As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Hepatocellular carcinoma （HCC） with biliary duct tumor thrombus （BDTT） is currently not common in clinical practice and is easily misdiagnosed， and previously， it was often considered an advanced stage of the disease with a poor prognosis， making its treatment challenging. However， in-depth studies in recent years have gradually deepened our understanding of this disease， leading to significant changes in diagnostic and treatment concepts. Currently， comprehensive treatment， mainly surgery， is used for treatment， but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis， in order to provide a reference for clinical treatment options.

Objective:To investigate the efficacy and safety of endovascular treatment (EVT) in young patients with symptomatic intracranial atherosclerotic stenosis (sICAS).Methods:Young patients with sICAS admitted to the Department of Neurology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University, Medical School from January 2020 to July 2024 were included retrospectively. According to the therapeutic modalities, they were divided into a best medical treatment (BMT) group and an EVT group. The efficacy outcome was any stroke recurrence or death within 30 days and 1 year. The safety outcome was symptomatic intracranial hemorrhage (sICH) within 30 days and restenosis within 1 year.Results:A total of 113 patients were enrolled, including 85 males (75.2%), with a median age of 43 (interquartile range, 37-48) years; 44 patients (38.9%) received EVT, and 69 (61.1%) received BMT. Among the 44 patients who underwent EVT, 8 (18.2%) underwent balloon angioplasty and 36 (81.8%) underwent stenting. There was no significant difference in the incidence of stroke recurrence or death within 30 days (2.9% vs. 2.3%) and sICH incidence (0% vs. 2.3%) between the BMT group and the EVT group. However, the 1-year stroke recurrence or death rate in the EVT group was significantly lower than that in the BMT group (18.8% vs. 4.5%; P=0.029). Cox proportional hazards regression analysis showed that EVT was independently associated with a lower incidence of stroke recurrence or death within 1 year (hazard ratio 0.225, 95% confidence interval 0.051-0.996; P<0.05). The median age of the balloon angioplasty group was significantly lower than that of the stenting group (33.5 years vs. 46 years; P=0.007), while there were no significant differences in other demographic and baseline data. There was no significant difference in all efficacy and safety outcome between the balloon angioplasty group and the stenting group. Conclusions:For young patients with sICAS who have an unsatisfactory response to drug treatment, EVT can reduce the risk of stroke recurrence or death within 1 year without increasing the risk of sICH. The safety and efficacy of balloon angioplasty and stenting are similar.

Objective To investigate the distribution of gender,age,and traditional Chinese medicine(TCM)syndrome elements and syndrome types in patients suffering from novel coronavirus infection complicated with asthma,and to explore the medication rules for the patients,thus to provide reference for the formulation of clinical diagnosis and treatment plans for novel coronavirus infection complicated with asthma.Methods From December 2022 to January 2023,the information of gender,age,syndrome elements,TCM syndrome types and medication frequency of the herbal medicine was collected among the patients suffering from novel coronavirus infection complicated with asthma who were treated in outpatient clinics of the respiratory department and emergency department of Shenzhen Traditional Chinese Medicine Hospital.The information data were statistically analyzed and then the network visualization of results was presented.Results A total of 63 cases were included,including 27 males and 36 females,with an average age of 51.8 years old.Thirteen TCM syndrome types were involved,of which the three with the leading occurrence frequency were wind-phlegm syndrome(17 cases),spleen deficiency with dampness accumulation syndrome(11 cases),and phlegm-heat stagnation in the lung syndrome(8 cases).There were four disease-location syndrome elements,and the top two were lung(36 cases)and spleen(12 cases).Eight disease-nature syndrome elements were involved,and the top three were wind(36 cases),phlegm(28 cases)and qi deficiency(24 cases).A total of 128 Chinese herbal medicines were used,and their properties and flavors were predomiated by being pungent,bitter,sweet and cold.Most of the Chinese herbal medicines had the meridian tropism of lung,spleen,liver and stomach meridians,and most of the Chinese herbal medicines had the therapeutic actions of resolving phlegm,easing cough and relieving asthma.The top four Chinese herbal medicines with higher medication frequency were Glycyrrhizae Radix et Rhizoma(51 times),Ephedrae Herba(47 times),blanching Armeniacae Semen Amarum(44 times),and Schisandrae Chinensis Fructus(40 times).The core two-drug groups were Ephedrae Herba-Glycyrrhizae Radix et Rhizoma,Ephedrae Herba-Schisandrae Chinensis Fructus,and blanching Armeniacae Semen Amarum-Pinelliae Rhizoma.The core three-drug groups were Pinelliae Rhizoma-blanching Armeniacae Semen Amarum-Ephedrae Herba,and Ephedrae Herba-Schisandrae Chinensis Fructus-Glycyrrhizae Radix et Rhizoma.Conclusion Pathogenic phlegm retention in lung is the core pathogenesis of novel coronavirus infection complicated with asthma,which is protracted through the disease.The pathogenic wind is the driving factor of the disease's development and progression,and in the middle and late stages of the disease,the complicated syndrome manifestations of pathogenic heat,qi deficiency,qi and yin deficiency,and blockage of upper orifice are commonly seen.Its therapeutic principles are to relieve exterior syndrome and clear heat,resolve phlegm,ease cough and relieve asthma,thus to restore the qi movement of the zang-fu organs,support the healthy qi,eliminate pathogens and strengthen body resistance.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndrome patterns and medication characteristics in corona virus disease 2019(COVID-19)patients complicated with chronic bronchitis at the initial phase of the termination of pandemic control policy in Shenzhen,and to provide evidence for TCM syndrome differentiation and treatment of these patients.Methods A retrospective analysis was performed on 76 COVID-19 patients complicated with chronic bronchitis who visited the Department of Respiratory and Critical Care Medicine or the Emergency Internal Medicine Clinic at Shenzhen Traditional Chinese Medicine Hospital between December 15,2022 and February 28,2023,an initial phase of the termination of pandemic control policy in Shenzhen.Data of demographics,TCM syndrome patterns,and herbal prescriptions were collected.TCM syndrome distribution and medication patterns of the COVID-19 patients complicated with chronic bronchitis were summarized to enhance understanding of post-COVID sequelae,post-COVID syndrome,long COVID,post-infectious cough,and chronic cough,and to provide references for TCM management of acute/chronic post-COVID cough,long COVID syndrome,and emerging respiratory infectious diseases.Results A total of 76 medical records with full information were included,covering 63 herbal formulas and 140 herbal medicinals were analyzed.The most common TCM syndrome pattern was phlegm-turbidity obstructing the lung syndrome,followed by phlegm-heat stagnating the lung syndrome and lung qi deficiency syndrome.The properties of the herbs used were predominantly warm,cold,or mild;their flavors were bitter,pungent,or sweet;and their meridian tropisms primarily involved the lung,spleen,stomach,and liver.Twenty-five medicinals used exceeding 15 times in the formulas were identified,including Glycyrrhizae Radix et Rhizoma(Gancao),Ephedrae Herba(Mahuang),Coicis Semen(Yiyiren),and Poira(Fuling).Association rule analysis revealed the frequent herbal pairs of Gancao-Mahuang,Belamcandae Rhizoma(Shegan)-Mahuang,Gancao-Fuling,Fuling-Yiyiren,etc.Cluster analysis categorized high-frequency herbs into four distinct groups.Conclusion The retrospective analysis highlights the complexity of clinical manifestations in COVID-19 patients complicated with chronic bronchitis at the initial phase of the termination of pandemic control policy in Shenzhen.The pathogenic factors of the patients predominantly involve phlegm-turbidity and phlegm-heat.Therapeutic principles for the patients focus on diffusing the lung to alleviate adverse flow of qi,resolving phlegm and removing dampness,and clearing and draining damp-heat.Commonly prescribed formulas include San'ao Decoction,Yuebi Plus Banxia Decoction,Xiaoqinglong Decoction,Shegan Mahuang Decoction,and Suhuang Zhike Decoction,and the formulas are used by modification according to the symptoms.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Rheumatoid arthritis (RA) represents a persistent autoimmune condition distinguished by a multifaceted etiology that encompasses both genetic and environmental factors. Recent progress in understanding the mechanisms behind RA pathogenesis has delved into the critical role of epigenetic regulatory processes, including DNA methylation, histone modifications, and the regulation by microRNAs (miRNAs). These findings provide new insights into the intricate nature of RA and pave the way for innovative therapeutic strategies. This review consolidates the latest developments in the epigenetic regulation of RA, concentrating on how these mechanisms affect the dysregulated signaling pathways associated with the disease. We analyze the roles of specific proteins that function as 'writers', 'erasers', and 'readers' in epigenetic modifications, highlighting their potential as targets for therapeutic intervention. Additionally, in view of the significance of miRNAs in the pathogenesis of RA, we deliberate on their involvement in disease progression and explore miRNA-based treatment strategies. By integrating these diverse epigenetic dimensions, this review offers a comprehensive epigenetic perspective on RA pathogenesis and identifies promising avenues for future research and therapeutic interventions.

Objective: To explore the alleviating effect of geniposide on ulcerative colitis (UC) and to investigate its potential mechanism. Methods: A UC mouse model was induced using 5% dextran sulfate sodium ( DSS) . These mice were randomly divided into 6 groups ( n = 8) : control group , model group , sulfasalazine group[ 100 mg/(kg ·d) ] , low-dose geniposide group[ 10 mg/(kg ·d) ] , medium-dose geniposide group[20 mg/(kg ·d) ] , and high-dose geniposide group[40 mg/( kg · d) ] . The mice were orally administered for consecutive 10 days . The colon length and mouse body mass were measured , and the colon mucosal damage index (CMDI) and disease activity index (DAI) were scored . The pathological changes in colon tissue were observed using hematoxylin-eosin (HE) staining. The reagent kits were used to measure the levels of malondialdehyde ( MDA) , myeloperoxidase (MPO) , catalase ( CAT) , and glutathione ( GSH) in colon tissue . The enzyme linked immunosorbent assay (ELISA) was used to analyze the expression levels of tumor necrosis factor-α ( TNF-α) , interleukin-6 ( IL-6) , and IL-1βin colon tissue . Western blot was used to detect the protein expression of mucin 1 (MUC-1) , occludin , IL-6 , p-JAK2 , and p-STAT3 in colon tissue . Results: Compared with the normal control group , the body mass and colon length of the model group mice significantly reduced . The expression of MUC-1 and occludin proteins sig- nificantly reduced (P < 0. 01) . The activities of CAT and SOD significantly reduced . DAI score and CMDI score significantly increased (P < 0. 01) . The expression levels of TNF-α, IL-6 , and IL-1βsignificantly increased (P < 0. 01) . The content of MPO and MDA significantly increased (P < 0. 01) . The expression of IL-6 , p-JAK2 and p- STAT3 proteins significantly increased ( P < 0. 01) . Compared with the model group , the body mass and colon length of mice in sulfasalazine group and geniposide medium and high-dose groups significantly increased (P < 0. 05 or P < 0. 01) , the expression of MUC-1 and occludin proteins increased (P < 0. 05 or P < 0. 01) , as well as the activity of CAT and SOD (P < 0. 05 or P < 0. 01) . DAI score and CMDI score in Sulfasalazine group and genipo- side medium and high-dose groups significantly reduced (P < 0. 05 or P < 0. 01) , as well as the expression levels of TNF-α, IL-6 , and IL-1β(P < 0. 05 or P < 0. 01) . MPO and MDA content in Sulfasalazine group and genipo- side medium and high-dose groups significantly reduced (P < 0. 05 or P < 0. 01) , as well as the expression of IL- 6 , p-JAK2 , and p-STAT3 proteins (P < 0. 05 or P < 0. 01) . Conclusion Geniposide maintaines intestinal home- ostasis by regulating the structure of the intestinal flora and improves colitis injury in UC mice by inhibiting the acti- vation of the IL-6/JAK2/STAT3 pathway.

Xenotransplantation is one of the effective ways to overcome the shortage of donor organs. However, the molecular incompatibility between xenotransplantation donors and recipients can cause rejection, which greatly limits the clinical application of xenotransplantation. In recent years, researchers have deeply explored the mechanism of xenotransplantation rejection through xenotransplantation models of pig-to-monkey and pig-to-brain death recipients, and found that the innate immune system plays an important role in rejection. Macrophages, as phagocytes in the innate immune system, not only damage xenografts through phagocytosis but also interact with other immune cells to influence the immune microenvironment of xenotransplantation. However, due to the heterogeneity of macrophages, their phenotypes and functions in xenotransplantation rejection remain unclear. Therefore, it is necessary to further explore the role of macrophages in xenotransplantation rejection. This article reviews the latest research progress of macrophages in xenotransplantation rejection, aiming to explore the mechanisms of macrophages in xenotransplantation rejection and provide references for future research.