Search

Objective To investigate the neonatal and maternal outcomes of patients treated with belimumab during pregnancy. Materials and methods We retrospectively collected patients who were treated with belimumab during pregnancy from January 2018 to October 2020 in a tertiary referral hospital in Taiwan. All patients had clinical and serological features of systemic lupus erythematosus or antiphospholipid syndrome and had been treated accordingly. The patients’ medical and obstetric history, obstetric complications and fetal outcomes were collected by chart review. Results A total of 13 pregnancies in 13 patients were included. The median age was 38 years (interquartile range 32–41 years), 46.2% had a history of recurrent pregnancy loss, and the median number of treatment courses with belimumab (400 mg per dose) was two. There were 11 live births (84.6%, 11 of 13). One episode of omphalitis was noted in one fetus, who recovered well with antibiotic treatment. No fetus had leukopenia, lymphopenia, neutropenia, or thrombocytopenia in the days after birth. No fetal anomalies were found in this series. Among the six patients with a past history of recurrent pregnancy loss, four had live births. Conclusion This study provides new evidence for the use of belimumab in pregnant patients. No increase in the risk of fetal anomalies or severe infection was noted in the patients who were exposed to belimumab during pregnancy. Cautious monitoring is necessary if belimumab is used in pregnant patients, and more data are still needed to validate its safety.

Takeda G protein-coupled receptor 5 (TGR5) is a promising target for treating metabolic syndrome and inflammatory diseases. Herein, we identified a new series of betulinic acid derivatives as potent TGR5 agonists, which show remarkable activity on human (h) and canine (c) TGR5 but exhibit unpromising activity on murine (m) TGR5. Species difference was also observed with many other reported TGR5 agonists. Therefore, we screened 29 amino acids which were conserved in hTGR5 and cTGR5 but different in mTGR5 and found a key amino acid, H88 in mTGR5 (Y89 in hTGR5), which contributed to the species difference. With the CRISPR/Cas9 system, the mTGR5H88Y mutation was introduced into mice, and the optimized compound 11d-Na displayed a significant glucose-lowering effect and stimulated GLP-1 and insulin secretion in TGR5H88Y mice but not in wild-type animals. Taken together, our study provides a useful tool to bridge the gap of species difference and discovers a potent TGR5 agonist for further investigation.

Progressive multifocal leukoencephalopathy (PML) is one of the rare but lethal infectious complication in patients with SLE, manifesting progressive central nervous demyelination caused by JC virus (JCV). There have been no effective antiviral agents so far; however, immune checkpoint inhibitors (ICI) have been demonstrated as potential treatments by reinvigorating antiviral T-cell activity against JC virus. To date, sixteen PML cases treated with anti-PD-1 have been reported; however, there was no report addressing the use of ICI in patients with concomitant PML and rheumatic disease, possibly due to the concern for possible autoimmune disease flare-up. In addition, treatment outcomes of these ICI-treated cases were heterogeneous. Experiences from these cases suggested that high disease burden, JC viral load in CSF, and severe immunosuppression status at baseline may predict poor response to treatment. Our case, a 62-year-old woman with long-standing SLE, turned out to have a delayed but effective response to prolonged ICI treatment despite of her high JC viral load and immunosuppressed status caused by high-dose steroid and rituximab. To our knowledge, this is the first case report with SLE complicated with PML clinically improved by pembrolizumab treatment without consequent immune related adverse events (irAE). Considering the lethal nature of PML and absence of effective medication, ICI is a reasonable consideration in patients with SLE and progressive PML.

Extrauterine growth restriction (EUGR), a serious risk that potentially impairs the growth of preterm infants after birth and during childhood, triggers a thought of how to achieve optimal catch-up growth during hospitalization.We aimed to access the incidence of optimal catch-up growth in small-for-gestational-age (SGA), appropriate-for-gestational age (AGA) and large-for-gestational-age (LGA) infants, and identify the factors for optimal catch-up growth in preterm infants during hospitalization. Premature infants admitted to Shanghai Children’s Medical Center within 24 hours after birth from January 1,2016 to December 31, 2018 were enrolled. Prenatal, neonatal etiological, and nutrition data were collected and analyzed to identify factors associated with optimal catch-up growth during hospitalization. 105 (9.9%) of 1065 preterm newborns achieved predischarge optimal catch-up growth, including 27 (17.2%) of 157 SGA, 74 (8.5%) of 868 AGA, and 4 (10.0%) of 40 LGA infants. Logistic regression analysis indicated SGA, avoiding BPD and less days to regain birth weight as the contributing factors of optimal catch-up growth during hospitalization.Conclusion: SGA infants showed greater potential in predischarge optimal catch-up growth. Early abundant nutrition and avoiding BPD are essential for achieving optimal catch-up growth during hospitalization.

Background Rituximab is known to be associated with a high resolved hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation in rheumatic patients receiving rituximab is limited. Aims To assess the HBV reactivation in HBsAg-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcomes and factors associated with HBV reactivation were analyzed. Results After a median follow-up period of 3.3 years, 21 patients developed HBV reactivation, among which 17 patients were positive for anti-HBc and 4 were negative. Thirteen patients had clinical hepatitis flare, while 8 patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, and undetectable serum anti-HBs level at rituximab initiation were associated with HBV reactivation. There was no significant difference in the HBV reactivation risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBV reactivation (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas, patients with negative anti-HBc, especially those without vaccination at birth, were still at risk for HBV reactivation after receiving rituximab. Regular monitoring of HBV serology should be considered for all HBsAg-negative patients receiving rituximab for autoimmune diseases.

Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy review and meta-analysis to determine the performance of anti-DFS70 antibodies in patients with a positive anti-nuclear antibody (ANA) test result to exclude SARD. We searched PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 22 February 2021, and included studies examining the diagnostic accuracy of anti-DFS70 antibodies in patients with a positive ANA test result. The results were pooled using a hierarchical bivariate model and plotted in summary receiver operating characteristic curves. R software and Stata Statistical Software were used for the statistical analysis. Eight studies with 4168 patients were included. The summary sensitivity was 0.19 (95% confidence interval: 0.12–0.28) and the specificity was 0.93 (95% confidence interval: 0.88–0.96). The area under the curve was 0.69 (95% confidence interval: 0.64–0.72). The meta-regression analysis showed that targeting only ANA-associated rheumatic disease was associated with higher specificity. In addition, the studies with a non-SARD prevalence of

Objective: Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.Methods: This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.Results: This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).Conclusions: Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.

IntroductionDespite advances in diabetic retinopathy (DR) medications, early identification is vitally important for DR administration and remains a major challenge. This study aims to develop a novel system of multidimensional network biomarkers (MDNBs) based on a widely targeted metabolomics approach to detect DR among patients with type 2 diabetes mellitus (T2DM) efficiently.Research design and methodsIn this propensity score matching-based case-control study, we used ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system for serum metabolites assessment of 69 pairs of patients with T2DM with DR (cases) and without DR (controls). Comprehensive analysis, including principal component analysis, orthogonal partial least squares discriminant analysis, generalized linear regression models and a 1000-times permutation test on metabolomics characteristics were conducted to detect candidate MDNBs depending on the discovery set. Receiver operating characteristic analysis was applied for the validation of capability and feasibility of MDNBs based on a separate validation set.ResultsWe detected 613 features (318 in positive and 295 in negative ESI modes) in which 63 metabolites were highly relevant to the presence of DR. A panel of MDNBs containing linoleic acid, nicotinuric acid, ornithine and phenylacetylglutamine was determined based on the discovery set. Depending on the separate validation set, the area under the curve (95% CI), sensitivity and specificity of this MDNBs system were 0.92 (0.84 to 1.0), 96% and 78%, respectively.ConclusionsThis study demonstrates that metabolomics-based MDNBs are associated with the presence of DR and capable of distinguishing DR from T2DM efficiently. Our data also provide new insights into the mechanisms of DR and the potential value for new treatment targets development. Additional studies are needed to confirm our findings.

Background and objectives Accumulating evidences suggest that chronic systemic inflammation (CSI) is independently associated with large number of major non-communicable chronic diseases (NCDs) ranging from metabolic disorders to cancers, and neutrophil-to-lymphocyte ratio (NLR) has been accepted as a novel, convenient marker for CSI response. Testosterone deficiency in men is linked to high risk of NCDs. This cross-sectional study aimed to investigate the individual and joint association of bioavailable testosterone (BIOT) and aging with NLR. Methods A total of 132 male adults were enrolled during Jan. 2011 and Oct. 2017 in the first affiliated hospital of University of Science and Technology of China. Local weighted regression (LOESS) and multivariable generalized linear regression models were utilized to comprehensively examine the individual and joint association between BIOT and age with NLR. Results Obvious linear relationships between NLR and BIOT or age were observed with the LOESS models. NLR was negatively correlated to BIOT after adjusting for some potential confounding factors (P = 0.034). As compared to the lowest quartile of BIOT, the adjusted decrease of NLR for the 2nd, 3rd and 4th quartiles were 0.40, 0.64 and 0.72, respectively. Meanwhile, NLR was observed to be independently correlated to elevated age (P = 0.043). Furthermore, as compared to the counterparts, men over 70 years combined with plasma BIOT less than 4.7 nmol/L had the highest NLR level, which suggested that low BIOT and aging jointly correlated to the level of NLR (P = 0.005). Conclusion BIOT deficiency and aging were individually and jointly correlated to CSI. Men over 70 years combined with BIOT

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.

Oxidative DNA damage pathogenically links to some major diseases. This study aimed to comprehensively assess the association between serum total cholesterol (TC) and oxidative DNA damage based on propensity score matching (PSM) method. A total of 407 participants chronically exposed to arsenic via drinking water from China were enrolled. Oxidative DNA damage was determined with urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Serum TC was classified into favourable TC (FTC, TC5.18 mmol/L) and unfavourable TC (NFTC, TC ≥5.18 mmol/L) categories. Multivariable generalised linear regression model was applied to examine the association. Of 407 participants, 125 pairs with FTC and NFTC subjects were matched using PSM. Urinary 8-OHdG/creatinine levels in NFTC were significantly higher than those in FTC category (

OBJECTIVE: To perform a narrative review of the prognostic value of prognostic nutritional index (PNI) in cancers. BACKGROUND: Prognostic estimation greatly determines the treatment approach in various cancers. The PNI, calculated using the serum albumin level and total lymphocyte count, is a useful indicator to assess nutritional and immunological conditions. The PNI represents a low-cost, easy-to-perform, noninvasive, rapid, and standardized tool for estimating the prognosis of cancer. Many studies have aimed to clarify the prognostic value of PNI for various types of cancer. METHODS: We summarize the studies, particularly the systematic reviews and meta-analyses, that have examined the prognostic value of PNI in common cancers. CONCLUSIONS: The relevant studies indicate that low PNI is an independent prognostic factor for decreasing overall survival in many types of cancers. Disease-free survival and progression-free survival were also associated with PNI in some types of cancer including lung cancer and renal cell carcinoma. Therefore, we suggest that the measurement of PNI is a useful method to identify cancer patients that have a worse prognosis and that the treatment strategy for these patients be adjusted accordingly. We hypothesize that maintaining good nutritional status during treatment may improve outcomes of various cancers.

Sugammadex, an antagonist of neuromuscular blocking drugs, was used to rapidly reverse rocuronium induced neuromuscular blockade by encapsulating free rocuronium molecules as inclusion complexes. Because it can enhance the rapid recovery after surgery, summadex is gradually used in clinical. There are relatively few reports about anaphylactic reaction to it. We will present a case of severe anaphylactic shock induced by summadex, as the first in China. Author biography: At present, Wei pan is a junior doctor in Shuguang Hospital Affiliated to Shanghai University of traditional Chinese medicine. She graduated from the anesthesia College of Xuzhou Medical University with a master's degree at the age of 27.

Until now, there are no approved treatment against COVID-19. Hydroxychloroquine (HCQ) was hypothesized to be active against SARS-CoV2 via antiviral and anti-inflammatory effect; however, HCQ for COVID-19 in clinical use remained debating. In this preliminary report, we presented six patients with mild to moderate COVID-19. They were treated with HCQ for 14 days from the day of COVID-19 diagnosis. Serial viral load from respiratory specimens were performed every other day. Cytokine profile was checked before HCQ initiation and on the 14th day of HCQ treatment. All patients receiving HCQ completed 14-day course without complication. Among the six patients, the mean duration from symptom onset to last detectable viral load was 34 ± 12 days, which was similar to those without specific treatment in previous reports. Low level of interferon-gamma was noted in all patients of different stage of infection and three patients had elevation of IL-17 level. Prolonged virus shedding is still observed regardless HCQ. The impact of HCQ on cytokine kinetics remained unclear; however, IL-17 could be an inflammatory marker for disease status monitor and a potential therapeutic target.

Diabetic retinopathy (DR), the most common microvascular complication of diabetes and leading cause of visual impairment in adults worldwide, is suggested to be linked to abnormal lipid metabolism. The present study aims to comprehensively investigate the relationship between n-6 polyunsaturated fatty acids (PUFAs) and DR. This was a propensity score matching based case–control study, including 69 pairs of DR patients and type 2 diabetic patients without DR with mean age of 56.7 ± 9.2 years. Five n-6 PUFAs were determined by UPLC-ESI-MS/MS system. Principle component regression (PCR) and multiple conditional logistic regression models were used to investigate the association of DR risk with n-6 PUFAs depending on independent training and testing sets, respectively. According to locally weighted regression model, we observed obvious negative correlation between levels of five n-6 PUFAs (linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid and arachidonicacid) and DR. Based on multiple PCR model, we also observed significant negative association between the five n-6 PUFAs and DR with adjusted OR (95% CI) as 0.62 (0.43,0.87). When being evaluated depending on the testing set, the association was still existed, and PCR model had excellent classification performance, in which area under the curve (AUC) was 0.88 (95% CI: 0.78, 0.99). In addition, the model also had valid calibration with a non-significant Hosmer–Lemeshow Chi-square of 9.44 (P = 0.307) in the testing set. n-6 PUFAs were inversely associated with the presence of DR, and the principle component could be potential indicator in distinguishing DR from other T2D patients.

We read with great interest the article by Petri et al demonstrating that higher hydroxychloroquine (HCQ) blood levels were associated with lower risk of thrombotic event in patients with systemic lupus erythematosus (SLE). (1) A mean blood level of 1068 ng/mL and a most recent level of 1192 ng/mL and above had a protective effect. The dose response implied a therapeutic threshold of HCQ. However, a previous study indicated a range of HCQ blood level from 1177 to 3513 ng/mL predicted later development of HCQ retinopathy. (2) Obviously, there's a great overlap between the protective level from thrombosis and toxic level of retinopathy. The optimal therapeutic range is so narrow (1068 to 1177 ng/mL) that dose titration to target this level would be difficult in clinical practice. It seems that the dilemma of avoiding retinopathy while maintaining the benefit of HCQ still exists.

Background and Objectives. Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage renal disease across the world. Early identification of DKD is vitally important for the effective prevention and control of it. However, the available indicators are doubtful in the early diagnosis of DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. Materials and Method. This case-control study involved 44 T2DM patients. Among them, 24 participants with DKD were defined as the cases and another 20 without DKD were defined as the controls. The ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry system was applied for the assessment of the serum metabolic profiles. Comprehensive analysis of metabolomics characteristics was conducted to detect the candidate metabolic biomarkers and assess their capability and feasibility. Result. A total of 11 differential metabolites, including Hexadecanoic Acid (C16:0), Linolelaidic Acid (C18:2N6T), Linoleic Acid (C18:2N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6-Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 20:4, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis. Conclusion. Serum metabolites might act as sensitive and specific biomarkers for DKD early detection. Further longitudinal studies are needed to confirm our findings.

To investigate the diurnal fluctuations of macular vessel density (VD) in primary open-angle glaucoma (POAG) and healthy subjects using optical coherence tomography angiography. A total of 22 POAG eyes and 15 healthy eyes were included in this study. Macular VD, intraocular pressure, and blood pressure were repeatedly measured from 8 AM to 8 PM at a 2-h interval on a single day. Main outcome measures: the macular VD measurements, their diurnal fluctuations, including the difference between their maximal and minimal value (max–min) and their coefficient of variation (CV) in superficial capillary plexus (SCP) and deep capillary plexus (DCP). The mixed-effects model was performed to compare the fluctuations between groups. After adjusted age, the diurnal fluctuations of macular VD in SCP and DCP were significantly higher in POAG eyes compared with healthy subjects (max–min: 6.65 ± 3.54%, 3.92 ± 3.63%, respectively; p = 0.037 and CV: 0.06 ± 0.03, 0.04 ± 0.03, respectively; p = 0.003). The fovea VD in DCP of POAG eyes was higher than in healthy subjects (31.52 ± 4.68% and 25.71 ± 3.70%, p = 0.009). However, there was no significant difference between the fovea VD in SCP in two groups (20.97 ± 4.75% and 19.29 ± 4.35%, p = 0.670). The diurnal macular superficial VD measured in most of the participants was lower in the morning. Whether it is a max–min or a CV assessment method, the POAG eyes had more significant diurnal fluctuations of macular VD than healthy controls, suggesting impaired vascular autoregulation in POAG eyes.

ObjectivesWe investigated the association of specific serum amino acids (AAs) with the odds of arsenic-induced skin lesions (AISL) and their ability to distinguish patients with AISL from people chronically exposed to arsenic.DesignCase–control study.SettingThree arsenic-exposed villages in Wuyuan County, Hetao Plain, Inner Mongolia, China were evaluated.ParticipantsAmong the 450 residents aged 18–79 years, who were chronically exposed to arsenic via drinking water, 56 were diagnosed as having AISL (defined as cases). Another 56 participants without AISL, matched by gender and age (±1 year) from the same population, were examined as controls.Main outcome measures and methodsAA levels were determined by ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry-based metabolomics analysis. Potential confounding variables were identified via a standardised questionnaire and clinical examination. Multivariable conditional logistic regression model and receiver operating characteristic curve analyses were performed to investigate the relationship between specific AAs and AISL.ResultsTryptophan and phenylalanine levels were negatively associated with AISL (pConclusionsSpecific AAs may be linked to AISL and play important roles in early AISL identification.Trial Registration numberNCT02235948.

Alternative splicing of messenger RNAs (mRNAs) is a common and conserved biological process in eukaryotes. The aberrancy or disruption of different alternative splicing forms may cause alterations of cell functions and result in diseases. It is proposed that alternative splicing may play a critical role in the mechanisms of carcinogenesis. By studying a large dataset in The Cancer Genome Atlas database, a recent study showed that alternative splicing, particularly exon-exclusion, is a powerful prognosis factor in serious subtype of ovarian cancer. However, the characteristics of alternative splicing has not been studied in other subtypes. In this study, we focus on the alternative splicing events, i.e. single exon-inclusion or -exclusion, in clear-cell ovarian cancer subtype. The subtype appears to have particularly high incidence in Asians comparing to Europeans and Americans and tend to be drug resistant. Transcriptomes were obtained from tumors and their paired-normal tissues from five patients. PSI-values, which represent the proportions of alternative splicing events of an exon, were calculated in both tumor and paired-normal tissues. Differences of PSI-values between tumors and paired-normal were examined by a significant test based on Conditional Beta Regression model. In total, we identified ~200 exons covering 52 genes with significant differences between cancer and paired-normal tissue (p < 0.001) including gene ERP29 and PAM which were previously identified in serous subtypes.

PURPOSE To investigate the prevalence and associations of myopic anisometropia in Chinese adults. METHODS A total of 3,791 Chinese refractive surgery candidates with myopia (25.15±7.09 years old, Mean±SD) were recruited. All eyes underwent a standardized ophthalmological examination. Associations between myopic anisometropia and age, gender, spherical ametropia, astigmatism, and axial length (AL) were analyzed by means of the chi-squared test, nonparametric Kruskal-Wallis or Mann-Whitney test, binomial logistic regression analyses, and multivariate logistic regression analysis. RESULTS The mean myopic anisometropic level was 0.96 D and prevalence of myopic anisometropia was 29.62% (defined as myopic anisometropia ≥1.00 D). The prevalence and severity of myopic anisometropia increased with age, larger interocular AL difference, and higher cylindrical power (all P

Background:Interstitial lung disease (ILD) is one of the main contributor to morbidity and mortality in patients with primary Sjogren syndrome (pSS), and whether immunosuppressive treatments are effective for pSS-ILD is uncertain. Cyclophosphamide (CYC) and rituximab (RTX) are effective in stabilizing pulmonary function in patients with ILD caused by systemic sclerosis, inflammatory myositis, and rheumatoid arthritis1,2. Reports regarding the treatment response for cyclophosphamide or rituximab in pSS-ILD patients are lacking.Objectives:To investigate whether add-on CYC or RTX in addition to steroid and oral DMARDs leads to greater improvement in pulmonary function test than conventional treatment in patients with pSS-ILD with impaired baseline pulmonary function.Methods:pSS-ILD patients with ILD confirmed by a chest computed tomography were screened. Those with imparied baseline pulmonary function test (FVCResults:This study enrolled 22 patients. The median age of these patients was 65. Among them, 68% were female and 18% were smokers. The median baseline FVC was 63.5% and the median DLCO was 54.4%. The predominant CT pattern was NSIP (54%), followed by UIP (22%), LIP (13.6%) and OP (9%) (table 1).Five patients received steroid and oral DMARDs alone (hydroxychloroquine +/- azathioprine), while 17 patients received add-on CYC and/or RTX (8 patients received CYC, 3 received RTX, and 6 received CYC and RTX). There was no significant difference in baseline characteristic between these two groups (table 1).With a median follow-up period of 9.8 months (interquartile range 7.6 - 13.4 months) after treatment, the FVC improved significantly from 61.3% to 65.5% (p=0.013) in CYC/RTX group, while the FVC improvement was not significant in steroid/oDMARD group (figure 1A). In CYC/RTX group, patients with non-UIP pattern (NSIP, LIP and OP) on chest CT had significant FVC improvement (p=0.021), contrasting to the patients with UIP pattern on chest CT (figure 1B).Conclusion:In pSS patients with ILD and impairment of pulmonary function at baseline (FVCReferences:[1]Wells AU, Denton CP. Interstitial lung disease in connective tissue disease--mechanisms and management. Nat Rev Rheumatol. 2014 Dec;10(12):728-39.[2]Gao Y, Moua T. Treatment of the Connective Tissue Disease-Related Interstitial Lung Diseases: A Narrative Review. Mayo Clin Proc. 2020 Mar;95(3):554-573.Table 1.Baseline characteristics of patients with Sjögren’s syndrome and interstitial lung diseaseTotal(n = 22)Steroid/oDMARDs (n = 5)Add-on CYC/RTX(n = 17)Comparison between two groups (p-value)Age, year, median (IQR)65.1 (61.7 - 69.1)64 (64.6 - 67.4)65.6 (61.6 - 69.2)0.88Female sex, n (%)15 (68%)4 (80%)12 (70%)1.00Smoking, n (%)4 (22%)0 (0%)4 (21%)0.54Baseline FVC, % of predicted value, median (IQR)63.6% (53.8 - 68.2)63.9% (63.7 - 67.5)61.3% (50.2 - 68.2)0.43Baseline DLCO, % of predicted value, median (IQR)54.4% (39.4 - 66.4)69.1% (57.8 - 75.5)52.1% (38.5 - 58.1)0.12CT pattern, n (%)NSIP - 12 (54%)NSIP 1 (20%)NSIP - 11 (65%)-UIP - 5 (22%)UIP 1 (20%)UIP - 4 (24%)LIP - 3 (13.6%)LIP 2 (40%)LIP -1 (6%)OP - 2 (9%)OP 1 (20%)OP -1 (6)UIP pattern, n (%)5 (22%)1 (20%)4 (24%)1.00CYC, cyclophosphamide; oDMARDs, oral DMARDs; RTX, rituximabFigure 1.FVC change before and after the immunosuppressive treatmentDisclosure of Interests:None declared

Background:Systemic lupus erythematosus (SLE) could affect multiple parts of the eye. (1,2) Also, there is risk of ocular toxicity associated with treatment, such as hydroxychloroquine.(3) Early diagnosis is essential to avoid major ocular complications. However, complaints of eye discomfort may be vague, and various presentations may pose challenges on rheumatologists. Knowing the real-world prevalence of ocular problems in patients with SLE is important and helpful, yet this has been less common to be reported.Objectives:To describe the prevalence of various ophthalmologic diagnoses in patients with SLE.Methods:This is a retrospective observational study conducted in a tertiary hospital in Taipei, Taiwan. Patients diagnosed with SLE in the period between 1st Jan, 2002 and 31th Dec, 2015 and evaluated by ophthalmologists in 2 years before 29th Jan, 2021 were included. Demographic and clinical data, and ophthalmologic diagnoses were recorded by chart review.Results:A total of 121 patients were included, and 118 (97.5%) were female. Average age was 46.2 years [standard deviation (SD) 11.4 years] upon ophthalmologic evaluation, and average duration suffering from lupus was 11.6 years (SD 3.3 years). Keratoconjunctivitis sicca (n = 48, 39.7%), myopia (n = 39, 32.2%), and cataract (n = 21, 17.4%) were the most common findings. It was also noted that suspicious finding of hydroxychloroquine retinal toxicity was found in 12 patients (9.9% of total patients). Also, two patients had lupus retinopathy, and another two were diagnosed with cytomegalovirus retinitis. In addition, glaucoma was diagnosed in 9 patients (7.4%), which seemed to be higher than the general population.Conclusion:Higher prevalence of different ocular problems is noted in this cohort of SLE patients. Keratoconjunctivitis sicca was the most common ocular diagnosis, which is consistent with literature. However, high rates of myopia, cataract, glaucoma, and suspicious hydroxychloroquine retinal toxicity were also found. Above result warrants more aggressive ophthalmologic evaluation in SLE patients. More research on the association of lupus and different ocular diseases is needed in the future.References:[1]Silpa-archa S, Lee JJ, Foster CS. Ocular manifestations in systemic lupus erythematosus. Br J Ophthalmol. 2016 Jan;100(1):135–41.[2]Sivaraj RR, Durrani OM, Denniston AK, Murray PI, Gordon C. Ocular manifestations of systemic lupus erythematosus. Rheumatology (Oxford). 2007 Dec;46(12):1757–62.[3]Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018;14(12):693–703.Table 1.Demographic data and ophthalmologic diagnosis of patients with systemic lupus erythematosus (N = 121)Variablen (% of N)Age (years) average (SD)46.2 (11.4)Disease duration average (SD)11.6 (3.3)Female sex118 (97.5)Chronic medical disease Hypertension28 (23.1) Diabetes mellitus4 (3.3) Dyslipidemia7 (5.8) Cancer3 (2.5) End-stage renal disease1 (0.8)Ophthalmologic diagnosis Keratoconjunctivitis sicca48 (39.7) Myopia39 (32.2) Cataract21 (17.4) Glaucoma9 (7.4) Suspicious retinopathy related to HCQ12 (9.9) Unspecified retinopathy5 (4.1) Lupus retinopathy2 (1.7) CMV retinitis2 (1.7) Central retinal vein thrombosis1 (0.8) Retinal break1 (0.8) Optic neuritis1 (0.8) Vitreal hemorrhage1 (0.8) Myodesopia4 (3.3) Scleritis1 (0.8)SD, standard deviation; HCQ, hydroxychloroquine; CMV, cytomegalovirus.Disclosure of Interests:None declared

Tuberculosis pleural effusion (TPE) is common in clinical practice, and its diagnosis remains a challenge for clinicians. Ziehl-Neelsen staining, PE Mycobacterium tuberculosis culture, and biopsy are the gold standards for TPE diagnosis; however, they are time-consuming, invasive, observer-dependent, and insensitive. PE markers represent a rapid, low-cost, and non-invasive objective diagnostic tool for TPE. In the past decades, several PE biomarkers have been developed, and their diagnostic accuracy has been evaluated in many studies. Here, we reviewed the literature to summarize the diagnostic accuracy of these biomarkers, especially using the evidence from systematic review and meta-analysis. The current research strongly suggests that adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) have extremely higher diagnostic accuracy for TPE, while the diagnostic accuracy of interferon gamma release assays (IGRAs), tumor necrosis factor-α (TNF-α), and interferon-γ-induced protein 10 kDa (IP-10) is moderate. Although some evidence supports C-X-C motif chemokine ligand 9 (CXCL9), CXCL11, CXCL12, sFas ligand, angiotensin-converting enzyme (ACE), calpain-1, spectrin breakdown products (SBDP), matrix metalloproteinase-1 (MMP-1), soluble CD26 (sCD26), soluble interleukin 2 receptor (sIL-2R) as useful diagnostic markers for TPE, more support is needed to validate their diagnostic accuracy. Finally, nucleic acid amplification tests (NAATs) have extremely high diagnostic specificity, but their sensitivity is low. Taken together, ADA is the preferred marker for TPE because its low cost and suitability for standardization.

Background. Calreticulin has been identified to play a critical role in innate and adaptive immune responses. However, little is known about the role of calreticulin in sepsis with a characteristic of immune disorder. This study was aimed at investigating whether plasma calreticulin level increases in sepsis and its association with sepsis severity. Methods. This retrospective analysis evaluated sepsis patients who were admitted to the intensive care unit (ICU). Healthy subjects were also included as controls. Plasma samples were collected from the patients within 48 h after ICU admission as well as the healthy subjects. Plasma calreticulin levels were measured via the enzyme-linked immunosorbent assay. Results. In total, 127 sepsis patients and 40 healthy controls were included. Calreticulin was significantly increased in sepsis patients than in healthy controls. Furthermore, the level of plasma calreticulin was significantly higher in nonsurvivors than in survivors. Patients with calreticulin levels>343.5 pg/ml showed lower cumulative survival than those with levels<343.5 pg/ml. Conclusion. Calreticulin level was positively correlated with the severity of sepsis. High calreticulin level indicated poor prognosis of sepsis patients.

ObjectiveTo investigate the validity and feasibility of a self-administered home vision examination programme in China.DesignCross-sectional study.SettingYueqing, China.ParticipantsA two-stage convenience sampling procedure was used to randomly select 600 households from 30 communities participating in the Yueqing Eye Study (YES). The aim of YES is to encourage home-based vision screening, reporting of visual acuity (VA) annually through social media and encouraging people to attend follow-up clinic appointments as a way to improve eye care access for adults with VA ≤+0.5 log of the minimum angle of resolution (logMAR).InterventionsHousehold screeners (one per household) who tested other family members’ VA completed a questionnaire on family structure, demographic information and knowledge about screening procedures. Other family members then underwent confirmatory VA testing by researchers.Outcome measuresThe completion rate of home-based VA screening, its sensitivity and specificity were used to evaluate validity. Factors that determined whether families participated in the self-VA screening were used to evaluate feasibility.Results345 (66%) of the 523 (87.2%) households with valid data form their home-based vision examinations also were retested by researchers. There was no statistically significant difference in scores on the family-administerd or researcher-administerd VA test (VA≤+0.5 logMAR, p=0.607; VA >+0.5 logMAR, p=0.612). The sensitivity and specificity of home-based vision screening were 80.5% (95% CI 70.2% to 86.9%) and 95.1% (95% CI 92.6% to 96.8%), respectively. 14.7% (77/523) of tested respondents had VA ≤+0.5 logMAR. Predictors of performing home screening for VA remaining in regression models included higher economic status (‘fair and above’ vs ‘poor’: OR 1.74; 95% CI 1.08 to 2.76; p=0.022), age (ConclusionSelf-administered home vision screening is reliable and highly accepted by Chinese adults.

Background The accuracy of total calcium and its corrected value for predicting critically high and critically low ionized calcium in critical illness is controversial. The aim of this study was to investigate whether the concentration of total serum calcium, either corrected for albumin or not, could predict critically high or low values in critical illness. Methods This report describes a retrospective study using the Medical Information Mart for Intensive Care (MIMIC) III database. Test panels that contained serum albumin, total calcium, and ionized calcium (named ATI panels) with order time intervals of less than one hour were extracted. The predictive accuracy of total calcium, either corrected for albumin or not, was assessed using receiver operating characteristic (ROC) curve analysis. Results A total of 12 118 ATIs with 103 critically low and 92 critically high ionized calcium results were extracted. The areas under ROC curves (AUCs) of corrected and uncorrected total calcium for predicting critically low ionized calcium were 0.69 (95% CI: 0.61-0.76) and 0.70 (95% CI: 0.63-0.78), respectively. For predicting critically high ionized calcium, the AUCs were 0.98 (95% CI: 0.97-1.00) and 0.97 (95% CI: 0.95-1.00), respectively. With positive predictive values (PPVs) of 0.05 and 0.10, the sensitivities (both corrected and uncorrected) were approximately 0.50 for predicting critically low ionized calcium and 0.95 for predicting critically high ionized calcium. Conclusions Total calcium, either corrected for albumin or not, is not a reliable test to predict critically low ionized calcium in critical illness. Total calcium's predictive accuracy for critically high ionized calcium is high.

Early detection of the health lesions induced by chronic arsenic exposure (HLICAE) are crucial to prevent permanent arsenic-induced damage. If HLICAE can be identified in time, appropriate preventive and therapeutic measures may be provided without various avoidable lesions. The present study aims to assess the probability of HLICAE early recognition with metabolomics. Applying a case-control study, 94 participants with HLICAE (cases) and other 94 subjects without HLICAE (controls) were matched with gender and age (±1 year), coming from a previous chronic arsenic exposure cohort. Serum metabolomic profiles were assessed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and analyzed with univariate and multivariate statistics. A total of 210 and 364 features were detected in positive and negative ion modes (ESI+/ESI-), respectively. The altered metabolic pathways included lipid and amino acid metabolisms. 28 metabolomics-based biomarkers were significantly associated with HLICAE and provided areas under the curve (AUC, 95% confidence interval) of 0.898 (0.836, 0.960) and 0.908 (0.855, 0.960) in the discovery phase, 78.6% and 86.4% of positive predictive values in the validation phase, in distinguishing HLICAE from controls in ESI+/ESI-, respectively. This study provides novel insights on mechanisms of health effects probably induced by chronic arsenic exposure, and these biomarkers may be applied in HLICAE early detection.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-β), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-β levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

The aim of the current study was to understand the mechanisms of apoptosis occurring in cultured human lens epithelial cells (HLECs) following ultraviolet B (UVB) irradiation. The investigations intended to confirm the presence of apoptosis and to reveal the roles of oxidative stress, calcium (Ca2+), c‑Jun NH2‑terminal kinase (JNK)1/2, and extracellular signal‑regulated kinase (ERK)1/2 signaling pathway in these progresses. Cell apoptosis, ROS generation and intracellular Ca2+ concentration was measured by flow cytometry. The expression of CALML3, caspase-3, Bax, Bcl-2, p-JNK1/2, JNK1/2, p-ERK1/2 and ERK1/2 was measured by RT-qPCR and western blot analysis. Annexin V‑fluorescein isothiocyanate/propidium iodide staining demonstrated that UVB irradiation increased the apoptotic rate, reactive oxygen species (ROS) production and intracellular Ca2+ concentration of HLECs in dose‑ and time‑dependent manners. Overexpression of calmodulin like 3 (CALML3) reversed the effects of UVB irradiation on apoptosis, ROS production and Ca2+ concentration of HLECs, and decreased expressions of caspase‑3 and Bax, with increased expressions of Bcl‑2. Notably, silencing of CALML3 had similar effects to UVB irradiation and inhibited the activation JNK1/2 and ERK1/2 pathways. Nimodipine, a Ca2+‑channel antagonist, significantly attenuated the damages induced by CALML3 downregulation. In conclusion, UVB irradiation induced increase in apoptosis, ROS production and Ca2+ concentration of HLECs, in part, by downregulating the expression of CALML3 and involved oxidative stress, Ca2+, JNK1/2 and ERK1/2 signaling pathways, suggesting that investigating CALML3 may useful for developing cataract treatment.

Previous studies have evaluated the accuracy of serum and urinary measurements of cytokeratin-19 fragment (CYFRA 21-1) for the diagnosis of bladder cancer; however, the results have been inconsistent. The aim of this study was to evaluate the overall accuracy of CYFRA 21-1 for the diagnosis of bladder cancer. We performed a search for English-language publications reporting on the detection of CYFRA21-1 levels for the diagnosis of bladder cancer through November 2, 2014, using public medical databases, including EMBASE, Web of Science, and Medline. The quality of the studies was assessed by revised QUADAS tools. The performance characteristics were pooled and analyzed using a bivariate model. Publication bias was explored with the Deek's test. Sixteen studies, with a total 1,262 bladder-cancer patients and 1,233 non-bladder-cancer patients, were included in the study. The pooled sensitivities for serum and urine CYFRA 21-1 were 0.42 (95 % confidence interval (CI), 0.33-0.51) and 0.82 (95 % CI, 0.70-0.90), respectively. The corresponding specificities were 0.94 (95 % CI, 0.90-0.96) and 0.80 (95 % CI, 0.73-0.86), respectively. The areas under the summary receiver-operating-characteristic curves for serum and urine CYFRA 21-1 were 0.88 (95 % CI, 0.85-0.91) and 0.87 (95 % CI, 0.84-0.90), respectively. The major design deficiencies of the included studies were participant-selection bias, potential review, and verification bias. Therefore, we concluded that both serum and urine CYFRA 21-1 served as efficient indexes for bladder-cancer diagnosis. Additional, well-designed studies should be performed to rigorously evaluate the diagnostic value of CYFRA 21-1 for bladder cancer.

Background: Although anti-retroviral therapy (ART) and CD4 counts before ART (CD4CBA) link to death risk of timely diagnosed HIV/AIDS patients, the role of ART and its joint effects with CD4CBA on late diagnosed HIV/AIDS participants (LDPs) remain unclear. Methods: Based on data extracted from the AIDS Prevention and Control Information System, multiple cox proportion hazardous regression models were applied to assess effects of ART and CD4CBA on the death risk of LDPs. Findings: Among 607 LDPs, the overall mortality (95% CI) for participants receiving ART was 13·48 (8·95, 18·01) per 10000 person-month and significantly lower than that of controls [468·46 (328·46, 608·46), P =120 cells/μl (median) had the lowest risk of death [AHR: 0·03; 95% CI: 0·02, 0·06; P

Background FLT3 is a member of receptor tyrosine kinase III family, mainly expressed in hematopoietic cells. The aberrant expression and function of FLT3 are strongly related to leukemia, especially acute myeloid leukemia. Its varieties of amino-acid residues mutations, such as FLT3-ITDs and -TKDs, can induce constant proliferation of hematological tumor cells with poor prognosis. Hence FLT3 serves as a promising target in AML chemotherapy. Objective This review focused on the progress of FLT3 inhibitors study including those that have entered clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful reference for the development of new anti-leukemia drugs. Method Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications were identified and classified into five categories, including quinolone-related, indole-related, ureas, pyrimidines and other compounds. Results For each category of compounds, the structural feature, SAR, biological activity and current research status were thoroughly reviewed and analyzed. Conclusion Although some of those compounds expressed potent bioactivities and have reached the advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement of the intrinsic properties of FLT3 inhibitors.

BackgroundRed blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) have been reported to be associated with outcomes of acute cerebral infarction. However, their prognostic value in patients with subarachnoid haemorrhage (SAH) remains largely unknown. The aim of this study was to investigate the prognostic value of RDW and NLR in SAH patients.MethodsMedical records of adult SAH patients admitted to intensive care unit (ICU) were extracted from Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II, version 2.6), a publicly accessible ICU database. Prognostic value of RDW and NLR was analysed using logistic regression model, Kaplan-Meier curve analysis and Cox regression model.ResultsA total of 274 SAH patients were included. Patients died in hospital had significantly higher RDW and NLR. RDW and NLR were significantly associated with hospital death, with adjusted odds ratios of 1.39 (95% CI, 1.06–1.82) and 1.04 (95% CI, 1.00–1.08), respectively. Furthermore, increased RDW and NLR were associated with higher one-year mortality, with an adjusted hazard ratio of 1.20 (95% CI, 1.02–1.41) for per 1% increased RDW and 1.03 (95% CI, 1.00–1.05) for per 1 increased NLR.ConclusionRDW and NLR are useful indices to evaluate the outcomes of ICU admitted patients with SAH.

Objective To evaluate the diagnostic performance of the mid-regional portion of the pro-atrial natriuretic peptide (MR-proANP) for heart failure (HF) in dyspnea patients. Design and methods We performed a systematic review of English-language studies published during the past three decades. The performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined by random-effects models. Results Five studies met the inclusion criteria, which included 1153 patients with HF and 1904 non-HF patients. The summary estimates for MR-proANP in HF diagnosis had a diagnostic sensitivity of 0.90 (95% confidence interval (CI), 0.88–0.92), a specificity of 0.68 (95% CI, 0.66–0.70), and a diagnostic odds ratio (DOR) of 22.89 (95% CI, 12.54–41.77). The area under the curve (AUC) and Q value for the summary receiver operating characteristic (sROC) curves were 0.88 and 0.81, respectively. Conclusion MR-proANP showed a high diagnostic accuracy for HF in dyspnea patients.

Primary biliary cirrhosis (PBC) is an autoimmune disease, characterized by antimitochondrial antibodies and autoreactive T cells causing destruction of the primary bile ducts. The molecular mechanisms regulating the autoreactive T cells remain elusive. β-Arrestins (βarr) are multifunctional signaling molecules that are crucial to T cell survival. We hypothesized that βarr plays a critical regulatory function in the autoreactive T cells of PBC patients.Patients with hepatic biliary cirrhosis (n=60) were evaluated. Cytokine expression, T cell proliferation, and transcription factors were evaluated to assess regulatory functions in autoreactive T cells from the patient.Our studies showed that expression of βarr1 was elevated significantly in T lymphocytes from patients with PBC. Moreover, the level of βarr1 mRNA positively correlated with Mayo risk score in PBC patients. Based on modulation of βarr in autoreactive T cell lines, overexpression of βarr1 increased T cell proliferation, augmented interferon production, downregulated activities of nuclear factor κB and AP-1, promoted acetylation of histone H4 in the promoter regions of CD40L, LIGHT, IL-17 and interferon-γ, while downregulating acetylation of histone H4 in the promoter regions of TRAIL, Apo2, and HDAC7A, thereby regulating expression of these genes.Our findings suggest that βarr1 contributes to the pathogenesis of PBC, having significant implications for novel therapy strategy, further providing information for investigating the mechanisms of autoimmune disease.

Primary biliary cirrhosis (PBC) is a TH1/Th17 biased autoimmune disease of the medium and small bile ducts. The role of the costimulatory TNFSF9 (4-1BBL) in PBC progress was investigated by comparing its cell surface expression in peripheral blood mononuclear cells (PBMC) by flow cytometry, its mRNA expression in PBMCs by QRT-PCR and its serum concentrations in PBC patients vs. healthy controls. The TNFSF9 expression levels were compared with Mayo risk scores, PBC stages, IL-18 serum levels, total bilirubin (TBIL), and gamma glutamyltransferase (gamma-GT). The PBC patients expressed significantly greater levels of membrane bound TNFSF9, mRNA on peripheral blood mononuclear cells (PBMC), and soluble TNFSF9 (P

Background Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are reported to be increased in various inflammation-related diseases, but their clinical significance in rheumatoid arthritis (RA) remains unclear. The aim of the present study was to explore whether NLR and PLR were candidate indices for RA disease-activity assessment. Methods The medical records of 128 RA patients and 78 healthy individuals were retrospectively reviewed. Correlations of NLR and PLR with the disease activity of RA were evaluated. Results NLR and PLR were increased significantly in RA patients. NLR was significantly positively correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Disease-Activity Score including 28 joints (DAS28) in RA patients, while PLR was positively correlated with CRP and DAS28, but not with ESR. Conclusions Both NLR and PLR values may prove to be potential indices for RA disease-activity assessment.

Transferrin (Tf), a naturally existing protein, has received considerable attention in the area of drug targeting since it is biodegradable, non-toxic, and non-immunogenic. The efficient cellular uptake of Tf shows it has potential in the delivery of anti-cancer drugs, proteins, and therapeutic genes into proliferating malignant cells that overexpress transferrin receptor (TfR). In human serum, about 30% of Tf exists in the iron-saturated form (Fe(2)-Tf) and the remainder exists as apotransferrin (apo-Tf). Understanding the uptake of apo-Tf by cells will provide key insights into studies on Tf-mediated drug delivery. In the present study, we investigated visually the transport of apo-Tf into K562 cells and its intracellular localization by laser-scanning confocal microscopy (LSCM) and flow cytometry analysis (FCA). It was found that, like Fe(2)-Tf, apo-Tf can be taken up into the cells. The process is time- and temperature-dependent, competitively inhibited by Fe(2)-Tf, and significantly abolished by pronase pretreatment. Visual evidence showed that the transport of apo-Tf into K562 cells is a TfR-mediated process. Furthermore, the investigations using optical-slicing technique demonstrated that the distribution of apo-Tf is similar to that of Fe(2)-Tf, both appearing in the perinuclear region in ball-in-bowl shape.

As staffs in clinical laboratories are not routinely involved in the management of patients, it is difficult for them to perform researches designed to explore the clinical utility of laboratory tests. Using publicly accessible clinical databases for clinical research represents an alternative way of performing studies investigating the clinical aspects of laboratory tests. Here, we introduced a freely accessible critical care database named Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II). This database contains the results of many laboratory tests and thus can be used to perform laboratory medicine research. The steps to access this database were indicated, and the structure of this database was introduced. Some tips in using this database were shared.

Background Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR. Methods Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model. Results PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT. Conclusion Both RDW and NLR are useful indices in assessing the disease activity of PM/DM.

Objective The red blood cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) are increased in various inflammation related diseases, but their clinical significance in primary Sjogren's syndrome (pSS) has not been reported. The aim of the present study was to investigate the clinical significance of RDW and NLR in pSS patients. Methods The medical records of pSS patients who were admitted to Changhai Hospital of the Second Military Medical University between April 2012 and December 2013 were retrospectively reviewed. Correlations between RDW, NLR and the patient clinical characteristics were analyzed using the Spearman approach and the multiple linear regression model. Results Fifty-two pSS patients and 58 healthy controls were enrolled. RDW and NLR were increased in pSS patients and positively correlated with the Sjogren's syndrome disease activity index (SSDAI). Conclusion RDW and NLR may prove to be useful indices to estimate pSS disease activity.

Probucol decreases and bezafibrate increases plasma high density lipoprotein-cholesterol (HDL-C) levels in humans. This study was performed to determine whether the HDL-C-lowering effects of probucol could be reversed by treatment with bezafibrate in hypercholesterolemic rabbits. Forty-nine normolipidemic Japanese White rabbits were divided into 5 groups [group 1: normal chow; group 2: 0.2% cholesterol (Ch) diet; group 3: 0.2% Ch and 1% probucol diet; group 4: 0.2% Ch and 1% bezafibrate diet; group 5: 0.2% Ch and 1% probucol plus 1% bezafibrate diet] and treated for 8 weeks. Plasma lipids, cholesteryl ester transfer protein (CETP) activity in the lipoprotein-deficient plasma fraction, CETP mRNA in liver tissue and plasma drug concentrations were investigated. Serum total cholesterol (TC) increased after the rabbits in groups 2, 3, 4 and 5 were fed Ch, but overall, no significant differences were observed in serum TC and triglyceride (TG) among these groups. Serum HDL-C levels increased (p