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.

ObjectiveTo investigate the differential expression of integrin alpha-6（ITGA6） in abdominal wall endometriosis （AWE） tissues and its molecular mechanisms in regulating AWE. Methods36 AWE lesions were designated as the experimental group， while 36 cases of normal endometrial tissues served as the controls. Differential expression of ITGA6 between the two groups was assessed through immunohistochemical （IHC） staining. Human ITGA6 gene-specific interference sequences were designed， synthesized， and packaged into lentiviral vectors to establish the Ishikawa cell line with ITGA6-knockdown. Similarly， the ITGA6-overexpression cell line was constructed using the coding sequence （CDS） of the gene. Real-time PCR and Western blot were performed to detect changes in epithelial-mesenchymal transition（EMT）-related markers and angiogenesis-related indicators. Cell invasion and migration capabilities were assessed by Cell Scratch and Transwell assays. Furthermore， Western blot was conducted to profile PI3K/AKT pathway dynamics. ResultsEctopic endometrial tissues exhibited a marked increase in the number of ITGA6-positive cells and their expression intensity compared to eutopic endometrium （each P < 0.001）. Compared with the NC group， the ITGA6-knockdown group showed significantly reduced expression of N-cadherin， VEGF， and TGF-β1 （all P < 0.01）， while E-cadherin expression was markedly increased （P < 0.01）. Concomitantly， the invasion and migration capacities of ITGA6-low expression were significantly impaired （P < 0.001 for both）， accompanied by a marked reduction in AKT and phosphorylated AKT（p-AKT） levels （P < 0.001）. Conversely， overexpressing ITGA6 resulted in opposite effects. ConclusionITGA6 modulates EMT and angiogenesis in Ishikawa cells via the PI3K/AKT signaling pathway， thereby enhancing cell invasion and migration capabilities， which contributes to the pathogenesis of AWE.

Objective To explore the imaging characteristics of lung cancers associated with cystic airspaces (LCCA) and the effects of different treatment regimens. Methods A retrospective analysis was conducted on the clinical and radiological data of LCCA patients who underwent surgical resection and pathological confirmation at the Department of Thoracic Surgery, the First Affiliated Hospital of Soochow University from 2016 to 2023. The relationship between various radiological classifications and clinical pathology was studied. Based on the postoperative adjuvant treatment follow-up results, the effects of different treatment regimens were analyzed. Results A total of 147 patients were included, including 90 males and 57 females, with a median age of 63 (55, 70) years. There were 21 patients of imaging typeⅠ, 50 patients of typeⅡ, 57 patients of type Ⅲ, and 19 patients of type Ⅳ. The lobulation sign or burr sign of typeⅠcyst walls (P=0.004), and intracystic septa (P=0.030) were more commonly seen in the high-aggressiveness group. The components of the cyst walls or nodules of types Ⅰ-Ⅳ in the high-aggressiveness group were mostly solid or sub-solid (P<0.05). Multivariate logistic regression analysis indicated that subsolid cyst wall (OR=4.734, P=0.023), solid cyst wall (OR=97.972, P<0.001), and the lobulation sign or burr sign of the cyst wall (OR=13.215, P=0.024) were independent risk factors for aggressiveness. Fifty-eight patients received adjuvant therapy after surgery, including 22 in the chemotherapy group, 15 in the targeted therapy group, and 21 in the combined therapy group. The progression-free survival of the combined therapy group was better than the other two groups (P=0.045). Conclusion There is a correlation between the imaging features of LCCA and pathological aggressiveness. Compared to postoperative targeted therapy or chemotherapy alone, postoperative chemotherapy combined with targeted therapy can improve the progression-free survival of LCCA patients.

Congenital blood group chimerism refers to the coexistence of two or more distinct blood types within an individual, resulting from the presence of hematopoietic cell populations with different genotypes. Consequently, red blood cells in such individuals may express different blood group antigens. Based on the timing and mechanism of formation, blood group chimerism can be classified as either congenital or acquired. Although congenital blood group chimerism is rare and involves complex mechanisms, it holds significant implications in transfusion medicine, transplantation, and obstetrics. This article reviews the formation mechanisms, detection methods, and clinical significance of congenital blood group chimerism in transfusion medicine. Particular emphasis is placed on the principles, advantages, and limitations of various detection techniques. Furthermore, the potential applications of these technologies in clinical diagnosis are discussed, providing a technical foundation for the development of precise transfusion strategies.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

This article explores the construction and practice of the"Party Building+Health Science Popularization"model,using the"Yixian Health Science Popularization Guangdong Tour"campaign conducted by Sun Yat-sen Memorial Hospital as a case study.The initiative has achieved remarkable results.Additionally,it summarizes innovative measures,as well as uni-versal and exemplary experiences,providing new insights and pathway recommendations for public hospitals to develop the"Party Building+Health Science Popularization"model.

Objective To investigate the molecular mechanism by which salidroside inhibits the proliferation of gastric cancer(GC)cells through upregulation of miR-1343-3p.Methods RNA databases were used to screen for mRNAs associated with tumor proliferation and with miR-1343-3p,and exhibiting significant changes in their expression levels after salidroside treatment of human GC cells.Gene matching and immunoprecipitation of RNA-binding proteins were conducted to analyze the association between miR-1343-3p and SOX18.Immunocytochemistry was performed to determine the localization of SOX18 protein.The effect of salidroside on the proliferation of human GC cells(MGC-803 and AGS)was determined by CCK-8 assay.Human GC cells were divided into a blank control group and low-and high-dose salidroside groups.The expression of miR-1343-3p and SOX18 mRNA was measured by real-time quantitative fluorescence PCR(qPCR).The protein expression of SOX18 was measured by Western blot.GC cells were co-transfected with miR-1343-3p mimic and miR-1343-3p inhibitor,respectively,via LipofectamineTM 2000 liposomes.The expression of miR-1343-3p and SOX18 mRNA was measured by qPCR,and the protein expression of SOX18 was measured by Western blot.Results Through bioinformatic analysis,SOX18 was identified as a downstream target of miR-1343-3p.Gene alignment confirmed the presence of specific binding sites between the two genes,and immunoprecipitation of RNA-binding proteins validated the targeting relationship between them(P<0.05).Immunocytochemistry demonstrated the nuclear localization of SOX18 protein.CCK-8 assay findings demonstrated that salidroside significantly inhibited the proliferation of GC cells in a time-and dose-dependent manner.Compared with the blank control group,salidroside-treated GC cells showed decreased expression of both SOX18 mRNA and protein(P<0.05)and an increased miR-1343-3p expression(P<0.05).Compared with the control group,GC cells in the miR-1343-3p mimic group exhibited increased expression of miR-1343-3p and decreased expression of SOX18 mRNA and protein.In contrast,GC cells in the miR-1343-3p inhibitor group showed decreased expression of miR-1343-3p and increased expression of SOX18 mRNA and protein(all P<0.05).Conclusion Salidroside may inhibit the proliferation of GC cells by regulating the miR-1343-3p/SOX18 signaling axis and these regulators may present new potential therapeutic targets or biomarkers for gastric cancer.