CD8 + CD103 + iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis.

The occurrence of acute kidney injury (AKI) is elevated, one of the main causes is ischemia-reperfusion (I/R). However, no specific therapy is currently available to treat I/R-induced AKI (I/R-AKI). Treg cells have been demonstrated to perform an anti-inflammatory role in a range of autoimmune and inflammatory illnesses. However, there is limited available information about the possible functions of CD8 + CD103 + iTregs in I/R-AKI. We utilized renal tubular epithelial cells (RTECs) subjected to hypoxia-reoxygenation (H/R) and I/R-AKI mouse model to investigate whether CD8 + CD103 + iTregs could attenuate AKI and the underlying mechanism. In vitro, co-cultured with CD8 + CD103 + iTregs alleviated H/R-induced cell injury. After treatment of CD8 + CD103 + iTregs rather than control cells, a significant improvement of I/R-AKI was observed in vivo, including decreased serum creatinine (sCr) and blood urea nitrogen (BUN) levels, reduced renal pathological injury, lowered tubular apoptosis and inhibition of the transition from AKI to chronic kidney disease (CKD). Mechanically, CD8 + CD103 + iTregs alleviated H/R-induced cell injury and I/R-AKI partly by suppressing RTECs pyroptosis via inhibiting the NLRP3/Caspase-1 axis. Our study provides a novel perspective on the possibility of CD8 + CD103 + iTregs for the treatment of I/R-AKI.

Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis.

Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular basement membrane crescentic glomerulonephritis (anti-GBM CGN). However, whether macrophages mediate anti-GBM CGN via MIF-dependent mechanism remains unexplored, which was investigated in this study by specifically deleting MIF from macrophages in MIFf/f-lysM-cre mice. We found that compared to anti-GBM CGN induced in MIFf/f control mice, conditional ablation of MIF in macrophages significantly suppressed anti-GBM CGN by inhibiting glomerular crescent formation and reducing serum creatinine and proteinuria while improving creatine clearance. Mechanistically, selective MIF depletion in macrophages largely inhibited renal macrophage and T cell recruitment, promoted the polarization of macrophage from M1 towards M2 via the CD74/NF-κB/p38MAPK-dependent mechanism. Unexpectedly, selective depletion of macrophage MIF also significantly promoted Treg while inhibiting Th1 and Th17 immune responses. In summary, MIF produced by macrophages plays a pathogenic role in anti-GBM CGN. Targeting macrophage-derived MIF may represent a novel and promising therapeutic approach for the treatment of immune-mediated kidney diseases.

Interference of hemoglobin variants with HbA1c measurements by six commonly used HbA1c methods.

BACKGROUND: Glycated hemoglobin, or hemoglobin A1c (HbA1c), serves as a crucial marker for diagnosing diabetes and monitoring its progression. We aimed to assess the interference posed by common Hb variants on popular HbA1c measurement systems. METHODS: A total of 63 variant and nonvariant samples with target values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-calibrated methods were included. We assessed 6 methods for measuring HbA1c in the presence of HbS, HbC, HbD, HbE, and fetal hemoglobin (HbF): 2 cation-exchange high-performance liquid chromatography (HPLC) methods (Bio-Rad D-100 and HLC-723 G8), a capillary electrophoresis (CE) method (Sebia Capillarys 3 TERA), an immunoassay (Roche c501), an enzyme assay system (Mindray BS-600M), and a boronate affinity method (Primus Premier Hb9210). RESULTS: The HbA1c results for nonvariant samples from the 6 methods were in good agreement with the IFCC-calibrated method results. The Bio-Rad D-100, Capillarys 3, Mindray BS-600M, Premier Hb9210, and Roche c501 showed no interference from HbS, HbC, HbD, and HbE. Clinically significant interference was observed for the HLC-723 G8 standard mode. Elevated HbF levels caused significant negative biases for all 6 methods, which increased with increasing HbF concentration. CONCLUSION: Elevated levels of HbF can severely affect HbA1c measurements by borate affinity, immunoassays, and enzyme assays.

Analytical performance evaluation of the Mindray enzymatic assay for hemoglobin A1c measurement.

Hemoglobin A1c (HbA1c) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA1c measurement. The performance of the enzymatic method, including precision, accuracy, and linearity, was evaluated. Moreover, the interference effect from conventional interferents, Hb derivatives, Hb variants, and common drugs were assessed. In addition, the agreement of HbA1c results was compared between enzymatic methods, cation-exchange high-performance liquid chromatography (HPLC), and immunoassays. The intra-assay, between-assay, and total precision of HbA1c were all lower than 2%. HbA1c showed good linearity within the range of 3.96-20.23%. The enzymatic assay yielded results consistent with the external quality control samples, with a bias of less than ± 6% from the target values. The enzymatic method showed no interference from bilirubin, intralipid, vitamin C, Hb derivatives, common Hb variants, as well as antipyretic analgesics and hypoglycemic drugs. The HbA1c results of the enzymatic assay showed good agreement and accuracy compared to those obtained from the HPLC method and the immunoassay. The enzymatic method kit performed on the BS-600M chemistry analyzer is a reliable and robust method for measuring HbA1c. It is suitable for routine practice in clinical chemistry laboratories.

Prevalence of monoclonal gammopathy of undetermined significance in Shenzhen, China.

BACKGROUND: Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population. METHODS: This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein. RESULTS: A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08-1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04-2.50). The prevalence of MGUS was significantly higher in males than in females (P < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively. CONCLUSIONS: The prevalence of MGUS is substantially lower in southern China than in whites and blacks.

Compound heterozygous with Hb G-Taipei and Hb Lepore-Boston-Washington: An unexpected finding triggered by HbA1c measurement.

Background: Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA1c analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management. Case report: In this study, we present the case of a 23-year-old man with undetectable HbA1c levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA1c absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of ß-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del). Conclusion: The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA1c analysis.

Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods.

OBJECTIVES: The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. METHODS: Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. RESULTS: All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to -3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to -2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to -3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. CONCLUSIONS: The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.

Incidence and risk factors of acute kidney injury after transcatheter aortic valve replacement.

PURPOSE: Acute kidney injury (AKI) is a common early complication secondary to transcatheter aortic valve replacement (TAVR). Studies on the incidence and risk factors for AKI after TAVR surgery are limited to date. Here, we retrospectively analyzed the incidence and risk factors for AKI after TAVR surgery in our hospital. MATERIALS AND METHODS: Patients who underwent TAVR surgery at our hospital from November 2017 to February 2023 were selected. AKI was defined using the 2012 KDIGO definition and staging criteria. The relevant data and information between the AKI group and the non-AKI group were compared and analyzed, and a binary logistic regression model was used to analyze the risk factors for AKI. RESULTS: A total of 75 patients who underwent TAVR surgery were included in the retrospective analysis. After TAVR, the incidence of AKI was 17.3% (13/75), of which 8 (61.5%) had stage 1 AKI, 2 (15.4%) had stage 2 AKI, 3 (23.1%) had stage 3 AKI, and 3 needed renal replacement therapy. After multivariate logistic analysis, contrast volume (OR = 1.024 (1.001, 1.047)) was found to be an independent risk factor for AKI, while patients with high estimated glomerular filtration rate (eGFR) (OR = 0.903 (0.826, 0.986)) have a reduced risk of AKI. CONCLUSION: A retrospective study revealed a 17.3% incidence of AKI after TAVR surgery in our hospital, most of which were stage 1 AKI. A low preoperative eGFR and contrast volume were found to be independent risk factors for AKI.

Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing.

Lung cancer stands as the predominant cause of cancer-related mortality globally. Lung adenocarcinoma (LUAD), being the most prevalent subtype, garners extensive attention due to its notable heterogeneity, which significantly influences tumor development and treatment approaches. This research leverages single-cell RNA sequencing (scRNA-seq) datasets to delve into the impact of KRAS/TP53 co-mutation status on LUAD. Moreover, utilizing the TCGA-LUAD dataset, we formulated a novel predictive risk model, comprising seven prognostic genes, through LASSO regression, and subjected it to both internal and external validation sets. The study underscores the profound impact of KRAS/TP53 co-mutational status on the tumor microenvironment (TME) of LUAD. Crucially, KRAS/TP53 co-mutation markedly influences the extent of B cell infiltration and various immune-related pathways within the TME. The newly developed predictive risk model exhibited robust performance across both internal and external validation sets, establishing itself as a viable independent prognostic factor. Additionally, in vitro experiments indicate that MELTF and PLEK2 can modulate the invasion and proliferation of human non-small cell lung cancer cells. In conclusion, we elucidated that KRAS/TP53 co-mutations may modulate TME and patient prognosis by orchestrating B cells and affiliated pathways. Furthermore, we spotlight that MELTF and PLEK2 not only function as prognostic indicators for LUAD, but also lay the foundation for the exploration of innovative therapeutic approaches.

Identification of Hb Lepore, Hb anti-Lepore, and α-globin gene triplications by long-read single-molecule real-time sequencing.

OBJECTIVES: Hemoglobin (Hb) Lepore and Hb anti-Lepore are infrequent fusion gene variants that result from nonhomologous crossovers during meiosis. Conventional molecular testing methods may face challenges in identifying these variants. During Hb analysis using capillary electrophoresis, we encountered 6 cases with unusual Hb variants. Our aim was to identify the alterations in their globin genes. METHODS: Gap-polymerase chain reaction (PCR), reverse dot-blot assay (RDB), Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-read single-molecule real-time (SMRT) sequencing were used to confirm the presence of globin gene alterations. RESULTS: The routine thalassemia gene test kit using the gap-PCR and RDB techniques did not detect common gene variations. Direct sequencing failed to identify any known or unknown globin gene alterations. The MLPA analysis, however, revealed the possible presence of α-globin gene triplications as well as 2 types of fusion gene alterations. Further analysis using long-read SMRT sequencing accurately identified 3 rare gene variations: αααanti-3.7, Hb Lepore-Boston-Washington, and Hb anti-Lepore P-India. CONCLUSIONS: Conventional methods may overlook rare thalassemias or Hb variants. Long-read SMRT sequencing has the potential to identify breakpoints in fusion genes, demonstrating that it is a promising technique for detecting rare thalassemias.

Validation of COPD Population Screener Questionnaire in Chinese Population: A National Multicenter Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is highly prevalent and underdiagnosed worldwide. The validity and reliability of COPD Population Screening (COPD-PS) questionnaire are not properly known in a large-sample Chinese population. METHODS: This is a national multicenter prospective study that enrolled 1,824 outpatients from 12 hospital sites in China. Scores of the Chinese version of COPD-PS questionnaire, demographic data, and clinical information were collected. The validity and the test-retest reliability were evaluated. RESULTS: 1,824 participants were involved in this study, and 404 (22.1%) were diagnosed with COPD. The overall area under the curve (AUC) of the receiver operating characteristic (ROC) for COPD-PS questionnaire was 0.761 (95% CI: 0.734-0.787). A cut-off point of 4 was recommended, corresponding to a sensitivity of 74.50% and a specificity of 64.37%. The COPD-PS questionnaire showed an overall Pearson's correlation of 0.88. CONCLUSIONS: The COPD-PS questionnaire can be used in screening COPD patients from the general Chinese population with respiratory symptoms.

A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS.

In this report we decribed a new α-chain variant found during the measurement of hemoglobin A1c (Hb A1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.

Leveraging senescence-oxidative stress co-relation to predict prognosis and drug sensitivity in breast invasive carcinoma.

Introduction: Female breast cancer has risen to be the most common malignancy worldwide, causing a huge disease burden for both patients and society. Both senescence and oxidative stress attach importance to cancer development and progression. However, the prognostic roles of senescence and oxidative stress remain obscure in breast cancer. In this present study, we attempted to establish a predictive model based on senescence-oxidative stress co-relation genes (SOSCRGs) and evaluate its clinical utility in multiple dimensions. Methods: SOSCRGs were identified via correlation analysis. Transcriptome data and clinical information of patients with breast invasive carcinoma (BRCA) were accessed from The Cancer Genome Atlas (TCGA) and GSE96058. SVM algorithm was employed to process subtype classification of patients with BRCA based on SOSCRGs. LASSO regression analysis was utilized to establish the predictive model based on SOSCRGs. Analyses of the predictive model with regards to efficacy evaluation, subgroup analysis, clinical association, immune infiltration, functional strength, mutation feature, and drug sensitivity were organized. Single-cell analysis was applied to decipher the expression pattern of key SOSCRGs in the tumor microenvironment. Additionally, qPCR was conducted to check the expression levels of key SOSCRGs in five different breast cancer cell lines. Results: A total of 246 SOSCRGs were identified. Two breast cancer subtypes were determined based on SOSCRGs and subtype 1 showed an active immune landscape. A SOSCRGs-based predictive model was subsequently developed and the risk score was clarified as independent prognostic predictors in breast cancer. A novel nomogram was constructed and exhibited favorable predictive capability. We further ascertained that the infiltration levels of immune cells and expressions of immune checkpoints were significantly influenced by the risk score. The two risk groups were characterized by distinct functional strengths. Sugar metabolism and glycolysis were significantly upregulated in the high risk group. The low risk group was deciphered to harbor PIK3CA mutation-driven tumorigenesis, while TP53 mutation was dominant in the high risk group. The analysis further revealed a significantly positive correlation between risk score and TMB. Patients in the low risk group may also sensitively respond to several drug agents. Single-cell analysis dissected that ERRFI1, ETS1, NDRG1, and ZMAT3 were expressed in the tumor microenvironment. Moreover, the expression levels of the seven SOSCRGs in five different breast cancer cell lines were quantified and compared by qPCR respectively. Conclusion: Multidimensional evaluations verified the clinical utility of the SOSCRGs-based predictive model to predict prognosis, aid clinical decision, and risk stratification for patients with breast cancer.

Mutational spectrum of HBD gene in the Chinese population: Description of 36 mutations including 11 novel variants.

INTRODUCTION: Mutations in the hemoglobin subunit delta (HBD) gene (MIM#142000) are associated with decreased levels of the Hemoglobin A2 (Hb A2 ) fraction. We aimed to examine the prevalence of HBD gene mutations and summarize their characteristics in the Chinese population. METHODS: Individuals who exhibited Hb A2 levels below 1.8%, with or without Hb A2 variant peaks, were chosen for further investigation. Hemoglobin analysis was conducted using capillary electrophoresis. Common α and ß-thalassemia in China were detected using gap-PCR and reverse dot blot hybridization. The presence of HBD gene mutations was confirmed by DNA sequencing. RESULTS: A total of 188 patients were identified as carriers of the HBD gene mutation, with a prevalence of approximately 0.46%. We discovered 36 types of mutations, 30 of which resulted in δ-globin variants, while the remaining 6 resulted in δ-thalassemia. The most common mutation was HBD:c.-127 T > C, accounting for 87.2% of δ-thalassemia cases. In addition, we identified 11 novel HBD gene mutations and found 10 cases compounded with other common thalassemias. CONCLUSION: We observed a high prevalence of HBD gene mutations in southern China. Our findings provide a genetic basis for screening for δ-thalassemia and enrich the spectrum of HBD gene mutations.

Myofascial acupuncture versus routine acupuncture for mechanical neck pain: a protocol for a multicentre randomised controlled trial.

INTRODUCTION: Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP. METHODS AND ANALYSIS: The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the 'Sancai-Tianbu' myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200061453.

Prognosis stratification of patients with breast invasive carcinoma based on cysteine metabolism-disulfidptosis affinity.

PURPOSE: The rise of female breast cancer has created a significant global public health issue that requires effective solutions. Disulfidptosis, a recently identified form of cell death characterized by an excessive accumulation of disulfides, has unique initiatory and regulatory mechanisms. The formation of disulfide bonds is a metabolic event typically associated with cysteines. This study aims to explore the potential of the affinity between cysteine metabolism and disulfidptosis in risk stratification for breast invasive carcinoma (BRCA). METHODS: We used correlation analysis to decipher co-relation genes between cysteine metabolism and disulfidptosis (CMDCRGs). Both LASSO regression analysis and multivariate Cox regression analysis were employed to construct the prognostic signature. Additionally, we conducted investigations concerning subtype identification, functional enhancement, mutation landscape, immune infiltration, drug prioritization, and single-cell analysis. RESULTS: We developed and validated a six-gene prognostic signature as an independent prognostic predictor for BRCA. The prognostic nomogram, based on risk score, demonstrated a favorable capability in predicting survival outcomes. We identified distinct gene mutations, functional enhancements, and immune infiltration patterns between the two risk groups. Four clusters of drugs were predicted as potentially effective for patients in the low-risk group. We identified seven cell clusters within the tumor microenvironment of breast cancer, and RPL27A was found to be widely expressed in this environment. CONCLUSION: Multidimensional analyses confirmed the clinical utility of the cysteine metabolism-disulfidptosis affinity-based signature in risk stratification and guiding personalized treatment for patients with BRCA.

High serum immunoglobulin D levels in systemic lupus erythematosus: more to be found?

INTRODUCTION: Many studies have shown that serum immunoglobulin D (IgD) is usually increased in autoimmune diseases. The potential role of IgD in systemic lupus erythematosus (SLE) is still unclear. Our study aimed to compare the serum IgD levels of SLE with different population and to evaluate the relationship between serum IgD and SLE. METHODS: Fifty SLE patients, 40 non-SLE chronic kidney disease (CKD) patients, and 50 healthy volunteers were enrolled in this study. Serum IgD levels were analyzed by ELISA assay and compared between groups. The correlation of serum IgD and SLE disease were evaluated. The ability of serum IgD to predict SLE was analyzed by graphing receiver operating characteristic curves. RESULTS: Serum IgD levels were significantly higher in SLE patients compared to non-SLE CKD and healthy controls (7436.1 ± 5862.1 vs. 4517.8 ± 5255.2 vs. 4180.4 ± 4881 ng/mL, p = 0.01, p = 0.002, respectively), and in patients with high SLE Disease Activity Index (SLEDAI) scores compared with those with low scores (8572.9 ± 5968.7 vs. 5020.4 ± 4972.5 ng/mL, p = 0.044). High level of inflammatory cytokines and decreased circulating basophil counts were found in SLE patients (p < 0.05). No correlations was identified between serum IgD levels and SLEDAI scores (p > 0.05). Serum IgD was noninferior to IgG or IgE in discriminating SLE with an area under the curve of 0.672 (95% CI, 0.59-0.75). CONCLUSIONS: Serum IgD levels are significantly elevated in SLE patients with high SLEDAI scores. Simultaneous occurrence of increased inflammatory cytokines and decreased basophil counts highlights the potential role of IgD-targets interaction in SLE pathogenesis. Key points • Total serum IgD levels were elevated in SLE patients. • High IgD levels were significantly higher in SLE patients with high SLEDAI scores. • The ability of serum IgD was equivalent to IgG or IgE in discriminating SLE from CKD and healthy adult.

Acupuncture May Be a Potential Complementary Therapy for Alzheimer's Disease: A Network Meta-Analysis.

With Alzheimer's disease (AD) becoming a worldwide problem, traditional Chinese medicine (TCM), especially acupuncture, stands out as a complementary therapy because of its feature-"treatment based on syndrome differentiation". This systematic review and network meta-analysis (NMA) confirms the complement effect of acupuncture and explores the best combination of therapy for AD based on the total effect and activity of daily living scale (ADL). We searched relevant randomized controlled trials (RCTs) that applied acupuncture for treating AD. 58 studies with 4334 patients were included in accordance with PRISMA guidelines. The results showed that for the total effect, the order of probability for the effect: acupuncture + western medicine > acupuncture + herbal medicine > acupuncture > acupuncture + western medicine + herbal medicine. For the ADL score, the order of probability for the effect: acupuncture + western medicine > acupuncture > acupuncture + western medicine + herbal medicine > acupuncture + herbal medicine. The combination of acupuncture and medicine has a better clinical effect than acupuncture only in a way. Acupuncture + western medicine has an obvious and exact improvement in the curative effect from both total effect and ADL score, but further higher quality studies, which can detail the classification of these interventions, are still needed to verify it.

Comparability of different methods of glycated hemoglobin measurement for samples of patients with variant and non-variant hemoglobin.

BACKGROUND: Glycated hemoglobin (HbA1c) is measured to monitor patients with diabetes. However, the measurement results can vary according to the analysis method and presence of variant hemoglobin. Thus, we compared HbA1c results between liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). METHODS: %HbA1c were measured using the two methods in 45 non-variant and 73 heterozygous variant samples. Precision was calculated; the results were compared using Passing-Bablok regression and the concordance correlation coefficient (CCC). The average bias between methods was compared with the lowest bias of 2.3% for biological variation. RESULTS: The precision of the two methods was < 2%. The R2 for the non-variant samples were 0.986 and the CCC was 0.99. Based on α- and ß-chain, the variant samples were divided into four groups: α-chain, α-chain negligible, ß-chain, and ß-chain negligible variants. The R2 between the two methods of the four groups were ＞0.95; However, the average biases of α-chain and ß-chain variants were above the minimum bias. CONCLUSION: LC-MS/MS and MALDI-TOF MS had good comparability in the measurement of HbA1c in non-variant samples, but the existence of variant hemoglobin caused discrepancies.

P2Y12 inhibitor clopidogrel inhibits renal fibrosis by blocking macrophage-to-myofibroblast transition.

Clopidogrel, a P2Y12 inhibitor, is a novel anti-fibrosis agent for chronic kidney disease (CKD), but its mechanisms remain unclear, which we investigated by silencing P2Y12 or treating unilateral ureteral obstruction (UUO) in LysM-Cre/Rosa Tomato mice with clopidogrel in vivo and in vitro. We found that P2Y12 was significantly increased and correlated with progressive renal fibrosis in CKD patients and UUO mice. Phenotypically, up to 82% of P2Y12-expressing cells within the fibrosing kidney were of macrophage origin, identified by co-expressing CD68/F4/80 antigens or a macrophage-lineage-tracing marker Tomato. Unexpectedly, more than 90% of P2Y12-expressing macrophages were undergoing macrophage-to-myofibroblast transition (MMT) by co-expressing alpha smooth muscle actin (α-SMA), which was also confirmed by single-cell RNA sequencing. Functionally, clopidogrel improved the decline rate of the estimated glomerular filtration rate (eGFR) in patients with CKD and significantly inhibited renal fibrosis in UUO mice. Mechanistically, P2Y12 expression was induced by transforming growth factor ß1 (TGF-ß1) and promoted MMT via the Smad3-dependent mechanism. Thus, silencing or pharmacological inhibition of P2Y12 was capable of inhibiting TGF-ß/Smad3-mediated MMT and progressive renal fibrosis in vivo and in vitro. In conclusion, P2Y12 is highly expressed by macrophages in fibrosing kidneys and mediates renal fibrosis by promoting MMT via TGF-ß/Smad3 signaling. Thus, P2Y12 inhibitor maybe a novel and effective anti-fibrosis agent for CKD.