[Objective] To explore the effectiveness of applying the PDCA (Plan-Do-Check-Act) cycle to enhance the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients across multiple hospital campuses. [Methods] Clinical blood transfusion data from May to July 2022 were selected. Specific improvement measures were formulated based on the survey results, and the PDCA cycle management model was implemented from August 2022. The post-intervention phase spanned from August 2022 to October 2023. The Rh phenotype compatibility rate, the detection rate of Rh system antibodies, and the proportion of Rh system antibodies among unexpected antibodies were compared between the pre-intervention phase (May to July 2022) and the post-intervention phase. [Results] After the continuous improvement with the PDCA cycle, the compatibility rate for the five Rh blood group antigen phenotypes between donors and recipients from August to October 2023 reached 81.90%, significantly higher than the 70.54% recorded during the pre-intervention phase (May to July 2022, P<0.01), and displayed a quarterly upward trend (β=0.028, P<0.05). The detection rate of Rh blood group system antibodies (β=-9.839×10^-5, P<0.05) and its proportion among all detected antibodies (β=-0.022, P<0.05) showed a quarterly decreasing trend, both demonstrating a negative correlation with the enhanced compatibility rate (r values of -0.981 and -0.911, respectively; P<0.05). [Conclusion] The implementation of targeted measures through the PDCA cycle can effectively increase the compatibility rate of five Rh blood group antigen phenotypes between donors and recipients, reduce the occurrence of unexpected Rh blood group antibodies, thereby lowering the risk of transfusion and enhancing the quality and safety of medical care.

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Objective: To evaluate the effectiveness and safety of the tonifying spleen and reinforcing Qi (TSRQ) therapy combined with thyroid hormone replacement therapy (THRT) for treating Hashimoto’s hypothyroidism. Methods: From database foundation to January 14, 2025, PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (VIP), and China Biomedical Literature Database (CBM) were searched for relevant information. Randomized clinical trials (RCTs) evaluating the efficacy and safety of TSRQ therapy combined with THRT for Hashimoto’s hypothyroidism were eligible for inclusion. Following quality assessment, data were analyzed using Stata 15.1 to conduct a meta-analysis and systematic review. Subgroup analysis was used to identify the sources of heterogeneity. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to evaluate the certainty of the evidence. Results: This study included 30 RCTs, comprising 2 687 patients with Hashimoto’s hypothyroidism. Overall methodological quality was acceptable, with no studies exhibiting a high risk of bias. Meta-analysis demonstrated that TSRQ therapy combined with THRT significantly enhanced serum free triiodothyronine (fT3) levels [standardized mean difference (SMD) = 0.76, 95% confidence interval (CI): 0.57 to 0.94, P < 0.001] and free thyroxine (fT4) levels (SMD = 0.86, 95% CI: 0.61 to 1.11, P < 0.001), while reducing thyroid-stimulating hormone (TSH) levels (SMD = – 0.99, 95% CI: – 1.20 to – 0.78, P < 0.001) compared with THRT alone. Furthermore, the combination therapy significantly decreased anti-thyroid peroxidase antibody (TPOAb) levels (SMD = – 1.46, 95% CI: – 1.79 to – 1.13, P < 0.001) and anti-thyroglobulin antibody (TgAb) levels (SMD = – 1.46, 95% CI: – 1.80 to – 1.11, P < 0.001). TSRQ therapy did not adversely impact the safety profile of THRT. However, while some sources of heterogeneity have been identified (e.g., specific detection methodologies, I² = 0.0%, P = 0.938), there remains a portion of unexplained heterogeneity (e.g., publication year, I² = 93.4%, P < 0.001), which has undermined confidence in these pooled estimates. The evidence ratings for fT3, fT4, and TSH were limited, and those for TPOAb and TgAb were even more limited. Conclusion TSRQ therapy combined with THRT may strengthen thyroid function and modulate immune dysregulation in patients with Hashimoto’s hypothyroidism without increasing adverse event incidence.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

To explore the effect and mechanism of sodium propionate and mixed short-chain fatty acids on colitis induced by Citrobacter rodentium (C.r.) in mice. Mice were induced by oral gavage of C.r. The C.r. growth monitoring, histopathological analysis, qPCR analysis, intestinal permeability test and flow cytometry was used to study the effects of sodium propionate and mixed short-chain fatty acids on intestinal infection. The results showed that sodium propionate could inhibit the growth of C.r. more effectively than mixed short-chain fatty acids. Results of animal experiments showed that sodium propionate significantly reduced the weight loss and intestinal bacterial output in mice. Meanwhile, compared with mixed short chain fatty acids, sodium propionate effectively alleviated the pathological manifestations of colonic inflammatory infiltration, destruction of epithelial cell structure and decrease of goblet cell caused by C.r. infection, also increased the levels of antimicrobial peptides like interleukin-17 (IL-17) and regenerated islet derived protein 3γ (Reg3γ). In addition, sodium propionate decreased intestinal permeability better than mixed short-chain fatty acids, and sodium propionate significantly induced T helper cells 17 (Th17) and regulatory T cells (Treg) differentiation. The results showed that sodium propionate significantly alleviated colitis induced by C.r. infection compared with mixed short-chain fatty acids, which may be related to its inhibition of C.r. growth and enhancement of intestinal anti-infective function. The expected results can provide a safer and effective treatment strategy and scientific basis for colitis.

BACKGROUND:The pathogenesis of autoimmune hepatitis has not been clearly elucidated.Circular RNA(CircRNA)is a research hotspot in the field of RNA and is involved in the pathogenesis of many autoimmune diseases.However,the role of CircRNA in autoimmune hepatitis remains unclear. OBJECTIVE:To investigate the relationship between CircRNA(CircRNA)and concanavalin A induced liver injury in mice with autoimmune hepatitis. METHODS:Bioinformatics analysis was performed on CircRNA profiles selected by previous microarray technology,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,so as to explore the potential biological functions of these differentially expressed genes.Twelve C57BL/6 mice were randomized into normal group and model group(n=6 per group).Autoimmune hepatitis model was established by tail vein injection of concanavalin A in the model group.Mice were killed at 12 hours after modeling to extract mouse liver and peripheral blood.The expression levels of CircRNAs were verified by qRT-PCR.Serum alanine aminotransferase and aspartate aminotransferase levels were detected by colorimetric method.The levels of oxidative stress indexes malondialdehyde and nitric oxide in mouse liver were detected by microplate method.The correlation between oxidative stress level and liver injury index was analyzed. RESULTS AND CONCLUSION:The results of GO analysis showed that the target genes with up-regulated CircRNAs expression were mainly involved in the biological processes of SNARE complex assembly regulation(P=0.004),their molecular functions were mainly metal ion binding(P=0.000 29),and the cell components were mainly enriched in CORVET complex(P=0.075).The biological processes involved in the down-regulated circRNAs target genes were mainly"negative regulation of pancreatic secretion"(P=0.000 42),the molecular functions were mainly"transcriptional activator activity"(P=0.025),and the cell components were mainly enriched in"extracellular components"(P=0.006).KEGG results showed that the target genes with up-regulated CircRNAs expression were mainly enriched in the"base excision-repair"signaling pathways(P=0.026).Compared with the normal group,serum alanine aminotransferase and aspartate aminotransferase levels and the levels of malondialdehyde and nitric oxide in mouse liver in the model group were significantly increased(P＜0.01).Compared with the normal group,the expression of two selected CircRNAs(mmu-circ-0001520 and mmu-circ-0001577)was increased in the model group(P＜0.05).Spearman correlation analysis showed that the expression of mmu-circ-0001520 and mmu-circ-0001577 was positively correlated with alanine aminotransferase,aspartate aminotransferase,malondialdehyde and nitric oxide.To conclude,the differential expression of CircRNAs is correlated with liver injury in autoimmune hepatitis mice.mmu-circ-0001520 and mmu-circ-0001577 are expected to be diagnostic biomarkers and therapeutic targets for autoimmune hepatitis.

Objective:To construct an artificial intelligence (AI)-assisted system based on deep learning for corneal in vivo confocal microscopy (IVCM) image recognition and to evaluate its value in clinical applications. Methods:A diagnostic study was conducted.A total of 18 860 corneal images were collected from 331 subjects who underwent IVCM examination at Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University from May 2021 to September 2022.The collected images were used for model training and testing after being reviewed and classified by corneal experts.The model design included a low-quality image filtering model, a corneal image diagnosis model, and a 4-layer identification model for corneal epithelium, Bowman membrane, stroma, and endothelium, to initially determine normal and abnormal corneal images and corresponding corneal layers.A human-machine competition was conducted with another 360 database-independent IVCM images to compare the accuracy and time spent on image recognition by three senior ophthalmologists and the AI system.In addition, 8 trainees without IVCM training and with less than three years of clinical experience were selected to recognize the same 360 images without and with model assistance to analyze the effectiveness of model assistance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2021-K148).Results:The accuracy of this diagnostic model in screening high-quality images was 0.954.Its overall accuracy in identifying normal/abnormal corneal images was 0.916 and 0.896 in the internal and external test sets, respectively.Its accuracy reached 0.983, 0.925 in the internal test sets and 0.988, 0.929 in the external test sets in identifying corneal layers of normal and abnormal images, respectively.In the human-machine competition, the overall recognition accuracy of the model was 0.878, which was similar to the average accuracy of the three senior physicians and was approximately 300 times faster than the experts in recognition speed.Trainees assisted by the system achieved an accuracy of 0.816±0.043 in identifying corneal layers of normal and abnormal images, which was significantly higher than 0.669±0.061 without model assistance ( t=6.304, P<0.001). Conclusions:A deep learning-based assistant system for corneal IVCM image recognition is successfully constructed.This system can discriminate normal/abnormal corneal images and diagnose the corresponding corneal layer of the images, which can improve the efficiency of clinical diagnosis and assist doctors in training and learning.

Objective:To investigate the clinical value of multiparametric myocardial imaging using a dual-layer detector spectral CT in the non-invasive preoperative assessment of patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI).Methods:The clinical and imaging data of 90 patients who underwent coronary CT angiography (CCTA) with dual-layer spectral detector CT and invasive coronary angiography (ICA) within 30 days at the Affiliated Changshu Hospital of Nantong University from January 2021 to October 2022 were retrospectively analyzed. A total of 189 coronary arteries were included in the study cohort. The patients were divided into PCI ( n=44) and non-PCI groups ( n=46) according to whether they received PCI after evaluation with ICA. The diameter stenosis rate of the coronary arteries, myocardial iodine concentration (IC) and effective atomic number (Z eff) values were obtained from CCTA conventional and spectral images. The IC values and Z eff values of the myocardium in the areas with abnormal perfusion were compared with those in the areas with normal perfusion. The diagnostic performance of these parameters, as well as their combined model, was evaluated and compared using receiver operating characteristic (ROC) curve and area under the curve (AUC) in the pre-PCI assessment of patients with CHD. Results:Baseline patient data did not show statistically significant differences between the PCI and non-PCI groups (all P>0.05). There were statistically significant differences in IC values [(0.42±0.28) and (2.26±0.48) mg/ml] and Z eff values (7.39±0.33 and 8.50±0.25) between the myocardium areas with abnormal perfusion and the myocardium areas with normal perfusion in all patients (all P<0.001). The AUC for assessing whether patients with CHD need PCI treatment using myocardial IC and Z eff values were 0.865 and 0.853, respectively, which were significantly higher than assessment based only on lumen diameter stenosis rate (AUC=0.726, P<0.001). Conclusions:The IC and Z eff derived from myocardial spectral images can be used to diagnose myocardial perfusion abnormalities in patients with CHD. The spectral myocardial multi-parameters imaging shows promising potentials in pre-PCI assessment of patients with CHD, which can improve the efficiency of evaluation and may help to avoid unnecessarily invasive procedures.