ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Hereditary carotid body tumor (HCBT) is a rare neuroendocrine tumor mainly caused by germline mutations of the SDHx gene. Its multifocality, familial aggregation, and potential malignant risk pose unique challenges to diagnosis and treatment. This review systematically expounds the molecular mechanism of HCBT, pointing out that SDHx mutations drive tumorigenesis through the “pseudo-hypoxia” pathway and are regulated by epigenetic and somatic mutations. In terms of diagnosis, we emphasize the crucial role of ⁶⁸Ga-DOTATATE PET/CT and SDHB immunohistochemistry and advocate for multigene panel sequencing for patients with high-risk characteristics (such as early-onset, multifocal, family history or malignant signs) to clarify the genetic background. On the basis of existing evidence, we recommend conducting baseline biochemical tests for all newly diagnosed patients and actively suggest genetic screening for high-risk individuals such as those who are young, have multifocal tumors, or have a family history. In terms of treatment, surgery is the main treatment method for HCBT. Nevertheless, individualized strategies still need to be formulated based on tumor classification and patient’s overall condition and genetic background. Comprehensive management measures such as targeted therapy, radionuclide therapy, and standardized family management are crucial for improving the prognosis of patients.

ObjectiveTo investigate the effect of kynurenine-3-monooxygenase （KMO） on the function of fibroblast-like synoviocytes （FLS） in rheumatoid arthritis （RA）. MethodsKMO expression in synovial tissues from RA patients and healthy controls （HC） was analyzed using bioinformatics. Synovial tissues from RA patients and HC were collected， and KMO expression in FLS within synovial tissues was detected by immunofluorescence （IF）. In vitro experiments were performed using human rheumatoid arthritis fibroblast-like synoviocytes （MH7A）. Following KMO overexpression， KMO knockdown， and KMO inhibition with the specific inhibitor Ro61-8048 in MH7A cells， Western blot， CCK-8， EdU， Transwell and ELISA assays were used to evaluate alterations in cell viability， proliferation， migration and secretory function. ResultsBioinformatic analysis revealed significantly higher KMO gene expression in RA synovial tissue compared to the HC group （P<0.001）. IF results showed increased KMO expression in FLS from RA synovial tissues relative to the HC group （P<0.01）. Overexpression of KMO led to enhanced viability， proliferation， migration， and secretory capabilities of MH7A cells （all P<0.05）， whereas knockdown or inhibition of KMO with Ro61-8048 markedly suppressed these functions （all P<0.05）. ConclusionThe expression of KMO is upregulated in the synovial tissues of RA patients and promotes the activation of RA-FLS， suggesting that KMO may serve as a potential therapeutic target for RA treatment.

Spinal cord injury(SCI)can result in varying degrees of spinal motor dysfunction,partial sensory loss and sphincter dysfunction.SCI is divided into two stages:primary injury and secondary injury.The spinal cord cell necrosis during the primary injury period and apoptosis,oxidative stress and autophagy during the secondary injury period lead a large number of cell injury and permanant neurodysfunction.The histone deacetylase(HDAC)plays a key role in regulating the cellular viability and gene transcription.Neuro-dysfunction induced by SCI is associated with transcriptional dysfunction associated with unbalanced levels of protein acetylation.Valproic acid(VPA)is a inhibitor of HDAC and is usually used as an antiepileptic drug in clinic.Studies show that VPA may have the potential to treat the central nervous system diseases.VPA inhib-its HDAC,and then regulates oxidative stress,cellular autophagy,ion imbalance,microglia differentiation and inflammatory response,and plays the neuroprotective effect.This paper reviewed the related molecular mecha-nism of VPA in treating SCI.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

Objective:To explore the effects of the "group+individual" combined internet occupational health management model on the physiological indicators, pulmonary imaging changes and self-management ability of people with pneumoconiosis.Methods:In November 2022, patients diagnosed with pneumoconiosis in Baotou city from January 2012 to January 2022 were selected. Eighty cases exhibiting a decline in forcect expiratory volume in one second (FEV 1) and pulmonary imaging changes (primarily ground-glass opacity variations) were chosen as study subjects. These patients were randomly divided into a control group and an experimental group using the sealed envelope method, with 40 patients in each group. The control group received conventional outpatient follow-up and occupational health surveillance management, while the experimental group underwent a remote occupational health management model combining "group+individual" approaches over 12 months, with interventions administered once every 3 months. Comparative analysis was conducted on pre-and pos-management indicators between the two groups, including pulmonary function, pulmonary imaging changes, and self-management ability scores. Results:After occupational health management, the experimental group showed superior improvement in observed indicators (including pulmonary function and pulmonary imaging indicators) compared to the control group ( P<0.05). The self-management ability scores of the experimental group after occupational health management were also better than those of the control group (all P<0.05) . Conclusion:The remote occupational health management model combining group management and individualized guidance, when applied to patients with pneumoconiosis, is beneficial for improving their physiological indicators, pulmonary imaging indicators, and enhancing self-management abilities.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To investigate the current status of clinical leadership among Interventional Operating Room nurses in Shandong Province and to analyze its influencing factors.Methods:In December 2024, 220 Interventional Operating Room nurses from 46 ClassⅢ Grade A general hospitals in Shandong Province were selected for a cross-sectional survey using convenience sampling. General Information Questionnaire, Clinical Leadership Survey, Chinese version of Wong and Law Emotional Intelligence Scale (WLEIS-C) , and Jefferson Scale of Empathy-Health Professionals (JSE-HP) were used as survey instruments. Multiple linear regression was used to analyze the factors influencing clinical leadership among Interventional Operating Room nurses. Pearson correlation analysis was used to explore the relationship between emotional intelligence, empathy, and clinical leadership.Results:A total of 220 questionnaires were distributed and 204 valid questionnaires were recovered, with a valid recovery rate of 92.73% (204/220) . The clinical leadership scores of the 204 Interventional Operating Room nurses were (66.35±8.74) , and the dimensions scored, in descending order, as encouraging the heart, enabling others to act, modeling the way, inspiring a shared vision, and challenging the process. The mean scores of WLEIS-C and JSE-HP items were (5.88±0.90) and (4.61±0.63) , respectively. Multiple linear regression analysis showed that the nature of employment and whether or not they participated in leadership training were influencing factors for clinical leadership among Interventional Operating Room nurses (partial regression coefficients of -2.831 and -2.999, respectively; P<0.05) . Emotional intelligence and empathy ability among Interventional Operating Room nurses were positively correlated with clinical leadership ( P<0.05) . Conclusions:Clinical leadership of nurses in the Interventional Operating Room of ClassⅢ Grade A general hospitals in Shandong Province is at a moderate to high level. Nurses who participate in leadership training, have staffing, have greater empathy, and have higher emotional intelligence have greater clinical leadership. It is recommended that nursing administrators add leadership-related courses to the training of nurses in the Interventional Operating Room, and take steps to improve nurses' emotional intelligence and empathy ability, thereby promoting clinical leadership among Interventional Operating Room nurses.