Distribution of blood lead and cadmium levels in healthy children aged 0 to 18 years and analysis of related influencing factors in Henan, China: data findings from 2017 to 2022.

BACKGROUND: There is still a lack of data on blood lead levels (BLLs) and blood lead levels (BLLs) in healthy children of all ages from 0 to 18 years in China. This study was performed to analyze the BLLs and BCLs in healthy children aged 0-18 years from 2017 to 2022 in urban and rural areas of Henan Province, Central China, as well as their relationships with socio-demographic variables and certain relevant exposure factors. To provide a basis for evaluating public health policy development and exposure risk management. METHODS: This was an observational study containing data from 17 prefecture-level cities in Henan, China. Blood Pb and Cd levels were determined using a triple quadrupole inductively coupled plasma mass spectrometer equipped with an autosampler. We first calculated the concentrations of Pb and Cd elements in participants of different genders, ages and years, and then created visual graphs depicting the distribution of each element in terms of gender, age and year (2017-2022). The rates between different groups were compared using the Chi-square test or Fisher exact test (if applicable). The means were compared by one-way ANOVA, medians were compared with the Kruskal-Wallis rank-sum test. Generalized linear models (GLM) were performed to estimate the effects of various factors on blood Pb and Cd concentrations in children. RESULTS: We recruited a total of 25,920 children (16,142 boys and 9,778 girls) aged 0.01 to 18.00 years (2.58 (1.00,6.25)). The median of BLLs was 23.48µg/L, around 9.39% of studied children had elevated BLLs. The median of BCLs was 0.66µg/L, around 1.84% of studied children had elevated BCLs. The median blood Pb concentration was higher in boys (23.90µg/L) than in girls (22.75µg/L) (P<0.001). The median blood Pb concentration was highest in the 3-7 years group (24.51µg/L) and the median blood Cd concentration was highest in the 1-3 years group (0.66µg/L) among all age groups. Both BLLs and BCLs were substantially higher in children in 2020-2022 compared to 2017-2019. Rural children had lower BLLs and higher BCLs. The results of the generalized linear model showed that children in households using Oil, coal, pellet or other wood as a fuel for heating, children with higher frequency of exposure to tobacco smoke and beverage intake had significantly increased chances of elevated BLLs and BCLs. CONCLUSIONS: Pb and Cd exposure of children in this area is relatively low, but associated risk factors continue to exist in vulnerable populations. This study is the first big data analysis of Pb and Cd in children in Henan, China, and provides baseline information for future research.

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators

Purpose To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. Methods In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. Results Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043–1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142–2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102–3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084–12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672–28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan–Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. Conclusion To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation (AU)

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators.

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.

Pan-Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer.

Introduction: Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods: In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results: TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion: Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.

Predictors and prognostic stratification for lupus low disease activity state: results from a prospective clinical trial.

OBJECTIVE: To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. METHOD: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. RESULTS: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the three risk groups based on the identified risk factors. CONCLUSION: Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjögren Syndrome: A Randomized Clinical Trial.

Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches. Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People's Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020. Interventions: Patients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up. Main Outcomes and Measures: The primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24. Results: Sixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, -18.33 points; 95% CI, -28.46 to -8.21 points; P = .001; pain: difference, -10.33 points; 95% CI, -19.38 to -1.29 points; P = .03; fatigue: difference, -11.67 points; 95% CI, -20.65 to -2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells. Conclusions and Relevance: In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells. Trial Registration: ClinicalTrials.gov Identifier: NCT02464319.

Death anxiety and its relationship with family function and meaning in life in patients with advanced cancer-A cross-sectional survey in China.

Objective: This study explores the factors influencing death anxiety in patients with advanced cancer, and to investigate the role of family function on death anxiety, and the correlation between meaning in life and death anxiety. Methods: Patients with advanced cancer who were hospitalized in three institutions from November 2020 to May 2021 were recruited in this cross-sectional study. The Chinese version of the Death and Dying Distress Scale, Meaning in Life Scale For Advanced Cancer Patients and Family APGAR Index were used to assess death anxiety, meaning in life and family function. Pain symptoms were evaluated by the Numeric Rating Scale. Karnofsky Performance Status, patients' socio-demographic and clinical variables were also recorded. Statistical analyses were performed using IBM SPSS Statistics for Windows (version 26.0). Multivariate regression analysis was performed to examine the correlations of social-demographic and clinical variables with family function and death anxiety. Results: Three hundred and twenty-eight patients with advanced cancer were included in this study. The results showed that 12.2% of patients experienced moderate to severe death anxiety. Meaning in Life Scale For Advanced Cancer Patients (acceptance of death, controlling one's life), types of institution (oncology department of tertiary hospitals), self-perceived economic burden (extreme), Karnofsky Performance Status score, age, and medical insurance status (self-paid, inter-provincial medical insurance) were identified as associated factors of death anxiety (R 2 â€‹= â€‹0.335, F â€‹= â€‹20.072, P â€‹< â€‹0.001). Patients with good family function scores had significantly low level of death anxiety in univariate analysis (F â€‹= â€‹5.892, P â€‹= â€‹0.003). Multivariate analysis revealed no significant association between family function and death anxiety. Conclusions: Our results demonstrated that the oncology department of a tertiary hospital, extremely high of self-perceived economic burden, self-pay, and inter-provincial medical insurance might be associated with higher death anxiety in patients with advanced cancer. Lower level death anxiety was associated with higher level acceptance of death, a greater sense of life control, better physical performance, and older age. Further confirmation about the association between family function and death anxiety in patients with advanced cancer is warranted in the future.

Prevalence of Congenital Heart Disease in Chinese Children With Different Birth Weights and Its Relationship to the Neonatal Birth Weight.

Objective: This study aimed to examine the prevalence and the related risk factors of congenital heart disease (CHD) in children with different birth weights in China and the relationship between the subtypes of CHD and birth weight (BW). Methods: This study conducted a cross-sectional survey on the data collected in the children's congenital heart disease database (CHDD) established in China. This database contained data from one Grade A, Level III Children's Public Hospital in Zhengzhou, Henan. The study included all the children and their parents in the database from 2014 to 2020 as the study subjects, and the missing data were processed by means of imputation. Diagnoses of CHD were coded using the International Classification of Diseases version 10 (ICD-10), and subtypes were classified by the codes Q20 to Q26. We reported the prevalence of CHD based on birth weight and gestational age and analyzed the related risk factors for children with CHD in different birth weight groups and factors for children of the same birth weight groups between the CHD groups and the non-CHD groups. The generalized linear model was used to assess the association between the subtypes of CHD and BW by establishing three adjusting models, and the data were stratified for further analysis by urban-rural and infant gender. Results: A total of 42,814 children were identified as having CHD among 5,071,799 live children; the overall prevalence of CHD was 8.44 per 1,000 live births during 2014-2020; and the three subtypes with the highest prevalence of CHD were atrial septal defect (ASD) (2.75‰), ventricular septal defect (VSD) (2.57‰), and patent foramen ovale (PFO) (1.12‰). The prevalence of CHD was 18.87‰ in the group with BW <1,500 g, 12.84‰ in the group with BW 1,500-2,500 g, 8.24‰ in the group with BW 2,500-4,000 g, and 4.80‰ in the group with BW ≥4,000 g. The prevalence of CHD was 16.62‰ in the small for gestational age (SGA) group, 6.99‰ in the appropriate for gestational age (AGA) group, and 6.40‰ in the larger for gestational age (LGA) group. Parental factors such as drinking, smoking, viral infections, peri-pregnancy exposure to radioactive substances, low family monthly expenditure, and low Apgar scores at 1 and 5 min were related to the increased risk of CHD in the offspring. Parental supplementation of folic acid and exercise during the peri-pregnancy period could reduce the risk of CHD in the offspring. The results of Model 3 adjusting for confounding variables showed that infants with ASD had a birth weight 461 g lower (95% CI: -1,085, -128), infants with VSD had a birth weight 426 g lower (95% CI: -932, -120), infants with tetralogy of Fallot (TOF) had a birth weight 532 g lower (95% CI: -987, -168), and without classification, infants with CHD had a birth weight 973 g lower (95% CI: -1,502, -204). Conclusion: In very low birth weight (VLBW) and low birth weight (LBW) infants, CHDs are more prevalent than in the general live-born population. Moreover, some peri-pregnancy factors of parents are closely related to the occurrence of CHD in offspring; different types of heart defects can lead to LBW. Therefore, if the fetus is found to have a heart defect during the prenatal examination, the mother should pay more attention to maintaining weight and ensuring that the fetus is within the normal weight range, thereby increasing the postpartum survival rate, reducing complications, and promoting children's health.

Low Dose Interleukin-2 Ameliorates Sjögren's Syndrome in a Murine Model.

Sjögren's syndrome (SS) is a systemic autoimmune disease with no efficient treatment, and it is associated with dysregulated immune cells and impaired interleukin (IL)-2 signaling. IL-2 is critical for the development and maintenance of Treg cells. The use of low dose of IL-2 (LDIL-2) in the treatment of autoimmune diseases is promising, but the efficacy and mechanism in SS therapy are still to be confirmed. This study aims to investigate the therapeutic effect of LDIL-2 on SS in NOD (non-obese diabetic) mice. NOD mice (female, 8 weeks old) were randomly assigned into three groups (n = 8). Low dose of IL-2 (LDIL-2), high dose of IL-2 (HDIL-2), and isometric sterile water (control) were administered subcutaneously daily from week 8 to week 16. LDIL-2 administration significantly recovered the reduction in saliva flow and suppressed lymphocyte inflammation of the submandibular glands (SMGs) when compared with those treated with sterile water as controls (p < 0.05). SS related biomarkers including ANA, Anti-SSA/Ro, and Anti-SSB/La also declined (p < 0.05). In the low dose of IL-2 treated group, the proportion of CD4+CD25+Foxp3+Tregs in both spleen and cervical-lymph-node were higher than control mice (p < 0.05). Furthermore, CD4+Bcl-6+PD-1+CXCR5+Tfh cells, CD4+IFN-γ+Th1 cells, and CD4+IL-17A+Th17 cells were significantly reduced in LDIL-2 group (p < 0.05). Analysis of the SMGs biopsies showed significantly decreased inflammation scores after LDIL-2 administration and an increase of Tregs with immunohistochemical staining. Our findings provide in vivo evidence that LDIL-2 was an effective therapeutic intervention for SS observed in NOD mice and may restore immune balance through the promotion of Treg and suppression of germinal center (GC) B cells and effector T cells.

Overexpression of galectin2 (LGALS2) predicts a better prognosis in human breast cancer.

BACKGROUND: Galectins (LGALS) are a family of carbohydrate-binding proteins, and LGALS family members have shown prognostic roles in various types of cancers. However, the prognostic significance of some LGALS family members has not been studied in breast malignancy. METHODS: The prognostic value of LGALS family mRNA expression in breast cancer patients was investigated according to distinct clinicopathological features (including lymph node, intrinsic subtype, pathological grade, HER2, and TP53 status) using the Kaplan-Meier plotter database. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression of LGALS in breast cancer and normal breast cells. The aberrant expression of specific LGALS and its correlation with breast cancer outcomes remains elusive. In the present analysis, we comprehensively explored an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer, and cell lines from the widely available Human Protein Atlas (HPA) database. Immunohistochemistry was applied to evaluate the expression of LGALS between cancer and normal tissues. RESULTS: Our results showed that overexpression of LGALS2 mRNA were correlated with satisfactory overall survival among all breast cancer patients. Furthermore, LGALS2 and LGALS4 expression correlated with a better overall survival (OS) in grade III breast cancer patients; LGALS2 also predicted a better OS in basal-like subtype patients, luminal B patients, HER2-overexpressing patients, TP53 mutated and wild breast cancer patients. Notably, the mRNA and protein expression levels of LGALS2 were decreased in cancer cells compared with normal cells (P<0.05). Furthermore, LGALS2 expression in immunostaining score was lower in cancer tissues than in normal tissues (P<0.005). CONCLUSION: In conclusion, LGALS2 has potential as a valuable biomarker for envisaging a satisfactory prognosis in patients with breast tumours, particularly those with luminal and basal B types, all stages and grade III tumours.

Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis.

The imbalance between pathogenic and beneficial species of the intestinal microbiome and metabolism in rheumatoid arthritis (RA) remains unclarified. Here, using shotgun-based metagenome sequencing for a treatment-naïve patient cohort and a "quasi-paired cohort" method, we observed a deficiency of butyrate-producing species and an overwhelming number of butyrate consumers in RA patients. These outcomes mainly occurred in patients with positive ACPA, with a mean AUC of 0.94. This panel was also validated in established RA with an AUC of 0.986 in those with joint deformity. In addition, we showed that butyrate promoted Tregs, while suppressing Tconvs and osteoclasts, due to potentiation of the reduction in HDAC expression and down-regulation of proinflammatory cytokine genes. Dietary butyrate supplementation conferred anti-inflammatory benefits in a mouse model by rebalancing TFH cells and Tregs, as well as reducing antibody production. These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.

Comparison of the deep immune profiling of B cell subsets between healthy adults and Sjögren's syndrome.

OBJECTIVES: Detailed analysis targeting B cell subgroups was considered crucial in monitoring autoimmune diseases and treatment responses. Thus, precisely describing the phenotypes of B cell differentiation and their variation in primary Sjögren's syndrome (pSS) is particularly needed. METHODS: To characterize the proportions and absolute counts of B cell subsets, peripheral blood from 114 healthy adults of China (age range: 19-73 years) and 55 patients with pSS were performed by flow cytometry and CD19, CD20, CD24, CD27, CD38 and IgD were used as surface markers to identify B cell mature process. Age- and gender-stratified analyses were then carried out to improve the interpretation of B cell subsets. RESULTS: The assessments from healthy adults showed that the proportion of naive B cells presented a significant increase with age. A reversal trend was noted that the percentage of B10 decreased markedly with age. In addition, analysis based on gender showed that the relative percentage and number of naive B cells were higher in females than in males whereas the proportions of switched memory B cells and B10 cells were decreased in female. Patients with pSS exhibited a significant expansion in naïve B cells and unswitched memory B cells, accompanied with decreased switched memory B cells and B10 cells, which were identified to be associated with autoantibody production. CONCLUSIONS: Our study presented a reliable analysis by flow cytometry to cover the principal B cell subtypes. These different stages of B lymphocytes may have implications for evaluating the activation of pSS and other autoimmune diseases and treatment efficacy.KEY MESSAGESB cell subsets play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS) and other autoimmune diseases. A practical and accurate flow cytometry method to profile B cell phenotypes in peripheral blood of healthy adults is especially essential.Additionally, we presented reliable reference ranges for B cell subsets in regards to the local population. Age- and gender-related analyses are available to better understand their influence in immune status and treatment outcome.The distribution of B-cell subsets is found substantially altered in patients with pSS, bringing novel avenues for pSS research in the future.

Salivary gland ultrasonography in primary Sjögren's syndrome from diagnosis to clinical stratification: a multicentre study.

BACKGROUND: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren's syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. METHODS: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. RESULTS: The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. CONCLUSIONS: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.

Sonoelastography of salivary glands for diagnosis and clinical evaluation in primary Sjögren's syndrome.

OBJECTIVES: To explore the performance of sonoelastography (SE) in diagnosis and clinical evaluation of primary Sjögren's syndrome (pSS). METHODS: SE examination of major salivary glands was conducted for 79 pSS patients, 39 disease controls and 15 healthy subjects. Elastographic images were determined with a qualitative 4-point scoring method. Receiver operating characteristic (ROC) curve was employed to evaluate the performance of the elasticity scoring method and the best cut-off value was determined. The associations between elasticity scores and disease characteristics were analysed to evaluate the clinical value of SE for pSS. RESULTS: Elasticity scores of parotid and submandibular glands in pSS group were significantly higher than those in the non-pSS group (p<0.001). The sum of the scores of all four glands provided the largest AUC-ROC (0.916, 95% CI 0.87-0.962), compared with that of bilateral parotid glands (0.857, 95% CI 0.794-0.919) and that of bilateral submandibular glands (0.783, 95% CI 0.704-0.863). The optimal cut-off value was 9 for combined evaluation of all four glands (81% sensitivity and 87% specificity, respectively). The elasticity scores of parotid glands in patients with disease duration >10 years experienced significant difference as compared to patients with disease duration ≤5 years and 5-10 years respectively (p=0.007, 0.009, respectively), whereas it presented no variations between the disease duration ≤5 years and 5-10 years (p=0.952). CONCLUSIONS: Sonoelastography, performed simultaneously with ultrasonography, is an additional tool for the assessment of the salivary glands in patients with pSS. The elasticity is closely associated with disease duration.

Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis.

The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells (BMSCs) in the tumor microenvironment (TME) facilitates the survival and therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression in primary tumor tissues or bone marrow (BM) metastases was closely associated with the disease risk and prognosis of NB patients. IL6 secretion from immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, LPC), an ortho-naphthoquinone natural product, significantly prevented the iBMSC-induced malignant transformation effect on NB cells through suppressing the expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and provide theoretical basis for the clinical application of LPC as a potential IL6 inhibitor in high-risk refractory NB patients.

When Different Language Groups Meet Online: Covert and Overt Focus on Form in Text-Based Chats.

Focus on form has been extensively studied in text-based online dyadic chats but much less has been explored in group chats with interlocutors from different language backgrounds. Additionally, there are very few studies investigating covert focus on form. This study investigated the effects of interlocutor types on errors and focus on form episodes, both covert and overt, in text-based online group chats. We collected chat logs from two collaborative online international learning projects. One project was developed for the collaboration between an English course at a Chinese university and an art history course at a U.S. university; the other between another cohort of the same English course and a cultural studies course at a Mexican university. We compared errors, feedback, and other characteristics of focus on form episodes between the two projects. Analyses revealed significant differences in characteristics such as overtness (overt, covert), linguistic focus (mechanical, lexical, and grammatical), and source (code, message). However, no significant differences were found for the type of focus on form (preemptive, reactive), presence of uptake, uptake quality (successful, unsuccessful), and repair provider (self, other). Students showed a preference for self-repair over other-repair and for lexical focus over mechanical and grammatical foci in both projects. Overall, only a small proportion of errors were followed by feedback. Therefore, a small amount of uptake and successful uptake occurred in both projects. The results can shed light on how instructors could provide effective scaffolding and tasks to make virtual exchange projects more rewarding.