ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

Objective To explore the application value of fractional anisotropy(FA)analysis of RGB component transformation in different directions of fibers in substantia nigra in Parkinson's disease(PD).Methods There were 35 cases of PD and 37 cases of normal control group.After being performed by brain diffusion tensor imaging(DTI)scanning,the sequence was imported into 3DSlicense 5.6.0,and the diffusion module was used to implement pseudo color mapping based on FA,locate and segment substantia nigra,and use the substantia nigra mask as the tracking starting point.After forming tracing,fibers were imported into DTIANALYSIS 1.51,converting the RGB components into FA values for analysis,and visualized the analysis result.At the same time,fiber length,fiber density,and segmented FA point cloud percentage were compared.Results Compared with the normal group,the length of substantia nigra fibers in the PD group was shorter[(95.14±19.85)mm vs(115.99±21.39)mm,P＜0.01],and there was a statistical difference between the two groups.There was no statistical difference in fiber density[(0.07±0.05)/mm3 vs(0.10±0.12)/mm3,P＞0.05]between control group and PD group.The percentage of FA segment point clouds in the PD group was lower than that in the normal group at 0.9-1,but the principal component characteristics of the point cloud ratios in each FA segment were not significant.Conclusion Based on the transformation of RGB components into FA analysis,the length,density,and FA values of substantia nigra nerve fibers in PD patients can be quantified and visualized,providing a basis for the study of PD neural pathways.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.