RMVar 2.0: an updated database of functional variants in RNA modifications.

Evaluating the impact of genetic variants on RNA modifications (RMs) is crucial for identifying disease-associated variants and understanding the pathogenic mechanisms underlying human diseases. Previously, we developed a database called RMVar to catalog variants linked to RNA modifications in humans and mice. Here, we present an updated version RMVar 2.0 (http://rmvar.renlab.cn). In this updated version, we applied an enhanced analytical pipeline to the latest RNA modification datasets and genetic variant information to identify RM-associated variants. A notable advancement in RMVar 2.0 is our incorporation of allele-specific RNA modification analysis to identify RM-associated variants, a novel approach not utilized in RMVar 1.0 or other comparable databases. Furthermore, the database offers comprehensive annotations for various molecular events, including RNA-binding protein (RBP) interactions, RNA-RNA interactions, splicing events, and circular RNAs (circRNAs), which facilitate investigations into how RM-associated variants influence post-transcriptional regulation. Additionally, we provide disease-related information sourced from ClinVar and GWAS to help researchers explore the connections between RNA modifications and various diseases. We believe that RMVar 2.0 will significantly enhance our understanding of the functional implications of genetic variants affecting RNA modifications within the context of human disease research.

Id1 expression in CD4 T cells promotes differentiation and function of follicular helper T cells and upregulation of related functional molecules.

Although the roles of E proteins and inhibitors of DNA-binding (Id) in T follicular helper (TFH) and T follicular regulatory (TFR) cells have been previously reported, direct models demonstrating the impact of multiple E protein members have been lacking. To suppress all E proteins including E2A, HEB and E2-2, we overexpressed Id1 in CD4 cells using a CD4-Id1 mouse model, to observe any changes in TFH and TFR cell differentiation. Our objective was to gain better understanding of the roles that E proteins and Id molecules play in the differentiation of TFH and TFR cells. The CD4-Id1 transgenic (TG) mice that we constructed overexpressed Id1 in CD4 cells, inhibiting E protein function. Our results showed an increase in the proportion and absolute numbers of Treg, TFH and TFR cells in the spleen of TG mice. Additionally, the expression of surface characterisation molecules PD-1 and ICOS was significantly upregulated in TFH and TFR cells. The study also revealed a downregulation of the marginal zone B cell precursor and an increase in the activation and secretion of IgG1 in spleen B cells. Furthermore, the peripheral TFH cells of TG mice enhanced the function of assisting B cells. RNA sequencing results indicated that a variety of TFH-related functional molecules were upregulated in TFH cells of Id1 TG mice. In conclusion, E proteins play a crucial role in regulating TFH/TFR cell differentiation and function and suppressing E protein activity promotes germinal centre humoral immunity, which has important implications for immune regulation and treating related diseases.

Expression of GPR56 reflects a hypoactivated state of circulating B cells and is downregulated in B cell subsets in patients with early-stage lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD.

Differential GPR56 Expression in T Cell Subpopulations for Early-Stage Lung Adenocarcinoma Patient Identification.

OBJECTIVE: This study aimed to investigate the expression of GPR56 in the T cells of early-stage lung adenocarcinoma (LUAD) patients and clarify its diagnostic significance. METHODS: Blood samples were collected from 32 patients with stage IA LUAD and 31 healthy controls. GPR56 and perforin were analysed in circulating T-cell subsets by flow cytometry. In addition, a correlation between perforin and GPR56 expression was detected. Changes in GPR56+ cells in early LUAD patients were analysed, and the diagnostic significance of GPR56+ T cells for early LUAD was studied by receiver operating characteristic (ROC) curve analysis. RESULTS: The expression of GPR56 in CD8+ T cells from early-stage LUAD patients was significantly greater than that in CD4+ T cells. The percentage of perforin-positive GPR56+ cells in early-stage LUAD patients was high. GPR56 levels in the T cells of LUAD patients were significantly lower than those in healthy controls. ROC analysis revealed that the area under the curve for the percentage of GPR56-positive CD8+ TEMRA cells to distinguish early-stage LUAD patients from healthy individuals- reached 0.7978. CONCLUSION: The decreased expression of GPR56 in the peripheral blood of early-stage LUAD patients correlated with perforin levels, reflecting compromised antitumor immunity and aiding early-stage LUAD screening.

The altered HLA-DQ expression in peripheral blood T cells of chronic hepatitis B patients characterizes the function of T cells.

OBJECTIVE: This study aimed to clarify the expression of HLA-DQ and granulysin in peripheral blood T-cell subsets in patients with chronic hepatitis B virus (CHB) and to evaluate their significance in assisting CHB diagnosis and immune status assessment. METHODS: Peripheral blood from 34 CHB patients, 36 inactive HBsAg carriers and 33 healthy controls were collected, and HLA-DQ and granulysin in a series of T-cell subsets were analysed by flow cytometry. The ability to secrete IL-10 and IFN-γ and the functional T-cell subsets were measured in Treg and CD4 cells expressing HLA-DQ or not. Correlation analyses were further conducted between HLA-DQ/granulysin-related subsets and clinical indicators of HBV infection, and ROC curves were built to evaluate diagnosis efficiency of HLA-DQ-related subsets. RESULTS: HLA-DQ+ percentages in circulating CD4 T cells were downregulated in CHB patients. The proportions of HLA-DQ + Tfh in CHB were upregulated while HLA-DQ+ percentages in Treg were decreased. In terms of function, the IFN-γ secretion ability of CD4 + T cells and IL-10 secretion in Tregs were stronger in HLA-DQ+ than HLA-DQ- subsets. HLA-DQ + CD4 + T cells and HLA-DQ + Treg were negatively correlated with HBV-DNA, while HLA-DQ + Tfh and Tfc cells were positively correlated with HBV-DNA and ALT. HLA-DQ + Treg/Tfh/Tfc could help to distinguish CHB from inactive HBsAg carriers. CONCLUSION: HLA-DQ on T cells can characterize the function of T-cell subsets and analysis of HLA-DQ can help to evaluate immune status and assist in diagnosis of CHB.

Changes in circulating TCF1- and GARP-associated regulatory T cell subsets reflect the clinical status of patients with chronic HBV infection.

This study aimed to clarify the expression changes and clinical significance of regulatory T (Treg) cells and follicular regulatory T (TFR) cell subsets divided by glycoprotein A repetitions predominant protein (GARP) and T cell factor 1(TCF1) in peripheral blood of patients with chronic HBV infection. The peripheral blood of 26 chronic hepatitis B (CHB) patients, 27 inactive HBsAg carriers and 32 healthy controls were collected and GARP + percentages in Treg and TFR cells were analyzed by flow cytometry. In addition, Treg and TFR cell subsets sorted by CD62L and TCF1 were analyzed and compared. Correlation analyses were performed between Treg and TFR cell subpopulations and clinical parameters as well as cytokine concentrations, including IL-21, IL-10 and TGF-ß1 in plasma. Circulating Treg and TFR levels were elevated in CHB patients. Moreover, GARP and TCF1 were up-regulated in circulating Treg and TFR cells of CHB patients. TCF1 + CD62L- Treg cells were increased while TCF1-CD62L + Treg cells were decreased in CHB patients. TCF1 + CD62L- and TCF1-CD62L- TFR cells were increased while TCF1 + CD62L + TFR cells were decreased in CHB patients. TCF1 + CD62L- Treg cells were positively correlated with HBV DNA, ALT and plasma IL-10, while TCF1 + CD62L + TFR cells were negatively correlated with HBV DNA, HBeAg, HBsAg, ALT, AST, T-BIL and positively correlated with plasma IL-21. Treg and TFR subsets sorted by TCF1, CD62L and GARP were changed in CHB patients. Changes in Treg and TFR functional subsets are associated with antiviral immunity in CHB patients.

Cytotoxic T Lymphocytes Expressing GPR56 are Up-regulated in the Peripheral Blood of Patients with Active Rheumatoid Arthritis and Reflect Disease Progression.

OBJECTIVE: This study aims to elucidate the changes in the percentage of GPR56 and/or granzyme B (GZMB) positive cells in rheumatoid arthritis (RA) CD4 and CD8 T lymphocytes, and to explore their clinical value in diagnosing and reflecting the progression of RA. METHODS: The percentages of GPR56 and/or GZMB positive cells were analyzed in peripheral blood (PB) and spleen T cells in a collagen-induced arthritis (CIA) model established in DBA/1 mice. The percentages of GPR56+ and/or GZMB+ cells were further analyzed in PBs from RA patients and healthy controls. Correlation analysis was performed between clinical indicators and GPR56+, GZMB+, and GPR56+ GZMB+ T cells. Receiver operating characteristic (ROC) curves were used to evaluate the value of GPR56 and GZMB in differentiating active and stable remitting RA. RESULTS: GPR56+ levels were increased in CD4 and CD8 T cells in the PB of CIA mice. The percentages of GPR56+ and GZMB+ cells were increased in both CD4 and CD8 T cell subsets in patients with active RA. GPR56+, GZMB+, and GPR56+ GZMB+ cells were positively correlated with rheumatoid factor and DAS28. ROC analysis revealed that AUCs for GPR56+, GZMB+, and GPR56+ GZMB+ cell percentages to distinguish active RA from stable remission RA were 0.7106, 0.6941, 0.7024, with cut-off values of 16.35, 16.40, 14.80 in CD4 + T cells, and 0.8031, 0.8086, 0.8196 with cut-off values 60.25, 62.15, 40.15 in CD8 + T cells, respectively. CONCLUSIONS: GPR56+ and/or GZMB+ T cells are up-regulated in patients with active RA and reflect their condition. The detection of GPR56 and GZMB is helpful for RA disease assessment.

Additional cognitive behavior therapy for persistent postural-perceptual dizziness: a meta-analysis.

OBJECTIVE: To investigate whether additional Cognitive Behavior Therapy (CBT) combined with conventional therapy improves outcomes for patients with Persistent Postural-Perceptual Dizziness (PPPD) compared with conventional therapy alone. METHODS: Two reviewers independently searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant Randomized Controlled Trials (RCTs) examining CBT for PPPD which were conducted and published in English from January 2002 to November 2022. RCTs reporting any indicators for assessing corresponding symptoms of PPPD were included, such as Dizziness Handicap Inventory (DHI), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Two independent reviewers conducted extraction of relevant information and evaluation of risk of bias. The Cochrane Collaboration risk of bias tool version 1.0 was used to evaluate risks and assess the quality of the included studies, and Cochrane Review Manager 5.3 software (RevMan 5.3) was used to perform meta-analyses. RESULTS: The results of six RCTs indicated that combining additional CBT with conventional therapy significantly improved outcomes for PPPD patients compared with conventional therapy alone, especially in DHI-Total scores (Mean Difference [MD = -8.17], 95% Confidence Interval [95% CI: -10.26, -6.09], p < 0.00001), HAMA scores (MD = -2.76, 95% CI: [-3.57, -1.94], p < 0.00001), GAD-7 scores (MD = -2.50, 95% CI [-3.29, -1.70], p < 0.00001), and PHQ-9 scores (MD = -2.29, 95% CI [-3.04, -1.55], p < 0.00001). Subgroup analysis revealed a significant benefit of additional CBT compared with conventional therapies alone, including Vestibular Rehabilitation Therapy (VRT) (MD = -8.70, 95% CI: [-12.17, -5.22], p < 0.00001), Selective Serotonin Reuptake Inhibitor (SSRI) (with controlled SSRI: MD = -10.70, 95% CI: [-14.97, -6.43], p < 0.00001), and VRT combined with SSRI (MD = -6.08, 95% CI [-9.49, -2.67], p = 0.0005) in DHI-Total scores. CONCLUSION: Additional CBT combined with conventional therapy may provide additional improvement for patients with PPPD compared with conventional therapy alone. However, more RCTs are needed to support and guide the application of CBT in treating PPPD. LEVEL OF EVIDENCE: I; Systematic review of RCTs.

Helios characterized circulating follicular helper T cells with enhanced functional phenotypes and was increased in patients with systemic lupus erythematosus.

Helios was related to the immunosuppressive capacity and stability of regulatory T cells. However, the significance of Helios in follicular help T (TFH) and follicular regulatory T (TFR) cells is unclear. This research aimed to clarify the significance of Helios (IKZF2) in TFH and TFR cells and its clinical value in systemic lupus erythematosus (SLE). IKZF2 mRNA in different cell subsets was analyzed. Helios+ percentages in TFH and TFR cells were identified in the peripheral blood of 75 SLE patients and 62 HCs (healthy controls). PD-1 and ICOS expression were compared between Helios+ and Helios- cells. The capacity of TFH cells to secrete IL-21 and TFR cells to secrete IL-10 was measured. Correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted to assess the clinical significance of Helios-related TFH and TFR cell subsets in SLE. There was Helios expression in TFH and TFR cells. PD-1 and ICOS were lower in Helios+ TFR than in Helios- TFR. ICOS was increased in Helios+ TFH cells compared with Helios- TFH cells, and ICOS in Helios+ TFH cells was downregulated in SLE. Helios+ TFH cells secreted more IL-21 than Helios- TFH cells, and Helios+ TFH cells from SLE patients had a stronger IL-21 secretion than HCs. Helios+ TFH percentages were negatively correlated with C3 and C4 and positively related to CRP and SLEDAI, and the AUC of Helios+ TFH to distinguish SLE from HC was 0.7959. Helios characterizes circulating TFH cells with enhanced function. Increased Helios+ TFH cells could reflect the autoimmune status of SLE.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer.

OBJECTIVE: This study aimed to investigate the changes of follicular helper T (TFH) and follicular regulatory T (TFR) cell subpopulations in patients with non-small cell lung cancer (NSCLC) and their significance. METHODS: Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls. Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1 (PD-1) and inducible co-stimulator (ICOS), and TFR cell subpopulation based on cluster determinant 45RA (CD45RA) and forkhead box protein P3 (FoxP3). The levels of interleukin-10 (IL-10), interleukin-17a (IL-17a), interleukin-21 (IL-21), and transforming growth factor-ß (TGF-ß) in the plasma were measured, and changes in circulating B cell subsets and plasma IgG levels were also analyzed. The correlation between serum cytokeratin fragment antigen 21-1 (CYFRA 21-1) levels and TFH, TFR, or B cell subpopulations was further explored. RESULTS: The TFR/TFH ratio increased significantly in NSCLC patients. The CD45RA+FoxP3int TFR subsets were increased, with their proportions increasing in stages II to III and decreasing in stage IV. PD-1+ICOS+TFH cells showed a downward trend with increasing stages. Plasma IL-21 and TGF-ß concentrations were increased in NSCLC patients compared with healthy controls. Plasmablasts, plasma IgG levels, and CD45RA+FoxP3int TFR cells showed similar trends. TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages I-III and negatively correlated with CYFRA 21-1 in stage IV. CONCLUSION: Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC, which is associated with serum CYFRA 21-1 levels and reflects disease progression.

SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients.

This study aims to elucidate the expression and functionality of SIT1 in circulating CD8/CD4 + T cells in humans and to delineate its significance in systemic lupus erythematosus (SLE) patients. We employed multiparametric flow cytometry to investigate the expression of SIT1 in circulating CD8/CD4 + T cells and their respective subsets, comparing healthy controls (HCs) with SLE patients. Furthermore, we assessed the levels of granzyme B, perforin, IL-17, and IFN-γ in SIT1-related CD8/CD4 + T cells from both HCs and SLE patients, both before and after PMA stimulation. Clinically, we conducted receiver operating characteristic curve analysis and correlation analysis to evaluate the clinical relevance of SIT1-related CD8/CD4 + T cells in SLE patients. SIT1 exhibited higher expression in CD4 + T cells, with SIT1 - T cells demonstrating elevated levels of granzyme B, perforin, and IFN-γ compared to SIT1 + T cells. PMA-stimulated T cells exhibited reduced SIT1 expression compared to unstimulated T cells. SLE patients displayed increased SIT1 + proportions in CD8 + T cells and decreased SIT1 + CD4 + T cell numbers. Additionally, SIT1 + cells in SLE patients exhibited significantly higher levels of granzyme B and perforin compared to HCs. SIT1 + cells demonstrated significant associations with clinical indicators in SLE patients, with indicators related to SIT1 proving valuable in the diagnosis of SLE patients. SIT1 is inversely correlated with T cell activation. In SLE patients, SIT1 expression is altered in T cells concomitant with an augmented secretion of cytotoxic molecules. This upregulation may contribute to the pathogenesis of SLE and enhance its diagnostic potential.

Vanin-2 is expressed in peripheral blood T cells and upregulated in SLE patients.

Members of the vanin gene family include VNN1, VNN2 and VNN3 in humans. Although the functions of vanins have been widely examined in myeloid cells, their expression and functions have not been clarified in T lymphocytes. This study aimed to elucidate the significance of Vanin-2 (VNN2) on human peripheral blood T lymphocytes and study its expression in systemic lupus erythematosus (SLE). The differential expression of Vanins was analysed by bioinformatics. VNN2 expressions in peripheral blood T cell subsets were analysed by single-cell RNA sequencing data and flow cytometry. Changes of VNN2 expression before and after T cell activation were further clarified by western blot. The function of VNN2+ cells was studied by granzyme B and perforin detection. Changes in VNN2+ proportions in T cell subsets of SLE patients were further analysed. In the present study, only VNN2 among vanins showed distinguishable expression in T cells. VNN2+ percentages were higher in CD8+ T cells than in CD4+ T cells. VNN2+ T cells were with a higher memory T cell composition. VNN2 expression was significantly increased after T cell stimulation. VNN2+ T cells had higher levels of granzyme B and perforin secretion than VNN2- T cells. Clinically, VNN2+ percentages in T cells of SLE patients were upregulated. Together, these data suggested that VNN2 is expressed in peripheral blood T cells characterized more granzyme B and perforin secretion, and increased VNN2+ T cells in SLE patients could reflect altered T cell functions in vivo.

TSCRE: a comprehensive database for tumor-specific cis-regulatory elements.

Cis-regulatory elements (CREs) and super cis-regulatory elements (SCREs) are non-coding DNA regions which influence the transcription of nearby genes and play critical roles in development. Dysregulated CRE and SCRE activities have been reported to alter the expression of oncogenes and tumor suppressors, thereby regulating cancer hallmarks. To address the strong need for a comprehensive catalogue of dysregulated CREs and SCREs in human cancers, we present TSCRE (http://tscre.zsqylab.com/), an open resource providing tumor-specific and cell type-specific CREs and SCREs derived from the re-analysis of publicly available histone modification profiles. Currently, TSCRE contains 1 864 941 dysregulated CREs and 68 253 dysregulated SCREs identified from 1366 human patient samples spanning 17 different cancer types and 9 histone marks. Over 95% of these elements have been validated in public resources. TSCRE offers comprehensive annotations for each element, including associated genes, expression patterns, clinical prognosis, somatic mutations, transcript factor binding sites, cancer-type specificity, and drug response. Additionally, TSCRE integrates pathway and transcript factor enrichment analyses for each study, enabling in-depth functional and mechanistic investigations. Furthermore, TSCRE provides an interactive interface for users to explore any CRE and SCRE of interest. We believe TSCRE will be a highly valuable platform for the community to discover candidate cancer biomarkers.

BioTreasury: a community-based repository enabling indexing and rating of bioinformatics tools.

The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments. Therefore, to aid scientists in making informed choices, a community-based platform that indexes and rates bioinformatics tools is urgently needed. In this study, we introduce BioTreasury ( http://biotreasury.rjmart.cn ), an integrated community-based repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics tools. BioTreasury offers a comprehensive collection of well-indexed bioinformatics software, tools, and databases, totaling over 10,000 entries. In the past two years, we have continuously improved and maintained BioTreasury, adding several exciting features, including creating structured homepages for every tool and user, a hierarchical category of bioinformatics tools and classifying tools using large language model (LLM). BioTreasury streamlines the tool submission process with intelligent auto-completion. Additionally, BioTreasury provides a wide range of social features, for example, enabling users to participate in interactive discussions, rate tools, build and share tool collections for the public. We believe BioTreasury can be a valuable resource and knowledge-sharing platform for the biomedical community. It empowers researchers to effectively discover and evaluate bioinformatics tools, fostering collaboration and advancing bioinformatics research.

Alterations in Helios+ T cell subsets in peripheral blood of early-stage lung adenocarcinoma patients: Implications for early diagnosis.

OBJECTIVE: This study aimed to investigate the changes and significance of circulating Helios-associated T cell subsets in patients with early-stage lung adenocarcinoma (LUAD). METHODS: Blood samples were collected from 35 healthy controls and 34 patients with early-stage LUAD. Flow cytometry was used to analyze various CD4+ T cell subsets, including regulatory T(Treg) cells, follicular regulatory T(Tfr) cells, follicular helper T (Tfh) cells, and conventional T (con-T) cells. Correlation analysis was conducted to investigate the association of Helios-related subsets with clinical indicators. The ROC curve was used to explore the potential clinical value of Helios+ T cell subsets in the screening of patients with early LUAD. Fifteen of these patients were tracked after lung cancer resection and changes in Helios+ T cell subsets before and after treatment were analyzed. RESULTS: The percentage and absolute number of Tregs were up-regulated in LUAD patients while Tfh and con-T cells expressing Helios were down-regulated. Absolute counts of Tfr and con-T cells and Helios expression in Tfr and Treg decreased significantly after resection. Helios+ Tfh and con-T were negatively correlated with certain tumor markers. Areas under the curve (AUCs) of percentages and absolute counts of Helios+ Tfh, Treg, Tfr and con-T cells to distinguish early LUAD from healthy individuals were 0.7277, 0.5697, 0.5718, 0.7210 (percentages), 0.7336, 0.7378, 0.5908 and 0.7445(absolute numbers), respectively. CONCLUSION: Helios+ T cell subsets in peripheral blood of early-stage LUAD patients has changed significantly, which may be related to the pathogenesis of LUAD and could help for early diagnosis of LUAD.

Changes in the expression of T-cell factor-1 in follicular helper T cells reflect the condition of systemic lupus erythematosus patients.

OBJECTIVE: This study aimed to identify changes in T-cell factor-1 (TCF1) in circulating T-cell subsets of systemic lupus erythematosus (SLE) patients and to explore their significance in SLE. METHODS: Peripheral blood was collected from 41 SLE patients and 45 healthy controls (HCs). TCF1 in follicular helper T (TFH), follicular regulatory T (TFR) and regulatory T (Treg) cells was analyzed by flow cytometry. Interleukin-21 (IL-21), programmed death receptor 1 (PD-1) and killer cell lectin-like receptor G1 (KLRG1) were detected and compared among TFH subsets sorted according to TCF1 and CD62L expression. Correlation analyses were conducted between TCF1-related TFH cell subsets and autoantibody levels, systemic lupus erythematosus disease activity index (SLEDAI), and plasmablast levels of SLE patients. RESULTS: Absolute numbers of TCF1- TFH and TCF1+ Treg cells were increased in SLE patients. According to TCF1 and CD62L expression, circulating TFH cells and Tregs were sorted into four subsets. CD62L+TCF1+ TFH cell percentages were decreased, and CD62L-TCF1- TFH cells were increased. CD62L+TCF1+ Treg cell percentages were increased, and CD62L-TCF1- Treg cell percentages were decreased. KLRG1+ percentages in CD62L-TCF1-TFH were higher in SLE patients than in HCs. Functionally, CD62L+TCF1+ TFH cells had stronger IL-21 secretion, while CD62L-TCF1-TFH cells had weaker IL-21 secretion and lower PD-1 expression. TCF1- and CD62L-TCF1- TFH numbers were positively correlated with anti-ribosomal P, anti-dsDNA and SLEDAI. CONCLUSION: The increased TFH cells in SLE patients were mostly TCF1-negative subsets with weakened function. Changes in TCF1-related subsets can reflect the condition and abnormal humoral immunity of SLE patients.

Inflammatory Cytokine-Neutralizing Antibody Treatment Prevented Increases in Follicular Helper T Cells and Follicular Regulatory T Cells in a Mouse Model of Arthritis.

Background: Follicular T helper (TFH) and follicular regulatory T (TFR) cells play important roles in humoral immunity. Nevertheless, their significance in rheumatoid arthritis (RA) pathogenesis has not been fully elucidated. As an important treatment strategy, the effect of inflammatory factor-neutralizing antibodies on TFH and TFR in RA remains unclear. Methods: We used the collagen-induced arthritis (CIA) mouse model to illustrate the quantity and functional changes in TFH and TFR cells. The changes of plasmablast, TFH and TFR cells in the spleen and peripheral blood of CIA mice were analyzed by flow cytometry. The levels of TFH and TFR and their functional subsets in the spleen after anti-inflammatory antibody treatment were analyzed and compared. The functional changes of TFH and TFR in CIA mice before and after treatment were detected by in vitro culture experiments. Results: Plasmablast levels were increased in CIA spleen and peripheral blood and both TFH and TFR cell levels were upregulated. TFH and TFR cells were decreased significantly after the anti-inflammatory antibody treatment. TIGIT+ and TIGIT+CD226- TFH cells in CIA mouse spleen were elevated and PD-1 and ICOS expression on spleen TFH and TFR cells was increased. Both the ability of TFH cells to secrete IL-21 and aid B cells and the ability of TFR cells to secrete IL-10 and inhibit TFH cells were enhanced in the CIA mice. After antibody treatment, the cell subsets and functions were recovered. Conclusion: Germinal center TFH and TFR cells were increased and their functions were enhanced. With inflammatory factor-neutralizing antibody treatment, TFH and TFR subsets and their functions returned to normal. These findings provide important information on the dynamics of humoral immune-related cell subsets in RA and the effects of treatment on them.

Additional cognitive behavior therapy for persistent postural-perceptual dizziness: a meta-analysis

Abstract Objective To investigate whether additional Cognitive Behavior Therapy (CBT) combined with conventional therapy improves outcomes for patients with Persistent Postural-Perceptual Dizziness (PPPD) compared with conventional therapy alone. Methods Two reviewers independently searched PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant Randomized Controlled Trials (RCTs) examining CBT for PPPD which were conducted and published in English from January 2002 to November 2022. RCTs reporting any indicators for assessing corresponding symptoms of PPPD were included, such as Dizziness Handicap Inventory (DHI), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Two independent reviewers conducted extraction of relevant information and evaluation of risk of bias. The Cochrane Collaboration risk of bias tool version 1.0 was used to evaluate risks and assess the quality of the included studies, and Cochrane Review Manager 5.3 software (RevMan 5.3) was used to perform meta-analyses. Results The results of six RCTs indicated that combining additional CBT with conventional therapy significantly improved outcomes for PPPD patients compared with conventional therapy alone, especially in DHI-Total scores (Mean Difference [MD = −8.17], 95% Confidence Interval [95% CI: −10.26, −6.09], p< 0.00001), HAMA scores (MD = −2.76, 95% CI: [−3.57, −1.94], p< 0.00001), GAD-7 scores (MD = −2.50, 95% CI [−3.29, −1.70], p< 0.00001), and PHQ-9 scores (MD = −2.29, 95% CI [−3.04, −1.55], p< 0.00001). Subgroup analysis revealed a significant benefit of additional CBT compared with conventional therapies alone, including Vestibular Rehabilitation Therapy (VRT) (MD = −8.70, 95% CI: [−12.17, −5.22], p< 0.00001), Selective Serotonin Reuptake Inhibitor (SSRI) (with controlled SSRI: MD = −10.70, 95% CI: [−14.97, −6.43], p< 0.00001), and VRT combined with SSRI (MD = −6.08, 95% CI [−9.49, −2.67], p= 0.0005) in DHI-Total scores. Conclusion Additional CBT combined with conventional therapy may provide additional improvement for patients with PPPD compared with conventional therapy alone. However, more RCTs are needed to support and guide the application of CBT in treating PPPD. Level of evidence: I; Systematic review of RCTs.