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Objective: To investigate the frequencies and subset distribution of peripheral helper (Tph) T cells in patients with immune thrombocytopenia (ITP), and explore the pathogenesis of ITP., Methods: A total of 25 newly diagnosed ITP patients treated in The Second Affiliated Hospital of Dalian Medical University from January to December 2022 were selected, and 25 healthy volunteers (age- and sex-matched) were recruited as the control group. Flow cytometry was used to detect the subsets of CD4 + T cells and Tph cells., Results: The frequency of effector memory (CCR7 - CD45RO + CD4 + ) T cells in ITP patients was significantly higher than that in healthy controls( P < 0.05). The frequency of Tph cells in ITP patients was also significantly higher than that in healthy controls ( P < 0.001), and most of the Tph cells in ITP patients were effector memory T cells. Furthermore, the expressions of T-cell costimulatory molecules in Tph cells, including ICOS and CD84, were similar to those in follicular helper T(Tfh) cells. CXCR3 - CCR6 - Tph (Tph2) subgroup was dominant in Tph cells, but the frequency of CXCR3 + CCR6 - Tph (Tph1) cells in ITP patients was much higher than that in healthy controls ( P < 0.05)., Conclusion: Tph cells, especially Tph1 cells, were abnormally expanded in ITP patients, which may be a potential etiology of ITP.

Objective. The trend in the medical field is towards intelligent detection-based medical diagnostic systems. However, these methods are often seen as 'black boxes' due to their lack of interpretability. This situation presents challenges in identifying reasons for misdiagnoses and improving accuracy, which leads to potential risks of misdiagnosis and delayed treatment. Therefore, how to enhance the interpretability of diagnostic models is crucial for improving patient outcomes and reducing treatment delays. So far, only limited researches exist on deep learning-based prediction of spontaneous pneumothorax, a pulmonary disease that affects lung ventilation and venous return. Approach. This study develops an integrated medical image analysis system using explainable deep learning model for image recognition and visualization to achieve an interpretable automatic diagnosis process. Main results. The system achieves an impressive 95.56% accuracy in pneumothorax classification, which emphasizes the significance of the blood vessel penetration defect in clinical judgment. Significance. This would lead to improve model trustworthiness, reduce uncertainty, and accurate diagnosis of various lung diseases, which results in better medical outcomes for patients and better utilization of medical resources. Future research can focus on implementing new deep learning models to detect and diagnose other lung diseases that can enhance the generalizability of this system., (Creative Commons Attribution license.)

Primary spontaneous pneumothorax (PSP) primarily affects slim and tall young males. Exploring the etiological link between chest wall structural characteristics and PSP is crucial for advancing treatment methods. In this case-control study, chest computed tomography (CT) images from patients undergoing thoracic surgery, with or without PSP, were analyzed using Artificial Intelligence. Convolutional Neural Network (CNN) model of EfficientNetB3 and InceptionV3 were used with transfer learning on the Imagenet to compare the images of both groups. A heatmap was created on the chest CT scans to enhance interoperability, and the scale-invariant feature transform (SIFT) was adopted to further compare the image level. A total of 2,312 CT images of 26 non-PSP patients and 1,122 CT images of 26 PSP patients were selected. Chest-wall apex pit (CAP) was found in 25 PSP and three non-PSP patients (p < 0.001). The CNN achieved a testing accuracy of 93.47 % in distinguishing PSP from non-PSP based on chest wall features by identifying the existence of CAP. Heatmap analysis demonstrated CNN's precision in targeting the upper chest wall, accurately identifying CAP without undue influence from similar structures, or inappropriately expanding or minimizing the test area. SIFT results indicated a 10.55 % higher mean similarity within the groups compared to between PSP and non-PSP (p < 0.001). In conclusion, distinctive radiographic chest wall configurations were observed in PSP patients, with CAP potentially serving as an etiological factor linked to PSP. This study accentuates the potential of AI-assisted analysis in refining diagnostic approaches and treatment strategies for PSP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: To investigate the regulatory effect of interferon-α (IFN-α) on the apoptosis and killing function of CD56 dim CD57 + natural killer (NK) cells in systemic lupus erythematosus (SLE) patients, and to explore the specific mechanism., Methods: A total of sixty-four newly treated SLE patients and sixteen healthy controls (HC) enrolled in the Second Hospital of Dalian Medical University were selected as the research subjects. And the gene expression levels of molecules related to NK cell-killing function were detected by real-time quantitative polymerase chain reaction. CD56 dim CD57 + NK cells were co-cultured with the K562 cells, and the apoptotic K562 cells were labeled with Annexin-Ⅴ and 7-amino-actinomycin D. Peripheral blood mononuclear cells were treated with 20, 40, and 80 μmol/L hydrogen peroxide (H 2 O 2 ), and treated without H 2 O 2 as control, the expression level of perforin (PRF) was detected by flow cytometry. The concentration of IFN-α in serum was determined by enzyme linked immunosorbent assay. The expression levels of IFN-α receptors (IFNAR) on the surface of CD56 dim CD57 + NK cells were detected by flow cytometry, and were represented by mean fluorescence intensity (MFI). CD56 dim CD57 + NK cells were treated with 1 000 U/mL IFN-α for 24, 48 and 72 h, and no IFN-α treatment was used as the control, the apoptosis and the expression levels of mitochondrial reactive oxygen species (mtROS) were measured by flow cytometry and represented by MFI., Results: Compared with HC( n =3), the expression levels of PRF1 gene in peripheral blood NK cells of the SLE patients ( n =3) were decreased (1.24±0.41 vs . 0.57±0.12, P =0.05). Compared with HC( n =5), the ability of peripheral blood CD56 dim CD57 + NK cells in the SLE patients ( n =5) to kill K562 cells was significantly decreased (58.61%±10.60% vs . 36.74%±6.27%, P < 0.01). Compared with the control ( n =5, 97.51%±1.67%), different concentrations of H 2 O 2 treatment significantly down-regulated the PRF expression levels of CD56 dim CD57 + NK cells in a dose-dependent manner, the 20 μmol/L H 2 O 2 PRF was 83.23%±8.48% ( n =5, P < 0.05), the 40 μmol/L H 2 O 2 PRF was 79.53%±8.56% ( n =5, P < 0.01), the 80 μmol/L H 2 O 2 PRF was 76.67%±7.16% ( n =5, P < 0.01). Compared to HC ( n =16), the serum IFN-α levels were significantly increased in the SLE patients ( n =45) with moderate to high systemic lupus erythematosus disease activity index (SLEDAI≥10) [(55.07±50.36) ng/L vs . (328.2±276.3) ng/L, P < 0.001]. Meanwhile, compared with HC ( n =6), IFNAR1 expression in peripheral blood CD56 dim CD57 + NK cells of the SLE patients ( n =6) were increased (MFI: 292.7±91.9 vs . 483.2±160.3, P < 0.05), and compared with HC ( n =6), IFNAR2 expression in peripheral blood CD56 dim CD57 + NK cells of the SLE patients ( n =7) were increased (MFI: 643.5±113.7 vs . 919.0±246.9, P < 0.05). Compared with control ( n =6), the stimulation of IFN-α ( n =6) significantly promoted the apoptosis of CD56 dim CD57 + NK cells (20.48%±7.01% vs . 37.82%±5.84%, P < 0.05). In addition, compared with the control ( n =4, MFI: 1 049±174.5), stimulation of CD56 dim CD57 + NK cells with IFN-α at different times significantly promoted the production of mtROS in a time-dependent manner, 48 h MFI was 3 437±1 472 ( n =4, P < 0.05), 72 h MFI was 6 495±1 089 ( n =4, P < 0.000 1), but there was no significant difference at 24 h of stimulation., Conclusion: High serum IFN-α level in SLE patients may induce apoptosis by promoting mtROS production and inhibit perforin expression, which can down-regulate CD56 dim CD57 + NK killing function.

Increasing evidence shows that metabolic factors are involved in the pathological process of osteoarthritis (OA). Lactate has been shown to contribute to the onset and progression of diseases. While whether lactate is involved in the pathogenesis of OA through impaired chondrocyte function and its mechanism remains unclear. This study confirmed that serum lactate levels were elevated in OA patients compared to healthy controls and were positively correlated with synovial fluid lactate levels, which were also correlated with fasting blood glucose, high-density lipoprotein, triglyceride. Lactate treatment could up-regulate expressions of the lactate receptor hydroxy-carboxylic acid receptor 1 (HCAR1) and lactate transporters in human chondrocytes. We demonstrated the dual role of lactate, which as a metabolite increased NADPH levels by shunting glucose metabolism to the pentose phosphate pathway, and as a signaling molecule up-regulated NADPH oxidase 4 (NOX4) via activating PI3K/Akt signaling pathway through receptor HCAR1. Particularly, lactate could promote reactive oxygen species (ROS) generation and chondrocyte damage, which was attenuated by pre-treatment with the NOX4 inhibitor GLX351322. We also confirmed that lactate could increase expression of catabolic enzymes (MMP-3/13, ADAMTS-4), reduce the synthesis of type II collagen, promote expression of inflammatory cytokines (IL-6, CCL-3/4), and induce cellular hypertrophy and aging in chondrocytes. Subsequently, we showed that chondrocyte damage mediated by lactate could be reversed by pre-treatment with N-Acetyl-l-cysteine (NAC, ROS scavenger). Finally, we further verified in vivo that intra-articular injection of lactate in Sprague Dawley (SD) rat models could damage cartilage and exacerbate the progression of OA models that could be countered by the NOX4 inhibitor GLX351322. Our study highlights the involvement of lactate as a metabolic factor in the OA process, providing a theoretical basis for potential metabolic therapies of OA in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The predictive value of hemoglobin A1c (HbA1c) levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) is still controversial. This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease (CAD) who had undergone PCI by performing a meta-analysis of cohort studies., Methods: This meta-analysis included non-diabetic patients with CAD who had undergone PCI. A systematic search for publications listed in the PubMed, Embase, and Cochrane Library databases from commencement to December 2018 was conducted. Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible. The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events, and the secondary outcome was short-term all-cause deaths. The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0. Odds ratios (ORs) were pooled using a random or fixed-effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary., Results: Six prospective cohort studies involving 10,721 patients met the inclusion criteria. From the pooled analysis, abnormal HbA1c levels were associated with increased risk for long-term all-cause death (OR 1.39, 95% confidence interval [CI] 1.16-1.68, P = 0.001, I = 45%). Sub-group analysis suggested that abnormal HbA1c levels between 6.0% and 6.5% predicted higher long-term major adverse cardiac event (including all-cause deaths, non-fatal myocardial infarction, target lesion revascularization, target vessel revascularization, recurrent acute myocardial infarction, heart failure requiring hospitalization, and stent thrombosis) risk (OR 2.05, 95% CI 1.46-2.87, P < 0.001, I = 0). Contrarily, elevated HbA1c levels were not associated with increased risk of short-term all-cause death (OR 1.16, 95% CI 0.88-1.54, P = 0.300, I = 0)., Conclusions: An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI. Strict control of HbA1c levels may improve patient survival. Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The focal ratio degradation (FRD) of optical fiber is one of major sources causing light loss in multi-fiber astronomical instruments. Meanwhile, the sky subtraction is crucial to multi-fiber spectra reduction, especially for the objects which are as faint as the sky background, not to mention for those even fainter ones. To improve the accuracy of sky subtraction, it is necessary to normalize the throughput among object fibers and sky sampling fibers. The rotation and twist during mounting and rotating could change the FRD of individual fibers, which means the variation of the transmission throughput among fibers. We investigate such throughput variation among LAMOST fibers and its correlation with the intensity of sky emission lines on all wavelength coverage in this paper. On the basis of this work, we present an approach to correcting the varied fiber throughput by measuring the intensity of the sky emission lines as the secondary throughput correction. This approach has been applied to LAMOST 2D Pipeline.

Malaria situation in 5 monitoring sites of Yunnan showed a decline trend from 2005 to 2008. The average malaria incidence in 2008 was 11.84/10,000 with a decrease of 66.1% in comparison to 2005. The seropositive rate with immuno-fluorescence assay (IFA) was 4.61% for pupils. 82% of the cases chose town or township hospitals as the first place of seeking diagnosis and treatment. 83.6% cases were diagnosed over 3 days of symptom appearing. The main clinical manifestation was fever every other day attack (occupied 72.7%). 98.4% of the cases were with light symptoms. The proportion of primary attacks and relapses among malaria patients were 95.3% and 4.7%, respectively. Plasmodium vivax was the main malaria parasite, occupying 81.2%. 97.2% of the local infected cases were found in the bordering areas of the country. The mosquito net utilization rate was 51.4%. Results showed that malaria has been effectively controlled in the monitoring sites of Yunnan.

Objective: To detect the KChIP2 mRNA level in rheumatic heart disease patients with or without atrial fibrillation (AF) by real-time PCR., Methods: Right atrial appendage samples from rheumatic heart disease patients with (n = 17) or without AF (n = 13) were obtained during cardiac surgery. Total RNA was extracted from the atrial tissues, and the KChIP2 and Kv4.3 mRNA were detected by SYBR Green I real-time PCR with the GAPDH as the house keeping gene., Result: The ratio of KChIP2/GAPDH (0.1468 +/- 0.0452 vs. 0.2200 +/- 0.0388, P<0.01) and the ratio of Kv4.3/GAPDH (0.3946 +/- 0.1826 vs. 0.5257 +/- 0.1427, P<0.05) were significantly lower in AF patients compared to non-AF patients., Conclusion: Down-regulated atrial KChIP2 and Kv4.3 mRNA expressions in rheumatic heart disease patients with chronic AF might be one of the molecular bases responsible for the down-regulation of the I(to) current density of AF.