BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: To investigate correlation between preoperative C ₂ slope (C2S) and effectiveness at 2 years after short-segment anterior cervical discectomy and fusion (ACDF), with the aim of providing reliable indicators for predicting effectiveness. METHODS: One hundred and eighteen patients with cervical spondylotic myelopathy, who received short-segment ACDF between January 2018 and December 2022 and met the selection criteria, were enrolled in the study. There were 46 males and 72 females, aged from 26 to 80 years, with a mean age of 53.6 years. The operative duration was (127.6±33.46) minutes and the intraoperative blood loss was (34.75±30.40) mL. All patients were followed up 2 years. The pre- and post-operative Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score for pain were recorded. Based on the anteroposterior and lateral cervical X-ray films, the sagittal parameters of the cervical spine were measured [C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, T ₁ slope, C2S, sagittal segmental angle (SSA) of the surgical segment, and average surgical disc height (ASDH) of the surgical segment]. Statistical analyses were performed to assess the differences in these indicators between pre- and post-operation, as well as the correlations between the preoperative C2S and the JOA score, NDI, and VAS score at 2 years after operation. The patients were allocated into group A (C2S >11.73°) and group B (C2S≤ 11.73°) according to the median value of the preoperative C2S (11.73°). The JOA score, NDI, and VAS score before operation and at 2 years after operation, as well as the differences between pre- and post-operative values (change values), were compared between the two groups. RESULTS: The T ₁ slope, C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, SSA, and ASDH at immediate after operation and JOA score, NDI, and VAS score at 2 years after operation significantly improved in 118 patients when compared with preoperative ones ( P<0.05). Pearson correlation analysis showed that preoperative C2S was not correlated with JOA score and NDI at 2 years after operation ( P>0.05), but negatively correlated with VAS score ( P<0.05). There were 59 patients with preoperative C2S>11.73° (group A) and 59 with C2S≤11.73° (group B). There was no significant difference in preoperative JOA score, NDI, and VAS score between the two groups ( P>0.05). There were significant differences in VAS score at 2 year after operation and the change value between the two groups ( P<0.05); there was no significant difference in the JOA score and NDI ( P>0.05). CONCLUSION Patients with cervical spondylotic myelopathy and a higher preoperative C2S exhibited superior long-term pain relief and effectiveness following short-segment ACDF.
Humans ; Male ; Spinal Fusion/methods* ; Female ; Middle Aged ; Cervical Vertebrae/diagnostic imaging* ; Diskectomy/methods* ; Aged ; Adult ; Treatment Outcome ; Aged, 80 and over ; Spondylosis/diagnostic imaging* ; Pain Measurement ; Preoperative Period ; Follow-Up Studies

OBJECTIVE: To investigate the relationship between peripheral blood T-cell immunoglobulin mucin-3 (TIM-3) and iron overload in patients with myelodysplastic syndrome (MDS) undergoing red blood cell transfusion. METHODS: 120 MDS patients who received treatment at Wuhan Third Hospital from June 2020 to May 2022 were included and analyzed as research subjects, all of whom met the indications for red blood cell transfusion. Blood routine and biochemical indicators were tested before transfusion, and general clinical data of the patients were statistically analyzed. The iron metabolism status of the patients were evaluated. The clinical characteristics of patients with iron overload and the factors affecting iron overload were analyzed. And a correlation analysis was conducted between TIM-3 and other factors affecting iron overload. RESULTS: Among the 120 MDS patients included in this study, 82 cases (68.33%) were detected to have iron overload after red blood cell transfusion. The occurrence time of iron overload was 20-42 weeks, with an average time of 32.35±5.26 weeks, calculated from the first transfusion of red blood cells. The proportion of patients with high-risk and extremely high-risk according to the revised International Prognostic Scoring System (IPSS-R) and WHO classification-based Prognostic Scoring System (WPSS), the volume of blood transfusions, the proportion of transfusion-dependent patients, and the levels of serum hepcidin (Hepc), erythropoietin (EPO), and TIM-3 in patients with iron overload were higher than those in patients with normal iron metabolism, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high-risk and extremely high-risk according to WPSS, blood transfusion volume, transfusion dependence, and upregulation of serum Hepc, EPO, and TIM-3 expression were factors affecting iron overload in MDS patients undergoing red blood cell transfusion (P < 0.05). Pearson correlation analysis showed that serum TIM-3 level in MDS patients were positively correlated with the other factors affecting iron overload (P < 0.05). CONCLUSION Serum TIM-3 is associated with iron overload in MDS patients undergoing red blood cell transfusion, and upregulation of serum TIM-3 expression increases the risk of iron overload after red blood cell transfusion.
Humans ; Myelodysplastic Syndromes/blood* ; Iron Overload/blood* ; Hepatitis A Virus Cellular Receptor 2/blood* ; Erythrocyte Transfusion ; Male ; Female ; Middle Aged ; Aged ; Iron

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Technological innovation and management transformation not only introduce negentropy into public hospital organizations but may also exacerbate entropy accumulation.Different combinations of diagnostic and treatment technologies and management transformations have different impacts on the total entropy.While improved diagnostic-therapeutic technologies and management transformations enhance technological negentropy and managerial negentropy,thereby increasing operational efficiency,it may simultaneously increases organizational complexity,causing inefficient information flow,delayed decision-making,resource wastage,and elevated technological entropy and managerial entropy.Specialty-driven deployment of hospital management strategies enables a dual-driven mechanism to introduce negentropy.By constructing dissipative structures that enhance"synergistic negentropy"while reducing"internal friction entropy",hospitals can decrease organizational disorder and increase diagnostic-therapeutic coordination to achieve high-quality development.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

Patients with lacunar infarction (LI) have a higher risk of stroke recurrence compared to other types of stroke, and it is an important pathological basis for vascular dementia. Homocysteine (Hcy) is closely associated with the occurrence and development of LI. The mechanism by which Hcy causes LI involves multiple complex biological processes (including inflammation, oxidative stress, endothelial dysfunction, etc.) and synergistic effects with various risk factors (such as hypertension and hyperglycemia), but the specific mechanism is currently not fully elucidated.