Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

Lysosomal K+ channel TMEM175 promotes apoptosis and aggravates symptoms of Parkinson's disease.

Lysosomes are degradative organelles and play vital roles in a variety of cellular processes. Ion channels on the lysosomal membrane are key regulators of lysosomal function. TMEM175 has been identified as a lysosomal potassium channel, but its modulation and physiological functions remain unclear. Here, we show that the apoptotic regulator Bcl-2 binds to and inhibits TMEM175 activity. Accordingly, Bcl-2 inhibitors activate the channel in a caspase-independent way. Increased TMEM175 function inhibits mitophagy, disrupts mitochondrial homeostasis, and increases production of reactive oxygen species (ROS). ROS further activates TMEM175 and thus forms a positive feedback loop to augment apoptosis. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD), knockout (KO) of TMEM175 mitigated motor impairment and dopaminergic (DA) neuron loss, suggesting that TMEM175-mediated apoptosis plays an important role in Parkinson's disease (PD). Overall, our study reveals that TMEM175 is an important regulatory site in the apoptotic signaling pathway and a potential therapeutic target for Parkinson's disease (PD).

Exploring the associations among perceived teacher emotional support, resilience, Covid-19 anxiety, and mental well-being: evidence from Chinese vocational college students.

This study aimed to examine the relations between perceived teacher emotional support, Covid-19 anxiety, resilience, and mental well-being among Chinese vocational college students during Covid-19 pandemic. A sample of Chinese vocational college students (n = 1469) were surveyed with an online questionnaire composed of Teacher Emotional Support, Covid-19 Anxiety Scale, Brief Resilience Scale and Mental Well-being in Chinese version. Path analysis was employed in the study and the results showed that teacher emotional support was an important promoter for building up mental well-being but not a buffer for Covid-19 within Chinese cultural context, and the Covid-19 anxiety was significantly and negatively related to mental well-being. Resilience hindered the incidences of Covid-19 anxiety and was a significant protector for mental well-being. Covid-19 anxiety mediated the both relations between teacher emotional support and mental well-being, and resilience and mental well-being. These findings provided practical implications for coping with psychological problems and flourishing mental well-being among Chinese vocational college students. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04112-9.

Elevated circulating pro-inflammatory low-density granulocytes in adult-onset Still's disease.

OBJECTIVES: Neutrophilia is a hallmark of adult-onset Still's disease (AOSD). This study aimed to investigate the role of a distinct subset of granulocytes, the low-density granulocytes (LDGs) in the pathogenesis of AOSD. METHODS: A total of 56 patients with AOSD were included in the study. LDGs were quantified by flow cytometry. Correlations between LDGs with disease activity and laboratory parameters were determined by Spearman's nonparametric test. The cellular sources of the pro-inflammatory cytokines in AOSD were determined by intracellular staining. RESULTS: Active AOSD patients displayed significantly higher levels of LDGs compared with inactive AOSD patients and healthy controls (HCs) (P<0.001). Circulating LDGs were significantly correlated with CRP, ESR and the modified Pouchot score in patients with AOSD (P<0.01). The levels of LDGs were significantly decreased after the active AOSD patients achieved disease remission (P=0.0391). CD14+ monocytes constituted over 90% IL-1ß+ peripheral blood mononuclear cells (PBMCs) and over 80% TNF-α+ PBMCs in both active AOSD patients and HCs, respectively. In active AOSD, CD14+ monocytes accounted for 24.6% to 75.0% of IL-6+ PBMCs, while LDGs comprised 22.8% to 72.2% of IL-6+ PBMCs. In contrast, over 90% IL-6+ PBMCs were CD14+ monocytes in HCs. A significant correlation was identified between the levels of LDGs and serum IL-6 levels in AOSD (P<0.0001). CONCLUSION: Active AOSD is associated with elevated levels of a pro-inflammatory subset of neutrophils, the LDGs that produce IL-6. Our data highlight an unappreciated role of LDGs in the aberrant innate immune responses in AOSD.

Infection of Epstein-Barr Virus is Associated with the Decrease of Helios+FoxP3+Regulatory T Cells in Active Ulcerative Colitis Patients.

Background: Loss of immune homeostasis to enteric pathogens is considered to be involved in the pathogenesis of ulcerative colitis (UC), and regulatory T cells (Tregs) are key for this immune homeostasis. Helios exhibits an important effect on regulating the suppressive function of Tregs. Epstein-Barr virus (EBV) is more commonly detected in UC. However, whether there is an association between EBV infection and Helios+Tregs and its impact on disease activity of UC remain unclear. We aimed to explore the clinical significance of Helios+Tregs and their potential association with EBV infection in UC. Methods: Seventy-six UC patients and 38 controls were consecutively enrolled. Helios+FoxP3+Tregs were analyzed using flow cytometry and compared among groups. Eight active UC patients treated with 5-aminosalicylic acid were followed up. Correlation analyses were conducted between Helios+FoxP3+Tregs and disease activity indicators. In addition, EBV viral loads in the mucosal lesion were quantified in active UC by quantitative polymerase chain reaction and were comprehensively analyzed in subgroups of different disease severity, and their associations with Helios+FoxP3+Tregs were also analyzed. Results: Helios+FoxP3+Tregs were significantly decreased in active UC and were inversely correlated with serum C-reactive protein and Mayo score. Moreover, we observed the recovery of Helios+FoxP3+Tregs in followed-up active UC achieving remission after treatment. EBV loads were higher in active UC, and levels of Helios+FoxP3+Tregs in the EBV-positive subgroup were lower than the EBV-negative subgroup in moderate and severe active patients. Most importantly, we found that Helios+FoxP3+Tregs were significantly negatively correlated with EBV viral loads. Conclusion: Helios+FoxP3+Tregs are likely to play a pivotal role in disease activity of UC and may be influenced by EBV infection.

Exposure to phthalates is associated with grip strength in US adults.

The potential association of exposure to phthalates with muscle strength was reported in previous animal experiments. However, their association was rarely directly investigated in general populations. Thus, we aimed to ascertain the association of exposure to phthalates with grip strength using cross-sectional analysis which included 2436 individuals aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) during 2011-2014. The multivariable linear regression models were performed with the adjustment of related covariates. The results suggested that a one-unit increase in log-transformed phthalate metabolites (µg/g creatinine) was inversely associated with grip strength, including Mono-(2-ethyl)-hexyl phthalate (ß: -2.727 kg, 95% CI: -3.452, -2.002), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (ß: -3.721 kg, 95% CI: -4.836, -2.607), Mono-(2-ethyl-5-oxohexl) phthalate (ß: -4.669 kg, 95% CI: -5.761, -3.577), Mono-2-ethyl-5-carboxypentyl phthalate (ß: -4.756 kg, 95% CI: -5.957, -3.554), Mono-carboxyoctyl phthalate (ß: -1.324 kg, 95% CI: -2.412, -0.235), Mono-carboxynonyl phthalate (ß: -2.036 kg, 95% CI: -3.185, -0.886), Mono-benzyl phthalate (ß: -2.940 kg, 95% CI: -3.853, -2.026), Mono-n-butyl phthalate (ß: -2.100 kg, 95% CI: -3.474, -0.726), Mono-isobutyl phthalate (ß: -2.982 kg, 95% CI: -4.331, -1.633), and Mono-ethyl phthalate (ß: -1.709 kg, 95% CI: -2.368, -1.050). In subgroup analyses, the associations remained largely unchanged when the samples were stratified by gender and age; However they became ambiguous among underweight subjects when the samples were stratified by BMI status. Overall, exposure to phthalates was inversely associated with grip strength among US adults, regardless of their genders and ages. The suggestive potential BMI status-specific effects of phthalates on grip strength were observed.

Upregulated IL-17A secretion and CCR6 co-expression in Treg subsets are related to the imbalance of Treg/Th17 cells in active UC patients.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease, which is characterized with overactive immune response. It is well established that the imbalance between Tregs and Th17 cells plays a pivotal role in pathogenesis of UC. In this study, we investigated the impact of functional changes in Treg subsets on Treg/Th17 ratio and further explored their clinical significance in the activity of UC. Treg subsets were comprehensively analysed using flow cytometry and in vitro cultured in both active and remission UC patients, of which nine active UC patients were further followed up. The correlation analyses were performed to explore the potential associations between Treg subsets and clinical indicators, as well as the impact of serum cytokines, detected by ELISA, on IL-17A secretion and CCR6 co-expression of Treg subsets. In active UC patients, we found CD45RA- FoxP3hi Tregs were obviously decreased and inversely correlated with disease activity, while CD45RA+ FoxP3lo Tregs were increased and positively correlated with disease activity. Meanwhile, IL-17A secretion and CCR6 co-expression levels in Tregs were significantly increased in active UC. Moreover, Tregs co-expressing CCR6 possesses higher level of IL-17A secretion. In nine followed up patients, we observed downregulated IL-17A secreting and CCR6 co-expression when achieving remission from active stage. In addition, IL-17A+ FoxP3+ and IL-17A+ FoxP3+ CCR6+ Tregs were positively correlated with serum IL-21 and disease activity, respectively. These findings suggested that upregulated IL-17A secretion and CCR6 co-expression in Treg subsets may be related to the imbalance between Tregs and Th17 cells and associated with the disease activity in UC patients.

Associations of urinary levels of phenols and parabens with osteoarthritis among US adults in NHANES 2005-2014.

Phenols and parabens are two major classes of endocrine-disrupting compounds (EDCs) that may be related to multiple human diseases. However, there has been no studies examining the association between phenols as well as parabens and osteoarthritis (OA). We assessed the link between urinary concentrations of triclosan (TCS), benzophenone-3 (BP-3), bisphenol A (BPA), and parabens with OA based on the data collected from National Health and Nutrition Examination Survey in multivariable logistic regression models. Among all the 7114 participants included, the weighted percentage of OA was 12.11% (n = 807). Compared with participants at tertile 1, those at tertile 2 of urinary BP-3, and tertile 3 of urinary BP-3 were more likely to show increased OA prevalence in a fully adjusted model, with odd ratio (OR) as 1.34 [95% confidence interval (CI): 1.01-1.78], 1.55 (95 CI%: 1.17-2.06), and 1.66 (95 CI%: 1.23-2.24), respectively. In subgroup analyses stratified by potential confounders, various subgroups remained to show statistically significant positive association between urinary BP-3 and OA prevalence. Otherwise, we observed no statistically significant associations between urinary TCS, BPA or parabens with OA. In conclusion, this serves as the first study in which we found that the urinary concentration of BP-3 was positively correlated to prevalence of OA among the US population.

Relationship between urinary bisphenol a levels and cardiovascular diseases in the U.S. adult population, 2003-2014.

BACKGROUND: Emerging evidence has identified cardiovascular system as a potential target of Bisphenol A (BPA). Although a few studies have revealed the relationship between BPA and the risk of several cardiovascular diseases (CVD) outcomes and CVD risk factors, no published studies have investigated the link between urinary BPA and the risk of stroke. METHODS: Data were derived from the United States National Health and Nutrition Examination Surveys (NHANES), with a representative sample aged ≥20 years (n = 9139) from 2003 to 2014. We performed multivariable logistic regression model to estimate associations between quartiles and natural logarithm transformed urinary BPA concentrations and five specific CVD outcomes and total CVD. RESULTS: In quartile analysis, highest level of urinary BPA was associated with increased prevalence of myocardial infarction (MI) (OR = 1.73, 95% CI = 1.11-2.69) and stroke (OR = 1.61, 95% CI = 1.09-2.36), when compared with those at the lowest quartile. Per unit (µg/g creatinine) increment in ln-transformed BPA concentration was shown to be significantly associated with 19%, 19%, 25%, 29%, 20%, and 16% increased odds ratios of prevalence of congestive heart failure, coronary heart disease (CHD), angina pectoris, MI, stroke and total CVD among total participants, respectively. Similar associations were found in males rather than in females. CONCLUSION: We provided the premier evidence of positive relationship between urinary BPA concentration and stroke in U.S. POPULATION: Urinary BPA levels were also positively correlated with congestive heart failure, CHD, angina pectoris, MI, as well as total CVD. These associations were more evident in males. Well-coordinated and prospective studies are warranted to gain the human effects of BPA on CVD.

Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer.

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

Inhibition of lysosomal TRPML1 channel eliminates breast cancer stem cells by triggering ferroptosis.

Cancer stem cells (CSCs) are a sub-population of cells possessing high tumorigenic potential, which contribute to therapeutic resistance, metastasis and recurrence. Eradication of CSCs is widely recognized as a crucial factor in improving patient prognosis, yet the effective targeting of these cells remains a major challenge. Here, we show that the lysosomal cation channel TRPML1 represents a promising target for CSCs. TRPML1 is highly expressed in breast cancer cells and exhibits sensitivity to salinomycin, a drug known to selectively eliminate CSCs. Pharmacological inhibition and genetic depletion of TRPML1 promote ferroptosis in breast CSCs, reduce their stemness, and enhance the sensitivity of breast cancer cells to chemotherapy drug doxorubicin. The inhibition and knockout of TRPML1 also demonstrate significant suppression of tumor formation and growth in the mouse xenograft model. These findings suggest that targeting TRPML1 to eliminate CSCs may be an effective strategy for the treatment of breast cancer.

Loss of mucosal tolerance to glycoprotein 2 isoform 1 is a potential novel diagnostic biomarker for cholangiocarcinoma.

BACKGROUND: Anti-glycoprotein 2 (anti-GP2) IgA and antineutrophil-cytoplasmic antibodies to proteinase 3 (PR3-ANCA) have been reported as predictive markers of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC), but their prevalence in CCA patients without PSC remains unclear. METHODS: This study involved Asian discovery (n = 118) and European validation (n = 38) cohorts of CCA patients without PSC, alongside 49 Asian and 82 European pancreatic ductal adenocarcinoma (PDAC) patients, 21 with benign pancreatic neoplasms (BPN) and 45 with hepatocellular carcinoma (HCC), and 157 healthy controls (HC) from Asia and Europe. We analyzed the prevalence of PR3-ANCA, IgA and IgG against GP21 and GP24, and the CA19-9 levels. RESULTS: Anti-GP21 IgA was the most prevalent in both CCA cohorts (discovery: 55.1 %; validation: 42.1 %) and significantly higher than in other groups except PDAC (all p < 0.05). It demonstrated the best diagnostic performance in distinguishing CCA from disease controls and HC, outperforming tumor markers. No significant correlation was found between anti-GP21 IgA levels and CA19-9 levels. CONCLUSION: Our findings show that anti-GP21 IgA revealing the loss of mucosal tolerance is a potential novel diagnostic biomarker for CCA.

Predicting effects of career adaptability and educational identity on the career decision-making of Chinese higher vocational students.

The present study aimed to explore factors affecting Chinese higher vocational students' career decision-making. A sample (N = 983) was surveyed with a questionnaire. The results showed that somewhat more than half of the students (57.4%) decided to apply for a bachelor's degree whereas the rest decided to work (22.4%) or undecided (20.2%). Academic performance, grade, gender, study major, and career adaptability were shown to predict decision-making. By contrast, educational identity did not predict participants' career decision-making. These findings imply that career education should be based on students' choices for future development.

Prédiction des effets de l'adaptabilité professionnelle et de l'identité éducative sur la prise de décision professionnelle des étudiants professionnels supérieurs chinois. La présente étude visait à explorer les facteurs qui influent sur les décisions de carrière des étudiants professionnels chinois de niveau supérieur. Un échantillon (N = 983) a été sondé au moyen d'un questionnaire. Les résultats ont montré qu'un peu plus de la moitié des étudiants (57,4%) ont décidé de demander une licence, tandis que le reste a décidé de travailler (22,4%) ou indécis (20,2%). Le rendement scolaire, la note, le sexe, les études majeures et l'adaptabilité à la carrière ont permis de prédire la prise de décisions. En revanche, l'identité éducative n'a pas prédit la prise de décisions professionnelles des participants. Ces résultats impliquent que la formation professionnelle devrait être basée sur les choix des étudiants pour leur développement futur.

Predicción de los efectos de la adaptabilidad profesional y la identidad educativa en la toma de decisiones sobre la carrera de los estudiantes de formación profesional superior chinos. El objetivo del presente estudio es explorar los factores que afectan a la toma de decisiones sobre la carrera profesional de los estudiantes chinos. Se encuestó una muestra (N = 983) con un cuestionario. Los resultados mostraron que algo más de la mitad de los estudiantes (57,4%) decidieron solicitar una licenciatura, mientras que el resto decidió trabajar (22,4%) o indeciso (20,2%). Se demostró que el rendimiento académico, la calificación, el género, la especialización y la adaptabilidad profesional predecían la toma de decisiones. Por el contrario, la identidad educativa no predijo la toma de decisiones profesionales de los participantes. Estos hallazgos implican que la educación profesional debe basarse en las opciones de los estudiantes para el desarrollo futuro.

How physical exercise influences academic burnout among Chinese "Double Non" college students: the chain mediation role of mobile phone addiction and learning engagement.

Background: With mental anxiety caused by the COVID-19 pandemic, the trend of "lying down" has become increasingly prevalent among Chinese college students such as not thinking ahead, decadent abandonment, and being weak daily. Particularly, Chinese "Double Non" college students are more likely to face academic burnout (AB) due to lower school satisfaction and after-degree employment ratio, in comparison to "Double First-Class" college students. Objectives: In view of this, the present study examined the structural relationships of physical exercise (PE), mobile phone addiction (MPA), learning engagement (LE), and AB among Chinese "Double Non" college students, aiming at exploring corresponding mechanism to provide supportive guidance for alleviating potential AB. Methods: This study adopted a cross-sectional survey approach among the sample of "Double Non" college students in China. We recruited 930 participants (272 men and 658 women) in the second half of the 2022-2023 academic year, all of whom completed questionnaires involving Physical Exercise Rating Scale, Mobile Phone Dependence Index Scale, Utrecht Work Engagement Scale-Student, and Maslach Burnout Inventory-Student Survey. A series of statistical analyses, including descriptive statistics, bivariate correlations, and direct and indirect effects among study variables, were proceeded based on the collected data. Results: The results showed that PE can not only directly and negatively influence AB, but also indirectly and negatively influence AB through the mediation of MPA as well as the chain mediation of both MPA and LE. While PE had no significantly indirect effect on AB via LE. Discussion: Physical exercise was proved to be an effective way to reduce MPA and then enhance LE, consequently leading to decreased AB in Chinese "Double Non" college students. The findings were discussed in light of related research, and implications and future directions were put forward for application in potential theoretical research and educational practice.

The gender-specific adverse association of polycyclic aromatic hydrocarbons on skeletal muscle mass and strength in the general adults and the possible mechanisms in experimental rats.

Whether polycyclic aromatic hydrocarbons (PAHs) exposure is associated with muscle mass and muscle strength has been scantly investigated. The cross-sectional associations of urinary PAH metabolites with appendicular skeletal muscle mass and hand grip strength in adults were first investigated in the National Health and Nutrition Examination Survey (NHANES). Laboratory study was further carried out to examine the effect of PAHs on skeletal muscle mass and strength. 2742 and 2462 US adults were finally analyzed for muscle mass and muscle strength, respectively. In male participants, urinary PAH metabolites were found to show an inverse relationship with muscle mass and grip strength. In female participants, no significant relationship was found between urinary PAH metabolites with muscle mass or grip strength. In male Sprague-Dawley (SD) rats, administration of B [a]P induced muscle atrophy when compared with the control. However, muscle mass and strength were not significantly altered in female rats. The variations in muscle morphology parameters were accompanied by significant decrease in plasma testosterone levels in the B [a]P-treated male rats. Testosterone co-treatment significantly mitigated B [a]P mediated damages in skeletal muscle in male rats. The results of the present study indicate that there may be a gender-specific causal relationship between the PAHs and muscle atrophy.

Association of a novel antisense lncRNA TP73-AS1 polymorphisms and expression with colorectal cancer susceptibility and prognosis.

BACKGROUND: TP73-AS1 is a novel antisense long noncoding RNA and plays an important role in cell proliferation and cancer development. However, the link between TP73-AS1 and colorectal cancer (CRC) has not yet been reported. OBJECTIVE: To explore the association of genetic variants in TP73-AS1 and its expression with CRC susceptibility and prognosis. METHODS: A case-control study (including 507 CRC cases and 503 controls) and bioinformatics analysis were conducted. RESULTS: rs9800 polymorphism was significantly related to higher risk in CRC [adjusted odds ratio (AOR) = 1.33, 95% confidence interval (CI) = 1.02-1.75, P = 0.034 in heterozygote codominant model]. There was no difference between TP73-AS1 polymorphisms and different tumor node metastasis (TNM) stages in the adjusted model. Moreover, TP73-AS1 expression level was positively related to different TNM stages. After adjusted for age, gender and TNM, higher TP73-AS1 expression levels were related to shorter recurrence-free survival time [hazard ratio (HR) = 1.66, 95% CI = 1.02-2.71, P = 0.043]. CONCLUSION: TP73-AS1 polymorphisms and expression may be associated with susceptibility and prognosis of CRC.

Elevated Granulocyte Colony-stimulating Factor Levels in Patients With Active Phase of Adult-onset Still Disease.

OBJECTIVE: Neutrophilia is a hallmark of adult-onset Still disease (AOSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AOSD. METHODS: Sera were collected from 70 patients with AOSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory variables, and LDG levels in patients with AOSD were analyzed by Spearman correlation test. RESULTS: Patients with active AOSD presented significantly higher levels of G-CSF compared to inactive AOSD patients (P < 0.001) and HCs (P < 0.0001). The G-CSF levels were significantly decreased after active AOSD patients achieved disease remission (P = 0.0015). The G-CSF levels were significantly correlated with C-reactive protein, erythrocyte sedimentation rate, ferritin, and systemic score in AOSD (P < 0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (P < 0.0001), neutrophil-to-lymphocyte ratio (P < 0.0001), percentages of LDGs in the peripheral blood mononuclear cells (P = 0.004), as well as absolute numbers of circulating LDGs (P = 0.018) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy, or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (P < 0.05). CONCLUSION: Our findings indicate that G-CSF is implicated in the pathogenesis of AOSD, and targeting G-CSF may have therapeutic potential for AOSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study.

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk. Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses. Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): -0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88-1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (ß: 0.007, 95% CI: -0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results. Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.

Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis.

Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA). Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer. Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001). Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).

Association of urinary phthalate metabolites with osteoarthritis in American adults: Results from the national health and nutrition examination survey 2003-2014.

Phthalates have extensive existence in the living environment of human, probably tightly associated with multiple human diseases. The present study aimed to exploratorily investigate the association of urinary phthalate metabolites with osteoarthritis (OA) in American adults by exploiting the data extracted from National Health and Nutrition Examination Survey (NHANES) 2003-2014 with levels of eleven urinary phthalate metabolites as exposure. The multivariable logistic regression models were performed after controlling for urinary creatinine, age, gender, race/ethnicity, education level, marital status, smoking, body mass index, physical activity in recreational time, family poverty income ratio, diabetes, hypertension, as well as survey cycle. Compared with those in the lowest quantile, we observed higher prevalence of OA in the maximal quantile of MCOP (OR = 1.55, 95% CI = 1.06-2.27) in adjusted model. A one-unit increase in log-transformed phthalate metabolites was significantly associated with higher OA prevalence, including MCOP (OR = 1.13, 95% CI = 1.02-1.26) and MBzP (OR = 1.12, 95% CI = 1.00-1.26) in adjusted model. In subgroup analysis, the positive associations between phthalate metabolites and OA prevalence remained robust both in males and females. In brief, this study first presented positive evidence for the association of urinary level of phthalate metabolites with OA prevalence in American adults. Additional causal research is required to confirm the finding from our analysis and elucidate the potential underlying mechanisms of phthalates exposure on OA.