Antineutrophil cytoplasmic antibody is an independent risk factor in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients. RESULTS: The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown. CONCLUSIONS: The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.

Manure replacing synthetic fertilizer improves crop yield sustainability and reduces carbon footprint under winter wheat-summer maize cropping system.

Manure replacing synthetic fertilizer is a viable practice to ensure crop yield and increase soil organic carbon (SOC), but its impact on greenhouse gas (GHG) emissions is inconsistent, thus remains its effect on CF unclear. In this study, a 7-year field experiment was conducted to assess the impact of replacing synthetic fertilizer with manure on crop productivity, SOC sequestration, GHG emissions and crop CF under winter wheat-summer maize cropping system. Five treatments were involved: synthetic nitrogen, phosphorus, and potassium fertilizer (NPK) and 25%, 50%, 75%, and 100% of manure replacing synthetic N (25%M, 50%M, 75%M, and 100%M). Compared with NPK treatment, 25%M and 50%M treatments maintained annual yield (winter wheat plus summer maize) and sustainable yield index (SYI), but 75%M and 100%M treatments significantly decreased annual yield, and 100%M treatment also significantly reduced annual SYI. The SOC content exhibited a significant increasing trend over years in all treatments. After 7 years, SOC storage in manure treatments increased by 3.06-11.82 Mg ha-1 relative to NPK treatment. Manure treatments reduced annual GHG emissions by 14%-60% over NPK treatment. The CF of the cropping system ranged from 0.16 to 0.39 kg CO2 eq kg-1 of grain without considering SOC sequestration, in which the CF of manure treatments lowered by 18%-58% relative to NPK treatment. When SOC sequestration was involved in, the CF varied from -0.39 to 0.37 kg CO2 eq kg-1 of grain, manure treatments significantly reduced the CF by 22%-208% over NPK treatment. It was concluded that replacing 50% of synthetic fertilizer with manure was a sound option for achieving high crop yield and SYI but low CF under the tested cropping system.

The peptide GOLVEN10 alters root development and noduletaxis in Medicago truncatula.

The conservation of GOLVEN (GLV)/ROOT MERISTEM GROWTH FACTOR (RGF) peptide encoding genes across plant genomes capable of forming roots or root-like structures underscores their potential significance in the terrestrial adaptation of plants. This study investigates the function and role of GOLVEN peptide-coding genes in Medicago truncatula. Five out of fifteen GLV/RGF genes were notably upregulated during nodule organogenesis and were differentially responsive to nitrogen deficiency and auxin treatment. Specifically, the expression of MtGLV9 and MtGLV10 at nodule initiation sites was contingent upon the NODULE INCEPTION transcription factor. Overexpression of these five nodule-induced GLV genes in hairy roots of M. truncatula and application of their synthetic peptide analogues led to a decrease in nodule count by 25-50%. Uniquely, the GOLVEN10 peptide altered the positioning of the first formed lateral root and nodule on the primary root axis, an observation we term 'noduletaxis'; this decreased the length of the lateral organ formation zone on roots. Histological section of roots treated with synthetic GOLVEN10 peptide revealed an increased cell number within the root cortical cell layers without a corresponding increase in cell length, leading to an elongation of the root likely introducing a spatiotemporal delay in organ formation. At the transcription level, the GOLVEN10 peptide suppressed expression of microtubule-related genes and exerted its effects by changing expression of a large subset of Auxin responsive genes. These findings advance our understanding of the molecular mechanisms by which GOLVEN peptides modulate root morphology, nodule ontogeny, and interactions with key transcriptional pathways.

ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han.

AIMS: Aimed to identify a new susceptibility gene associated with primary biliary cholangitis (PBC) in Chinese Han and investigate the possible mechanism of that gene in PBC. METHODS: A total of 466 PBC and 694 healthy controls (HC) were included in our study, and genotyping GTF2I gene variants by Sequenom. CD19 + B cells were isolated for Chromatin immunoprecipitation sequencing (ChIP-seq). Additionally, MEME-ChIP was utilized to perform searches for known motifs and de novo motif discovery. The GTF2I ChIP-seq of hematopoietic cell line (K562) results were obtained from ENCODE (GSE176987, GSE177691). The Genomic HyperBrowser was used to determine overlap and hierarchal clustering between ours and ENCODE datasets. RESULTS: The frequency of the rs117026326 variant T allele was significantly higher in PBC patients than that in HC (20.26% compared with 13.89%, Pc = 1.09E-04). Furthermore, we observed an elevated proportion of GTF2I binding site located in the upstream and 5' UTR of genes in PBC in comparison with HC. Additionally, an in-depth analysis of IL21R region revealed that GTF2I might bind to the IL21R promoter to regulate the expression of the IL21R, with four peaks of GTF2I binding sites, including three increased binding sites in upstream, one increased binding site in 5' UTR. Motif analysis by MEME-ChIP uncovered five significant motifs. A significant overlap between our ChIP and GSE176987, GSE17769 were found by the Genomic HyperBroswer. CONCLUSIONS: Our study confirmed that GTF2I was associated with PBC in Chinese Han. Furthermore, our gene function analysis indicated that IL21R may be the target gene regulated by GTF2I.

Prevalence and genotype distribution of human papillomavirus infection among female outpatients in Northeast China: a population-based survey of 110,927 women.

PURPOSE: Human papillomavirus (HPV) infection, especially high-risk HPV, is a major etiological factor for cervical cancer. This study aimed to investigate the distribution of human papillomavirus infection among female outpatients in Northeast China. METHODS: A total of 110,927 women aged between 18 and 80 years from Shengjing Hospital of China Medical University, tested with the HPV Geno-Array Test Kit (HybriBio), were enrolled in this study. RESULTS: The overall prevalence of HPV infection in the study population was 16.95% (18,802/110,927). A total of 21 HPV genotypes were identified and the six most prevalent ones were HPV16 (5.78%), HPV58 (2.62%), HPV52 (1.91%), HPV33 (1.55%), HPV53 (1.45%), and HPV18 (1.16%). The prevalence of single HPV was 83.58% (15,714/18802) and that of multiple HPV was 16.42% (3088/18802). HPV16, HPV58, and HPV52 were the most common types of HR-HPV infections, while CP8304, HPV11, and HPV6 were the most common types of LR-HPV infections. Among the multiple infection groups, HPV16 was the most common type of co-infection. Furthermore, the prevalence of HPV infections varied among different age groups. Age-specific prevalence of HPV exhibited two peaks in the youngest age group and in the group aged 50-60 years. CONCLUSION: HPV16, 58, 52, 33, 53, and 18 were the most common types in the general female population. The prevalence of HPV infection varied among different age groups. This study provides guidance for future HPV-based cervical cancer screening tests and prophylactic HPV vaccinations in China.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

Objective: We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. Methods: This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. Results: In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). Conclusions: LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjögren's syndrome.

OBJECTIVE: Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles in primary Sjögren's syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in pSS. METHODS: pSS patients were enrolled and NETosis markers were measured in plasma and labial glands using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (MitoSOX) production, and JC-1 were measured by flow cytometry. RESULTS: NETosis markers including cell-free DNA (cf-DNA) and myeloperoxidase (MPO) in plasma and labial glands from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated type I IFN signaling pathway and higher expression of genes related to type I interferon in pSS neutrophils. Further stimulating with IFN-α 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils. CONCLUSIONS: Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.

Safety and Efficacy of PD-1/PD-L1 Inhibitors in Cancer Patients With Preexisting Autoantibodies.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood. Methods: The present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed. Results: 67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS. Conclusions: The presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

AC-X: Characteristic Antinuclear Antibody Patterns of Two Anti-Mi-2 Autoantibody-Positive Dermatomyositis Patients-A Case Report.

Here we reported two anti-Mi-2 autoantibody-positive dermatomyositis (DM) patients with a characteristic antinuclear antibody (ANA) immunofluorescence pattern. Autoantibodes were screened by indirect immunofluorescence (IIF) on HEp-2 cells (Euroimmun, Lübeck, Germany) and confirmed by line immunoblot (ANA Profile 3-Euroimmun, Germany). These two patients were positive for ANA (speckled, titer 1:320), followed by confirmation of positive anti-Mi-2α and anti-Mi-2ß positive and negative for all other antibodies. We found a characteristic ANA pattern of the anti-Mi-2 antibody that differed from the AC-4 pattern, especially in the morphology of mitotic cells (metaphase, anaphase, and telophase). Thus, we would like to suggest reporting this characteristic antinuclear antibody pattern as a new AC type, as AC-X.

Low vitamin D concentrations and BMI are causal factors for primary biliary cholangitis: A mendelian randomization study.

Backgrounds: Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC. Methods: The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results. Results: Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77; p=0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84; p=0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries. Conclusion: Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.

Expression patterns of long non-coding RNAs in peripheral blood mononuclear cells of non-segmental vitiligo.

OBJECTIVE: We explored the patterns of long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from patients with non-segmental vitiligo. METHODS: We used high-throughput RNA sequencing technology to generate sequence data from five patients with non-segmental vitiligo alongside five normal healthy individuals, and then performed bioinformatics analyses to detect the differential expression of lncRNA in PBMCs. Gene Ontology (GO) and pathway analyses were performed for functional annotation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify gene expression. Target miRNAs and mRNAs of differentially expressed lncRNAs were predicted using bioinformatics analysis. RESULTS: A total of 292 lncRNAs were differentially expressed in non-segmental vitiligo (fold change ≥ 2.0, P < .05), of which 171 were upregulated and 121 were downregulated. Six differentially expressed lncRNAs were selected, namely ENST00000460164.1, ENST00000393264.2, NR-046211.1, NR-135491.1, NR-135320.1, and ENST00000381108.3, for validation by qRT-PCR. The results showed that ENST00000460164.1 and NR-046211.1 were highly expressed in PBMCs of non-segmental vitiligo. An lncRNA-miRNA-mRNA network containing two lncRNAs, 17 miRNAs, and 223 mRNAs was constructed. CONCLUSION: Our results revealed patterns of differentially expressed lncRNAs in the PBMCs of non-segmental vitiligo individuals. ENST00000460164.1, and NR-046211.1 may be potential biomarkers and drug targets for the treatment of non-segmental vitiligo.

A Five-Gene Expression Signature Predicts Ovarian Cancer Metastasis.

Ovarian cancer represents one of the most malignant gynecological tumors. Despite recent advances in treatment, ovarian cancer remains to be highly susceptible to metastasis. However, information concerning genome-wide gene expression profiles is limited to develop a metastasis-specific gene signature in ovarian cancer. In this work, we try to identify changes in gene expression profile that underlie ovarian cancer metastasis. The dataset GSE73168 deposited in the Gene Expression Omnibus (GEO) database was processed to identify differentially expressed genes (DEGs) between primary tumor and metastatic tumor samples. The weighted gene correlation network analysis (WGCNA) was conducted for modules related to ovarian cancer metastasis. Modular genes associated with ovarian cancer metastasis were summarized for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Receiver operating characteristic (ROC) curves were plotted to estimate the superiority of candidate genes in detecting ovarian cancer metastasis. The WGCNA yielded 25 co-expression network modules in the dataset GSE73168, and highly correlated genes with ovarian cancer metastasis were identified in the blue module. Twenty-two genes demonstrated differential expression between primary tumor and metastatic tumor samples, and two downregulated genes (P2RY13 and NKX6-1) and three upregulated genes (CD36, LOC57399 and RP11-587D21.4) of these 22 DEGs was also shown to correlate with ovarian cancer metastasis in the blue module. The area under the ROC curve verified these five DEGs as metastasis-specific genes for ovarian cancer. These results show P2RY13, NKX6-1, CD36, LOC57399 and RP11-587D21.4 serve as metastasis-specific genes for ovarian cancer.

The association of different serum IgG4 levels with distinct clinical characteristics and treatment efficacy in patients with IgG4-related disease.

OBJECTIVSE: To explore the clinical characteristics and treatment efficacy of IgG4-related disease (IgG4-RD) patients with different levels of serum IgG4. METHODS: A total of 299 patients newly diagnosed with IgG4-RD were enrolled in this study. Patients were classified into four groups according to baseline serum IgG4 levels: Group A: normal concentration; Group B: > normal but <2× the upper reference limit (URL); Group C: between 2× and 5× the URL; Group D: >5× the URL. All patients were followed up for 12 months. The patients' clinical characteristics, laboratory parameters, plasmablasts/plasma cells and treatment efficacy were analysed. RESULTS: IgG4-RD patients with higher serum IgG4 levels had higher percentages of dacryoadenitis, sialadenitis, and autoimmune pancreatitis and a higher prevalence of allergy history, whereas patients with retroperitoneum and mediastinum lesions usually had lower serum IgG4 levels. In addition, the serum IgG4 re-elevation rate in Group D (19.4%) was higher than those in Group B (4.9%) and Group C (7.7%) (p=0.003 and p=0.020, respectively). Patients suffered fewer clinical relapses with a serum IgG4 reduction ≥50% of baseline serum IgG4 in Group B and ≥40% of baseline serum IgG4 in Group D (p=0.019 and p=0.043, respectively). In addition, the rate of clinical relapse in patients who received combination therapy with glucocorticoids and mycophenolate mofetil was 18.75% in Group D, which was higher than the rates in Groups B and C (0) (p=0.027). CONCLUSIONS: IgG4-RD patients with different levels of serum IgG4 exhibit different clinical characteristics and treatment responses.

Partial-film mulch returns the same gains in yield and water use efficiency as full-film mulch with reduced cost and lower pollution: a meta-analysis.

BACKGROUND: Plastic film mulch is widely used to improve crop yield and water use efficiency (WUE, yield per unit evapotranspiration) in semi-arid regions. It is commonly applied as partial-film mulch (PM: at least 50% soil cover) or full-film mulch (FM: complete soil cover). The PM has lower economic and environmental cost; hence it would be a superior technology provided it delivers similar gains in yield and WUE in relation to FM. RESULTS: To solve contradictory results from individual studies, we compared FM and PM in a meta-analysis of 100 studies with 1881 comparisons (685 for wheat; 1196 for maize). Compared with bare ground, FM and PM both increased yield of wheat (20-26%) and maize (37-52%), and WUE of wheat (16-20%) and maize (38-48%), with statistically undistinguishable differences between PM and FM. The increases in crop yield and WUE were stronger at elevation > 1000 m, with annual precipitation<400 mm, and on loess soil, especially for maize. CONCLUSIONS: We concluded that partial-film mulch could replace full-film mulch to return similar yield and WUE improvement, with reduced cost and environmental pollution. © 2021 Society of Chemical Industry.

Application of Synthetic Peptide CEP1 Increases Nutrient Uptake Rates Along Plant Roots.

The root system of a plant provides vital functions including resource uptake, storage, and anchorage in soil. The uptake of macro-nutrients like nitrogen (N), phosphorus (P), potassium (K), and sulphur (S) from the soil is critical for plant growth and development. Small signaling peptide (SSP) hormones are best known as potent regulators of plant growth and development with a few also known to have specialized roles in macronutrient utilization. Here we describe a high throughput phenotyping platform for testing SSP effects on root uptake of multiple nutrients. The SSP, CEP1 (C-TERMINALLY ENCODED PEPTIDE) enhanced nitrate uptake rate per unit root length in Medicago truncatula plants deprived of N in the high-affinity transport range. Single structural variants of M. truncatula and Arabidopsis thaliana specific CEP1 peptides, MtCEP1D1:hyp4,11 and AtCEP1:hyp4,11, enhanced uptake not only of nitrate, but also phosphate and sulfate in both model plant species. Transcriptome analysis of Medicago roots treated with different MtCEP1 encoded peptide domains revealed that hundreds of genes respond to these peptides, including several nitrate transporters and a sulfate transporter that may mediate the uptake of these macronutrients downstream of CEP1 signaling. Likewise, several putative signaling pathway genes including LEUCINE-RICH REPEAT RECPTOR-LIKE KINASES and Myb domain containing transcription factors, were induced in roots by CEP1 treatment. Thus, a scalable method has been developed for screening synthetic peptides of potential use in agriculture, with CEP1 shown to be one such peptide.

Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2.

PURPOSE: Circular RNAs (circRNAs) constitute a class of regulatory RNAs that are thought to play important roles in tumor initiation and progression. Several studies have reported that circRNAs may be involved in various biological processes via networks of competing endogenous RNAs (ceRNAs). However, the regulatory roles and underlying mechanisms of circRNAs in cervical cancer (CC) still largely remain to be resolved. METHODS: CircNFATC3 (hsa_circ_0005615) expression was assessed in CC cell lines (SiHa, H8) using circRNA microarray analysis, whereas qRT-PCR was used to detect circNFATC3 and miR-9-5p expression in primary human CC tissues and cell lines. The tumor promoting role of circNFATC3 was verified in CC cells using a series of functional assays, and interactions between circNFATC3, miR-9-5p and syndecan-2 (SDC2) were investigated using dual-luciferase reporter assays. SDC2 protein expression was detected using Western blotting and immunohistochemistry. The tumor promoting role of circNFATC3 was confirmed in vivo using a CC xenograft model. RESULTS: We found that circNFATC3 expression was upregulated in primary CC tissues and positively correlated with CC tumor size and stromal invasion. In addition, we found that exogenous circNFATC3 overexpression enhanced the proliferation, migration and invasion of HeLa cells, while its knockdown reduced the malignancy of SiHa cells. We also found that circNFATC3 may act directly as a miR-9-5p sponge to regulate SDC2 expression and its downstream signaling pathways, thereby enhancing CC development. CONCLUSION: Our data indicate that circNFATC3 sponges miR-9-5p to regulate SDC2 expression and, thereby, to promote CC tumor development.

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.

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

IMPORTANCE: Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program. OBJECTIVE: To evaluate hrHPV testing as a new screening modality for the national program. DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated. INTERVENTIONS: At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. MAIN OUTCOMES AND MEASURES: The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. RESULTS: A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.

Elevated Serum IgG4 Was Found in Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: The aim was to determine the levels and clinical impact of immunoglobulin G4 (IgG4) and other IgG subclasses in a Chinese population with eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We enrolled 49 patients who had EGPA, 27 who had granulomatosis with polyangiitis (GPA), 31 who had microscopic polyangiitis (MPA), and 30 healthy controls (HCs). Serum IgG subclasses were measured using commercial immunonephelometric assays and compared among different groups. RESULTS: Fifteen EGPA patients (30.61%) had elevated IgG4 levels, based on a cutoff value of 135 mg/dL. In addition, 2 GPA patients (7.40%) and 1 MPA patient (3.33%) had elevated IgG4 levels. The EPGA group had a higher IgG4 level (65.60 mg/dL) than the GPA group (32.70 mg/dL, p = 0.0021), the MPA group (30 mg/dL, p = 0.0021), and the HC group (28.55 mg/dL, p = 0.0002). The EPGA group also had a higher IgG4/IgG ratio (0.0644) than the GPA group (0.0322, p = 0.13), the MPA group (0.0289, p = 0.0055), and the HC group (0.0212, p < 0.0001). CONCLUSIONS: Our results indicate that Chinese patients with EGPA have increased levels of serum IgG4. Further study is needed to determine the pathogenic role of IgG4 and IgG4 antineutrophil cytoplasmic antibodies in EGPA.

Long-term fertilization affects functional soil organic carbon protection mechanisms in a profile of Chinese loess plateau soil.

Crop productivity and soil health are limited by organic carbon (OC), however, the variations in the mechanisms of SOC preservation in a complete soil profile subjected to long-term fertilization remains unclear. The objective of the study was to examined the content and profile distribution of the distinctive SOC protection mechanisms on a complete profile (0-100 cm) of Eumorthic Anthrosols in Northwest China after 23 years of chemical and manure fertilization. The soil was fractionated by combined physical-chemical and density floatation techniques. Throughout the profile, significant variations were observed among fractions. In the topsoil (0-20 and 20-40 cm), mineral coupling with the fertilization of manure (MNPK) enhanced total SOC content and recorded for 29% of SOC in the 0-20 and 20-40 cm layers. Moreover, MNPK increased the SOC content of the unprotected cPOC fraction by 60.9% and 61.5% in the 0-20 and 20-40 cm layer, while SOC content was low in the subsoil layers (40-60, 60-80 and 80-100 cm, respectively) compared with the control (C). The highest OC under MNPK in physically protected micro-aggregates (µagg) (6.36 and 6.06 g C kg-1), and occluded particulate organic carbon (iPOC) (1.41 and 1.29 g C kg-1) was found in the topsoil layers. The unprotected cPOC fraction was the greatest C accumulating fraction in the topsoil layers, followed by µagg and H-µSilt fractions in the soil profile, implying that these fractions were the most sensitive to the fertilization treatments. Overall, the unprotected, physically protected, and physico-chemically protected fractions were the dominant fractions for the sequestration of carbon across fertilization treatments and soil layers.