Streptococcus mutans and Streptococcus sobrinus, are main pathogens responsible for human dental caries. Pu'er tea is empirically observed to prevent tooth decay. Besides caffeine and catechins commonly found in oolong tea, strictinin is also found as an abundant phenolic compound in Pu'er tea. Infusion of Pu'er tea as well as single compound, strictinin, caffeine or (-)-epigallocatechin gallate (EGCG) was examined for its inhibitory effects on S. mutans and S. sobrinus. Relatively weak inhibition of bacterial growth was observed for these Pu'er tea constituents. However, biofilm formation of S. mutans or S. sobrinus was strongly prevented by the infusion of Pu'er tea as well as by strictinin or EGCG, but not caffeine. Relatively, strictinin showed a higher potency than EGCG to prevent biofilm formation. Anti-caries effect of Pu'er tea seems to be resulted from the prevention of biofilm formation of cariogenic bacteria mainly by strictinin and catechins.

Eosinophilic fasciitis associated with generalized morphea and IgA nephropathy.

Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by increased peripheral blood eosinophils and diffuse fasciitis, generalized morphea (GM) is a subtype of localized scleroderma, and IgA nephropathy is a chronic glomerulonephritis caused by abnormal deposition of IgA in the mesangial area of the glomeruli. We describe a 49-year-old male patient with hard skin, cutaneous hyperpigmentation, and proteinuria. The patient had suffered from a long disease course of hard skin, while urine protein was newly detected. Finally, the clinical presentation and physical examination, limb MRI, skin biopsy, and renal biopsy confirmed the diagnosis of eosinophilic fasciitis associated with generalized morphea and IgA nephropathy. This case is the first report of EF associated with GM and IgA nephropathy.

Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). METHODS: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. RESULTS: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). CONCLUSION: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.

Cd contamination status and cost-benefits analysis in agriculture soils of Yangtze River basin.

Soil is a fundamental carrier to support for human living and development and has been polluted seriously by heavy metals. This fact highlights the urgency to realize soil heavy metal pollution prevention through soil heavy metals contamination status assessment and root cause analysis. The previous research tends to focus status assessment and source identification without consideration of economic aspect. This study realized the systematic analysis from status assessment, sources identification and economic-environmental cost-benefits analysis in the Yangtze River basin. Through the spatial difference comparison among the provinces of upper, middle and lower in the Yangtze River basin, it revealed that anthropogenic influence is the main reason caused the current Cd contamination in Yangtze River basin. An interesting finding is that the human caused Cd concentration contribution amount is nearly the same between upstream and downstream which is all about 0.1 mg/kg, while they have quite different economic scale. It indicated that due to the difference of the scale and structure of local economy, and the level of cleaner production and pollution treatment, some regions could own high economic-benefits and low environmental cost, which it is opposite in other regions. The geographic location and natural resources is the root cause to form the environmental cost-economic benefits difference among regions. The convenient traffic promoted downstream to develop large amount and high quality of economy. The natural mineral resources promoted midstream to develop resources based economy. The poor condition of traffic and natural resources has restricted the development of Qinghai province, and made it has the highest Cd pollution intensity. The results would provide effective economic management measures for better soil quality and sustainable development goals achievement.

When brucellosis met the Assessment of SpondyloArthritis international Society classification criteria for spondyloarthritis: a comparative study.

OBJECTIVES: To distinguish brucellosis patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) from SpA patients. METHODS: Brucellosis patients diagnosed from September 2012 to December 2017 who met the ASAS classification criteria for SpA were analyzed with clinical characteristics and laboratory and imaging examinations. Axial or peripheral SpA patients were respectively included into the comparative analysis with a 4:1 ratio. RESULTS: Twenty-two brucellosis (10 axial and 12 peripheral) patients (male, 16 cases; 72.72%; mean (S.D.) age, 40.23 (16.49) years) and 88 SpA patients were included. All brucellosis patients had been misdiagnosed or considered as SpA before admission to our center. The brucellosis patients had shorter disease duration (axial, P = 0.001; peripheral, P = 0.108). More than half (59.09%) of the patients had contact history with livestock. The low back pain (LBP) of brucellosis patients was generally less improved with exercise (axial, P = 0.001; peripheral, P = 0.008). More brucellosis patients had myalgia (axial, P < 0.001; peripheral, P = 0.071) or fever (axial, P < 0.001; peripheral, P = 0.107). None of them had positive HLA-B27. Blood culture tests were performed in all brucellosis patients and only 4 (18.18%) were positive. Twenty (90.91%) brucellosis patients were gold-immunochromatographic assay (GICA) positive. Bone marrow edema and bone erosion in sacroiliac joints were respectively detected in 100% (10/10) and 90% (9/10) axial brucellosis patients by MRI. Adjacent muscle involvement was found in 80% (8/10) of the patients. CONCLUSIONS: Indicators including disease duration, contact history of livestock, features of LBP, myalgia, fever, and HLA-B27 can help the differential diagnosis of brucellosis and SpA. GICA test and sacroiliac joints MRI can furtherly confirm the diagnosis of brucellosis.

Disability and health-related quality of life in Chinese patients with rheumatoid arthritis: A cross-sectional study.

AIM: The objective of this study was to evaluate the impact of rheumatoid arthritis (RA) on physical function and health-related quality of life (HRQoL) in China. METHOD: A cross-section survey was conducted in 21 general hospitals in China. Eight hundred and seven patients were recruited. Data on demographics, clinical data, physical function (Stanford Health Assessment Questionnaire Disability Index, HAQ-DI) and HRQoL (Study Short Form 36 Health Survey, SF-36) were collected on site. RESULTS: In our cohort, physical function was impaired in 77.6% of patients (HAQ-DI >0). The median (interquartile range, IQR) of HAQ-DI was 0.750 (0.125, 1.500). Rated by HAQ-DI 0-1, >1-2, and >2-3, percentage of patients with mild, moderate and severe disability was 61.0%, 25.4%, and 13.6%, respectively. Older age, long disease duration, presence of extra-articular manifestations, tender joint count (TJC), overall status (assessed by patient Global Visual Analogue Scale [G-VAS] and physician G-VAS) and lacking disease-modifying anti-rheumatic drugs were identified as predictive factors for worse physical function (P < .05). The composite scores of SF-36 in the observed patients were: physical component summary 40.4 (IQR 27.4, 60.3), and mental component summary 49.0 (IQR 33.6, 70.9). Impaired physical health may be predicted by low income, presence of extra-articular manifestations, TJC, patient G-VAS and high HAQ-DI. Predictors for suboptimal mental health were low income, physical labor, married status, increased swollen joint count (SJC), physician G-VAS and high HAQ-DI. CONCLUSION: Rheumatoid arthritis has profound effects on physical function and HRQoL in Chinese patients. Patients with identified predictive factors for poor outcome should be closely monitored.

The value of 18F-FDG PET/CT in the distinction between retroperitoneal fibrosis and its malignant mimics.

OBJECTIVE: To discuss the utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) in the diagnosis of idiopathic retroperitoneal fibrosis (iRPF). METHODS: IRPF patients diagnosed between September 2011 and June 2016 were included. Retroperitoneal malignancy patients were included as control. The morphological features and FDG uptake of retroperitoneal lesions were measured along with lymph node (LN) mapping. RESULTS: Seventy-one iRPF patients were included. Fifteen lymphoma patients and 6 retroperitoneal metastatic malignancy patients were included as control. Significant differences in morphological features were observed between iRPF and lymphoma but not retroperitoneal metastatic carcinoma. Compared with malignancy, iRPF displayed a lower frequency of high-FDG-uptake retroperitoneal lesions (P = 0.017) and a lower mean maximum standardized uptake value (SUVmax) (P < 0.001). LNs located at axillary, retroperitoneal, supraclavicular, inguinal or peritoneal sites were more frequently observed in retroperitoneal malignancy, therefore, were defined as specific LNs. The area under the curve (AUC) for SUVmax was 0.893 with a sensitivity of 85.7% and a specificity of 80.3%, when the cut-off value of the SUVmax was 6.23. The AUC for the logistic regression model combining the lesions above renal arteries, the SUVmax and the number of specific LNs was 0.987 with a sensitivity of 90.5% and a specificity of 98.6%. The risk stratification model analysis indicated that most of the retroperitoneal malignancy patients were at moderate or high level, while most of the iRPF patients were at low risk. CONCLUSIONS: Retroperitoneal malignancy can mimic iRPF morphologically. 18F-FDG PET/CT can help to distinguish iRPF from retroperitoneal lymphoma and metastatic malignancy.

A carbonothioate-based highly selective fluorescent probe with a large Stokes shift for detection of Hg2.

Mercury (Hg) is one of the heavy metal pollutants in the environment. Even a very small amount of mercury can cause serious harm to human beings. Herein, we reported a new carbonothioate-based fluorescent probe for the detection of Hg2+ without interference from other metal ions. This probe possessed a very large Stokes shift (192 nm), which could improve the detection sensitivity by minimizing the interferences resulted from self-absorption or auto-fluorescence. With the addition of Hg2+ to the probe solution, considerable fluorescence enhancement was observed. Additionally, the Hg2+ concentration of 0-16 µM and fluorescence intensity showed a good linear relationship (y = 22106× + 53108, R2  = 0.9955). Finally, the proposed probe was used to detect Hg2+ in real water samples, and its result was satisfactory. Therefore, our proposed probe would provide a promising method for the determination of Hg2+ in the environment.

Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease.

The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.

Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review.

BACKGROUND: Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD. AIM: To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD. METHODS: We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI). RESULTS: A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed. CONCLUSION: The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD.

3d-4f Metal-Organic Framework with Dual Luminescent Centers That Efficiently Discriminates the Isomer and Homologues of Small Organic Molecules.

A 3d-4f luminescent metal-organic framework (MOF), [Tb2(Cu8I8)(C12H8NO2)6(H2O)4]·5C4H8O2 (4), and three analogues {[La2(Cu8I8)(C12H8NO2)6(C4H8O2)2(H2O)2]·3C4H8O2·2H2O (1), [Ce2(Cu8I8)(C12H8NO2)6(H2O)4]·5C4H8O2 (2), and [Eu2(Cu8I8)(C12H8NO2)6(H2O)4]·5C4H8O2 (3)}, were self-assembled from copper(I) halide clusters and lanthanide metal ions with an organic linker [3-(pyridin-4-yl)benzoic acid] under solvothermal conditions. Compound 4 with high quantum yield (Φ = 68%) exhibits reversible luminescence behavior, accompanying the removal and recovery of guest molecules (1,4-dioxane). Because of the unique porous structure and dual luminescent centers of compound 4, it can efficiently differentiate benzene series with different sizes and provide readouts in corresponding optical signals. Furthermore, it also can unambiguously discriminate the isomers, homologues, and other small molecules with similar structural motifs from one another. The luminescent color of the MOF sensor in different guest solvents has obvious changes that can be clearly distinguished by the naked eye. This multicolor luminescence originates from emissions of the dual luminescent centers, and the emissions have shifted, enhanced, weakened, or quenched to different degrees.

[Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance].

OBJECTIVE: To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. METHODS: Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. RESULTS: Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05). CONCLUSION: Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.