Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

Increase in Mitochondrial Mass of Lymphocyte Subsets in Anti-MDA5 and TIF1-γ-Positive Dermatomyositis Patients.

OBJECTIVES: The mitochondrial function in anti-MDA5 and TIF1-γ-positive dermatomyositis (DM) is relatively unknown. This study attempted to explore mitochondrial mass within the peripheral lymphocyte subsets of anti-MDA5 and TIF1-γ-positive DM. METHODS: This cross-sectional study enrolled 109 DM patients and 32 healthy controls (HCs). The mitochondrial mass of peripheral lymphocyte subsets was analyzed via flow cytometry using median fluorescence intensity assessment. RESULTS: Compared with HCs, there was an abnormal change in peripheral lymphocyte subsets in anti-MDA5 and anti-TIF1-γ-positive DM patients. Anti-MDA5 and anti-TIF1-γ-positive DM patients also exhibited a significantly elevated mitochondrial mass in peripheral lymphocyte subsets. Furthermore, anti-MDA5 antibody levels were positively associated with the mitochondrial mass of most lymphocyte subsets in anti-MDA5-positive DM patients. Univariate logistic regression analysis indicated that the increased mitochondrial mass in some peripheral lymphocyte subsets was related to the occurrence of anti-MDA5-positive DM and presence of anti-MDA5 antibodies. Similar results were obtained in anti-TIF1-γ-positive DM patients. CONCLUSIONS: Abnormal lymphocyte subset counts and percentages as well as altered mitochondrial mass in anti-MDA5 and TIF1-γ-positive DM patients were associated with anti-MDA5 and TIF1-γ antibodies. We believe that these results may provide novel mitochondria-based insights into DM pathogenesis.

Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China.

OBJECTIVE: The current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred. METHOD: A cross-sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared. RESULT: Patients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO. CONCLUSION: This present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.

Human Autoantigen Atlas: Searching for the Hallmarks of Autoantigens.

Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.

Infectious agents and pathogenesis of Behçet's disease: An extensive review.

Behçet's disease (BD) is a multisystemic chronic vasculitis. Sustained and enhanced immune responses were reportedly associated with active BD. Although genetic polymorphisms increase development risk, genetic factors alone cannot account for BD development, suggesting the involvement of exogenous factors. Also, how various infectious agents promote BD in high-risk populations is not fully understood. In this review, we summarized the current findings on the associations of infectious agents with BD pathogenesis. The review also highlights the potential microbial risk factors and their pathogenic role in BD progression. Interactions between genetic and infectious risk factors was also discussed. Furthermore, evidence implied that after the eradication of infectious agents, BD symptoms and recurrence decreased, thus highlighting that combined use of antibiotics may be an effective therapy for BD. Finally, we summarized the main limitation of the current related studies, providing valuable insights and a basis for future studies on BD pathogenic factors.

Myelin basic protein and index for neuro-Behçet's disease.

Neuro-Behçet's disease (NBD) contributes to poor prognosis in BD patients which lacks reliable laboratory biomarkers in assessing intrathecal injury. This study aimed to determine the diagnostic value of myelin basic protein (MBP), an indicator of central nervous system (CNS) myelin damage, in NBD patients and disease controls. Paired samples of cerebrospinal fluid (CSF) and serum MBP were measured using ELISA, while IgG and Alb were routinely examined before the MBP index was developed. CSF and serum MBP in NBD were significantly higher than in NIND, which could distinguish NBD from NIND with a specificity exceeding 90%, moreover, they could also be excellent discriminators for acute NBD and chronic progressive ones. We found positive linkage between MBP index and IgG index. Serial MBP monitoring confirmed serum MBP's sensitive response to disease recurrences and drug effects, whereas MBP index suggests relapses prior to clinical symptoms. MBP has high diagnostic yield for NBD with demyelination and identifies CNS pathogenic processes before imaging or clinical diagnosis.

Progress and challenges in the use of blood biomarkers in relapsing polychondritis.

Relapsing polychondritis (RP) is a rare inflammatory disease with significant individual heterogeneity that involves systemic organs. The diagnosis of RP mainly depends on the clinical manifestations; currently, there are no molecular biomarkers routinely evaluated in clinical practice. Biomarkers have diagnostic or monitoring values and can predict response to treatment or the disease course. Over the years, many biomarkers have been proposed to facilitate diagnosis and prognosis. Unfortunately, ideal biomarkers to diagnose RP have not yet been discovered. Most of the molecular biomarkers in RP are immunological biomarkers, with autoantibodies and proteins related to cartilage damage in the blood being the most common. Alterations in some genes (HLA typing and UBA1 somatic mutation) were detected in patients with RP, which could serve as a potential biomarker for the diagnosis of RP. Moreover, proinflammatory cytokines and lymphocyte levels, and certain laboratory tests, have certain values of RP diagnosis and disease activity assessment but lack specificity and sensitivity. This review describes the different types of biomarkers and their clinical correlation with respect to the diagnosis of RP and disease activity. Research on biomarkers and disease pathology is ongoing to identify the ideal biomarkers that are sensitive and specific for RP.

Negative serum (1,3) -ß-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR.

OBJECTIVE: The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results. METHODS: This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort. RESULTS: Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG. CONCLUSIONS: Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

A unified serum IgG4 cut-off level for the diagnosis of IgG4-related disease using a wide array of kits.

OBJECTIVES: An immunoglobulin G4 (IgG4) level above 1350 mg/L is one of the comprehensive criteria for the diagnosis of IgG4-related disease (IgG4-RD). The purpose of this study was to evaluate the differences in IgG4 levels determined using reagents from two main manufacturers and their concordance with clinical diagnosis. METHODS: IgG4 levels were measured in 309 patients, including 146, 40, 42, 41, and 40 patients with untreated IgG4-RD, pancreatic cancer, primary Sjogren syndrome, systemic lupus erythematosus, and idiopathic retroperitoneal fibrosis, respectively, and 141 healthy controls. The results obtained using the Binding Site and Siemens reagents were compared in patients with IgG4-RD. RESULTS: The serum IgG4 level measured using the Siemens reagent was almost two times that measured using the Binding Site reagent. The rate of IgG4-negative patients, which was 19.9% based on measurement using the Binding Site reagent, was only 4.8% based on measurement using the Siemens reagent (p < .001). CONCLUSIONS: There were significant differences in serum IgG4 levels based on commonly used reagents from different manufacturers. The IgG4 cut-off level of 1350 mg/L was not suitable for all detection reagents. Clinicians and patients should be cognizant of these differences associated with the specific detection reagents when evaluating the test results.

Distinct metabolic biomarkers to distinguish IgG4-related disease from Sjogren's syndrome and pancreatic cancer and predict disease prognosis.

BACKGROUND: The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren's syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases. METHODS: Untargeted liquid chromatography-tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis. RESULTS: The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, D-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8). CONCLUSIONS: Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.

Imbalanced distribution of group 2 innate lymphoid cells (ILCs) and ILC precursors in peripheral blood of patients with primary biliary cholangitis.

Innate lymphoid cells (ILCs), a novel group of innate immune cells, play a key role in the early immune response via rapidly reacting to signals expressed by tissue-resident cells. ILCs contribute to some autoimmune diseases. We aim to investigate the proportions of circulating ILC subgroups in patients with primary biliary cholangitis (PBC). Overall, 48 patients with PBC and 24 healthy controls (HCs) were enrolled. Circulating ILCs and cytokine production were detected by flow cytometry. The proportions of total ILCs, ILC precursors (ILCPs) and ILCP/ILC2 ratio increased and that of ILC2s decreased in patients with PBC. ILC2 proportion was negatively correlated with gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The proportion of ILCPs and ILCP/ILC2 ratio were positively correlated with alkaline phosphatase, GGT, ALT and AST. ILC2 proportion was significantly decreased in the ursodeoxycholic acid (UDCA) -non-responder group compared with the UDCA-responder group, whereas the proportion of ILCPs and ILCP/ILC2 were ratio significantly increased. The proportions of CD38+ ILC2s, CD38+ ILCPs, CD45RO+ ILC2s and CD45RO+ ILCPs were significantly higher in patients with PBC than in HCs. Levels of IL-17A producing ILCs were higher in patients with PBC than in HCs. PBC is accompanied by alterations in circulating ILCs. The proportions of ILC2s, ILCPs, and ILCP/ILC2 ratio were associated with the PBC disease activity. The proportions of ILCPs and ILCP/ILC2 ratio may reflect the UDCA treatment failure in patients with PBC. ILC2s and ILCPs from patients with PBC get activated, these cells may be involved in the pathogenesis of PBC.

Roles of biomarkers in anti-MDA5-positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5+ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5+ DM-RPILD is unclear. Although some MDA5+ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5+ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected. METHODS: Recent relative studies related to blood biomarkers in PubMed were reviewed. RESULTS: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5+ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5+ DM-ILD and MDA5+ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5+ DM, MDA5+ DM-ILD, and MDA5+ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5+ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD. CONCLUSIONS: Therefore, this review may provide insight to guide treatment decisions for MDA5+ DM-RPILD patients and improve outcomes.

Comprehensive analysis of immunoglobulin and clinical variables identifies functional linkages and diagnostic indicators associated with Behcet's disease patients receiving immunomodulatory treatment.

BACKGROUND: Behcet's disease (BD) is a relapsing systemic vascular autoimmune/inflammatory disease. Despite much effort to investigate BD, there are virtually no unique laboratory markers identified to help in the diagnosis of BD, and the pathogenesis is largely unknown. The aim of this work is to explore interactions between different clinical variables by correlation analysis to determine associations between the functional linkages of different paired variables and potential diagnostic biomarkers of BD. METHODS: We measured the immunoglobulin proteome (IgG, IgG1-4, IgA, IgA1-2) and 29 clinical variables in 66 healthy controls and 63 patients with BD. We performed a comprehensive clinical variable linkage analysis and defined the physiological, pathological and pharmacological linkages based on the correlations of all variables in healthy controls and BD patients without and with immunomodulatory therapy. We further calculated relative changes between variables derived from comprehensive linkage analysis for better indications in the clinic. The potential indicators were validated in a validation set with 76 patients with BD, 30 healthy controls, 18 patients with Takayasu arteritis and 18 patients with ANCA-associated vasculitis. RESULTS: In this study, the variables identified were found to act in synergy rather than alone in BD patients under physiological, pathological and pharmacological conditions. Immunity and inflammation can be suppressed by corticosteroids and immunosuppressants, and integrative analysis of granulocytes, platelets and related variables is likely to provide a more comprehensive understanding of disease activity, thrombotic potential and ultimately potential tissue damage. We determined that total protein/mean corpuscular hemoglobin and total protein/mean corpuscular hemoglobin levels, total protein/mean corpuscular volume, and plateletcrit/monocyte counts were significantly increased in BD compared with controls (P < 0.05, in both the discovery and validation sets), which helped in distinguishing BD patients from healthy and vasculitis controls. Chronic anemia in BD combined with increased total protein contributed to higher levels of these biomarkers, and the interactions between platelets and monocytes may be linked to vascular involvement. CONCLUSIONS: All these results demonstrate the utility of our approach in elucidating the pathogenesis and in identifying novel biomarkers for autoimmune diseases in the future.

Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID-19. METHODS: Studies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta-analysis was performed to compare the ferritin level between different patient groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation. RESULTS: A total of 52 records involving 10 614 COVID-19-confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta-analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non-severe patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. CONCLUSIONS: Ferritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.

Analysis of myositis autoantibodies in Chinese patients with cancer-associated myositis.

BACKGROUND: Cancer-associated myositis (CAM) has poor prognosis and causes higher mortality. In general, myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) have been shown to be useful biomarkers for its diagnosis. METHODS: In the present study, focus was given in assessing the presence, prevalence, and diagnostic values of myositis autoantibodies in Chinese patients diagnosed with CAM. The sera collected from 49 CAM patients, 108 dermatomyositis/polymyositis (DM/PM) patients without cancer, 105 disease controls, and 60 healthy controls were detected for the presence of 16 autoantigens (Jo-1, OJ, EJ, PL-7, PL-12, MDA5, TIF1γ, Mi-2α, Mi-2ß, SAE1, NXP2, SRP, Ku, PM-Scl75, PM-Scl100, and Ro-52) using a commercial Euroline assay. RESULTS: The frequency of anti-TIF1γ was significantly higher in CAM patients than in DM/PM patients without cancer (46.9% vs 14.8%, P < .001). Importantly, the sensitivity and specificity for this MSA were 46.9% and 85.2%, respectively. These helped to differentiate CAM patients from DM/PM patients without cancer. However, there was no difference in other MSAs and MAAs between CAM and DM/PM patients without cancer. CONCLUSION: The present study indicates that anti-TIF1γ levels can serve as important biomarkers for CAM diagnosis and help in distinguishing between CAM and DM/PM patients without cancer.

[Efficiency Characteristics and Evolution Patterns of Urban Carbon Metabolism of Production-Living-Ecological Space in Beijing-Tianjin-Hebei Region].

This study explored the carbon metabolism efficiency of a production-living-ecological space system, which is of great significance for regional factor integration and spatial optimization. In this study, the material flow analysis method was introduced to establish a framework for evaluating the carbon metabolism efficiency of the production-living-ecological space system, and the super-efficiency DEA model and Malmquist index were used to empirically analyze the spatio-temporal distribution, dynamic change, and evolution patterns of the carbon metabolism efficiency of production-living-ecological space in the Beijing-Tianjin-Hebei Region, China, from 2000 to 2020 on the basis of the urban metabolic perspective. The results showed that:① the carbon metabolism efficiency of the production-living-ecological space showed a fluctuating growth trend, indicating the significant spatial differentiation of carbon metabolism efficiency in each city. There was a low overall carbon metabolism efficiency level, with a distribution pattern of being high in the middle and low in the north and south. ② The Malmquist index showed that the Total Factor Productivity (TFP) of carbon metabolism efficiency was greater than 1, and both the Technical Change (TC) and Pure Efficiency Change (PEC) were less than 1, in which the TFP showed an increasing trend, whereas there was no significant contribution of technological progress or pure technical efficiency to carbon metabolism efficiency. The total factor productivity of more than 50% of the cities showed an improving trend, only 38.46% of which made technological progress in improving carbon metabolism efficiency, and more than half of the urban pure technical efficiency showed a decreasing trend, in which the technical efficiency change and scale efficiency change were greater than 1 in most cities. ③ There were different types of carbon efficiency characteristics in each city, and according to the movement rules of the corresponding points in the quartile map, the evolution patterns of tourism industry efficiency were classified into stable, reciprocating, progressive, and abrupt. Therefore, local governments should adopt differentiated strategies to reasonably allocate spatial resources of production-living-ecological space and improve the technical level and scale efficiency, so as to improve the efficiency of urban carbon metabolism.

Effects of brief mindfulness training on smoking cue-reactivity in tobacco use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of Tobacco Use Disorder (TUD) represents a significant and pressing global public health concern, with far-reaching and deleterious consequences for individuals, communities, and healthcare systems. The craving caused by smoking cue is an important trigger for relapse, fundamentally hindering the cessation of cigarette smoking. Mindfulness interventions focusing on cue-reactivity was effective for the treatment of related dependence. Brief mindfulness training (BMT) meets the short-term needs for intervention but the effects still need to be examined. The objective of the present study is to investigate the impact of BMT intervention on smoking cue-reactivity among Chinese college students with TUD, to uncover the dynamic models of brain function involved in this process. METHOD: A randomized control trial (RCT) based on electroencephalography (EEG) was designed. We aim to recruit 90 participants and randomly assign to the BMT and control group (CON) with 1:1 ratio. A brief mindfulness training will be administered to experimental group. After the intervention, data collection will be conducted in the follow-up stage with 5 timepoints of assessments. EEG data will be recorded during the smoking cue-reactivity task and 'STOP' brief mindfulness task. The primary outcomes include subjective reports of smoking craving, changes in EEG indicators, and mindfulness measures. The secondary outcomes will be daily smoking behaviours, affect and impulsivity, as well as indicators reflecting correlation between mindfulness and smoking cue-reactivity. To evaluate the impact of mindfulness training, a series of linear mixed-effects models will be employed. Specifically, within-group effects will be examined by analysing the longitudinal data. Additionally, the effect size for all statistical measurements will be reported, offering a comprehensive view of the observed effects. DISCUSSION: The current study aims to assess the impact of brief mindfulness-based intervention on smoking cue-reactivity in TUD. It also expected to enhance our understanding of the underlying processes involved in brain function and explore potential EEG biomarkers at multiple time points. TRIAL REGISTRATION: Trial registration number: ChiCTR2300069363, registered on 14 March 2023. Protocol Version 1.0., 10 April 2023.

Immune cells and related cytokines in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a non-ischemic cardiomyopathy involving one or more underlying etiologies. It is characterized by structural and functional dysfunction of the myocardium, potentially leading to fibrosis and ventricular remodeling, and an elevated risk of heart failure (HF). Although the pathogenesis of DCM remains unknown, compelling evidence suggests that DCM-triggered immune cells and inflammatory cascades play a crucial role in the occurrence and development of DCM. Various factors are linked to myocardial damage, inducing aberrant activation of the immune system and sustained inflammatory responses in DCM. The investigation of the immunopathogenesis of DCM also contributes to discovering new biomarkers and therapeutic targets. This review examines the roles of immune cells and related cytokines in DCM pathogenesis and explores immunotherapy strategies in DCM.

Significance of immunoglobulins synthesis with central nervous system involvement in Neuro-Behçet's disease.

OBJECTIVES: Demyelination and immunocyte-infiltrated lesions have been found in neuro-Behçet's disease (NBD) pathology. Lacking satisfying laboratory biomarkers in NBD impedes standard clinical diagnostics. We aim to explore the ancillary indicators for NBD diagnosis unveiling its potential etiology. METHODS: 28 NBD with defined diagnosis, 29 patients with neuropsychiatric lupus erythematosus, 30 central nervous system idiopathic inflammatory demyelination diseases (CNS-IIDD), 30 CNS infections, 30 cerebrovascular diseases, and 30 noninflammatory neurological diseases (NIND) were retrospectively enrolled. Immunoglobulins (Ig) in serum and cerebral spinal fluid (CSF) were detected by immunonephelometry and myelin basic protein (MBP) by quantitative enzyme-linked immunosorbent assay. RESULTS: IgA index is almost twice enhanced in NBD than NIND with an accuracy of 0.8488 in differential diagnosis, the sensitivity and specificity of which were 75.00 % and 90.00 % when the cutoff was > 0.6814. The accuracy of CSF Ig and quotient of Ig all exceed 0.90 in discerning NBD with damaged and intact blood-brain barrier (BBB). Clustering analyses divided NBD into two different phenotypes: one with BBB damage has lower Ig synthesis, the other with extra-synthesis in parenchymal sites but with intact BBB. MBP index is significantly correlated with kappa (KAP) index and lambda (LAM) index (r = 0.358, 0.575, P < 0.001), hinting the NBD pathogenesis of CNS demyelination in triggering excessive intrathecal Ig productions and humoral responses. CONCLUSIONS: IgA index acts as a potential diagnostic indicator in differentiating NBD from NIND and CNS-IIDD. Excessive immunoglobulin production induced by CNS inflammation and demyelination might be latent immunopathogenesis of NBD.

Chemokines and chemokine receptors in Behçet's disease.

Behçet's disease (BD), a chronic vascular inflammatory disease, is characterized by the symptoms of ocular lesions, recurrent genital and oral ulcers, skin symptoms and arthritis in addition to neurological, intestinal and vascular involvement. The pathogenesis of BD is poorly understood, and there are no effective laboratory markers for the diagnosis of BD. In addition, BD is presently incurable. Chemokines, a family of small secreted chemotactic cytokines, interact with chemokine receptors and mediate the migration, localization and cellular interactions of inflammatory cells. Several studies have suggested that chemokines and their receptors play an important role in the occurrence and development of BD and that these chemokines along with their receptors can be utilized as biomarkers and therapeutic targets. In the present review, chemokines and chemokine receptors involved in BD and their potential application in diagnosis and therapy have been discussed.