ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules （composed of Lonicerae Japonicae Flos， Sedi Herba， Paeoniae Radix Rubra， Moutan Cortex， Rhei Radix et Rhizoma Praeparata， and Glycyrrhizae Radix et Rhizoma） combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis （ST） of lower extremities， and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized， double-blind， placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups（62 cases in each group）. The control group received external application of Jinhuang ointment and oral placebo treatment， while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores， therapeutic efficacy of traditional Chinese medicine （TCM） syndrome， pain visual analog scale （VAS） scores， hemorheological indices ［including whole blood high-shear， medium-shear， and low-shear viscosity， as well as plasma viscosity （PV）］， and inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）］ were compared before and after treatment. ResultsAfter 2 weeks of treatment， the total effective rate in the observation group （98.3%， 60/62） was significantly higher than that in the control group （83.8%， 52/62）， with a statistically significant difference （Z=3.512 1， P<0.05）. Compared with pre-treatment scores， the scores for skin color， skin temperature， swelling， pain， and cord or nodules were significantly reduced in both groups （P<0.05）， with more pronounced improvement in the observation group （P<0.05）. Additionally， compared with pre-treatment levels， the whole blood viscosity （low-， medium-， and high-shear） significantly improved in both groups after treatment （P<0.05）， with more marked improvement in the observation group （P<0.05）. Furthermore， the plasma viscosity， CRP， IL-6， and TNF-α levels were significantly reduced in both groups after treatment （P<0.05）， with more pronounced improvement observed in the observation group （P<0.05）. ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms， hemorheological abnormalities， and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.

Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Endoscopic full-thickness resection (EFTR) is a minimally invasive technique that is increasingly used for gastrointestinal stromal tumors (GISTs) originating from the muscularis propria. Despite its advantages over conventional surgery, such as complete tumor resection and faster recovery, EFTR faces challenges related to its efficacy, safety, and feasibility, particularly in gastric GISTs. By summarizing the literature published over the past decade, this review provides a comprehensive overview of the clinical outcomes of EFTR and the evolution of defect closure devices.

The functional realization of proteins and other biological macromolecules depends on conformational dynamics and allosteric regulation, and elucidating their molecular mechanisms is an important foundation for understanding life processes. Molecular dynamics simulations are a powerful tool for investigating conformational evolution at the atomic level. However, traditional methods are limited by simulation timescales and high free-energy barriers, making it difficult to effectively capture rare conformations and their transition pathways. As a result, the development of enhanced sampling techniques has become key to overcoming this bottleneck. As a classical enhanced sampling technique, metadynamics suffers from several shortcomings, including strong dependence on collective variables and significant errors caused by bias potential accumulation. This article reviews three major improvement strategies. The first combines stochastic resetting with metadynamics, using trajectory-resetting mechanisms to improve sampling efficiency while avoiding the difficulty of optimizing collective variables. The second, SinkMeta, employs a “sinking” bias effect to enable efficient exploration of specific regions and paths. The third, OPES-based hybrid methods, improve the stability of free-energy estimation by optimizing the target distribution or the way the bias is constructed. These methods provide new ideas for characterizing free-energy landscapes and studying conformational transitions in complex biological systems, while also promoting the continued development of enhanced sampling methodologies.

Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

Objective: To optimize the technology and process for recovering immune cells from discarded leukocyte filter through reverse flushing, and to investigate the effects of different reverse flushing solutions and physical conditions (temperature, soaking, and ultrasound) on the cell recovery rate. Additionally, to evaluate the feasibility and quality of isolating and culturing NK cells from the recovered cells. Methods: Normal saline, PBS, and PBS-EDTA were used as reverse flushing solutions to backwash the filter, and the white blood cell recovery rates were compared. The reverse flushing efficiency was optimized by adjusting the temperature of the reverse flushing solution, filter soaking treatment and ultrasonic treatment. The Ficoll separation method was employed to isolate peripheral blood mononuclear cells (PBMCs) from the elution solution and conduct in vitro expansion and culture. Lymphocyte subsets were identified and quantified using flow cytometry. Results: The physiological saline served as the backflush fluid was the most stable. The reverse temperature had a significant impact on the recovery rate of white blood cell subgroups. The recovery rates of lymphocytes and monocytes at 37℃ were significantly higher than those at 4℃ [(35.56±5.55)% vs (22.88±0.31)%, (32.42±4.82)% vs (8.00±1.6)%, t=5.581 and 5.758, respectively, both P<0.001)], and at 25℃ [(35.56±5.55)% vs (22.42±6.13)%, t=5.904, P<0.001; (32.4±4.82)% vs (21.11±1.23)%, t=2.629, P=0.030)]. The recovery rates of white blood cell subgroups after 37℃ immersion were higher than those after direct reverse flow at 37℃, but the difference was not statistically significant (P>0.05). The recovery rate of cells after ultrasonic immersion at 25℃ was further increased compared to that after immersion at 25℃, but the difference was not statistically significant (P>0.05). The purity of the NK cells obtained through sorting reached (94.2±4.5)%, and the viability was (94.8±0.9)%. After 15 days of culture, the cell count was expanded approximately 450 times, yielding more than 10 /mL highly active NK cells. Conclusion: By optimizing the backflushing process, immune cells can be efficiently recovered from discarded filters. The 37℃ backflow liquid has the best backflow effect; soaking and ultrasonic treatment can be used as auxiliary methods to improve recovery rates. The NK cells from this source have high purity, good activity, and strong expansion ability, and can be used as a reliable cell source for immunotherapy research, and in line with the circular economy concept of resource reuse.

Objective To study the relationship of serum 25-hydroxyvitamin D3[25-(OH)D3],myostatin(MSTN),limb skeletal muscle index(ASMI)with osteopenia(OP)in patients with rheumatoid arthritis(RA)complicated with sarcopenia(SA).Methods A total of 244 RA patients selected as case group,and 123 healthy people who underwent physical examination in our hospital during the same period were selected as control group.The general data,serum levels of 25-(OH)D3,MSTN,ASMI and peripheral blood immune cells were compared among the two groups.The diagnostic value of serum 25-(OH)D3,MSTN and ASMI in RA patients with SA complicated with OP and the correlation between serum 25-(OH)D3,MSTN,ASMI and peripheral blood immune cells were analyzed.Results The levels of serum 25-(OH)D3,peripheral blood regulatory T lymphocyte(Treg)cells and ASMI in the case group were lower than those in the control group,while the levels of serum MSTN,peripheral blood helper T lymphocyte 17(Th17)cells and Th17/Treg were higher than those in the control group(P＜0.05).Among the 244 RA patients,171 had no SA,73 had SA,and the incidence of SA was 29.92％.The levels of serum 25-(OH)D3,peripheral blood Treg cells and ASMI in the SA group were lower than those in the non-SA group,and the levels of serum MSTN,peripheral blood Th17 cells and Th17/Treg were higher than those in the non-SA group(P＜0.05).The levels of serum 25-(OH)D3,peripheral blood Treg cells and ASMI in the OP group were lower than those in the non-OP group,while the levels of serum MSTN,peripheral blood Th17 cells and Th17/Treg were higher than those in the non-OP group(P＜0.05).The area under the curve(AUC)of combined detection of serum 25-(OH)D3,MSTN and ASMI for the diagnosis of OP in RA patients with SA was higher than that of the three alone(P＜0.05).Serum 25-(OH)D3 and ASMI in RA patients with SA complicated with or without OP were negatively correlated with peripheral blood Th17 cell level and Th17/Treg(P＜0.05),and positively correlated with peripheral blood Treg cell level(P＜0.05).The level of serum MSTN was positively correlated with the level of Th17 cells and Th17/Treg in peripheral blood(P＜0.05),and negatively correlated with the level of Treg cells in peripheral blood(P＜0.05).Conclusion The incidence of OP in RA patients with SA is high.At the same time,the occurrence of SA and OP can lead to the decrease of serum 25-(OH)D3,peripheral blood Th17 cell,Th17/Treg and ASMI,and the increase of serum MSTN and peripheral blood Treg cell.The combination detection of 25-(OH)D3,MSTN and ASMI can effectively improve the diagnosis of OP in RA patients with SA,and the levels of the three are significantly correlated with peripheral blood Th17 cells,Treg cells and Th17/Treg.

BACKGROUND:Microplastics are a common environmental pollutant that can cause damage to the gastrointestinal tract,liver and kidney,and reproductive system.However,little is known about the effects of microplastics on the prostate.OBJECTIVE:To investigate the effects of different charge-modified polystyrene microplastics on prostate tissues of male mice and its mechanism.METHODS:A total of 48 male BALB/c mice were randomly divided into a control group,an unmodified microplastic group,a negatively charged microplastic group,and a positively charged microplastic group using a random number table,with 12 mice in each group.The mice in the control group were given ddH2O by gavage;the mice in the unmodified microplastic group were given unmodified polystyrene microplastics by gavage,and the mice in the negatively charged microplastic group and the positively charged microplastic group were given negatively charged polystyrene microplastics and positively charged polystyrene microplastics by gavage,respectively,once a day for 4 consecutive weeks.The body weight,drinking water,and food intake of the mice were detected every week.After gavage,the prostate mass,prostate coefficient,prostate histopathological morphology,inflammatory factor expression,microplastic accumulation in the prostate tissue of the mice,and the mRNA and protein expressions of hypoxia-inducible factor 1α and vascular endothelial growth factor were compared among the groups of mice.RESULTS AND CONCLUSION:(1)With the prolongation of microplastic exposure time,the body weight of mice in the unmodified microplastics group and the positively charged microplastics exposure group was significantly suppressed.(2)After exposure to microplastics,they could enter the urinary system of mice,including prostate and bladder tissue.Among the mice in the positively charged microplastic group,the prostate mass and prostate coefficient increased most significantly.(3)Compared with the control group,the mass concentration and mRNA expression of interleukin 6,interleukin 1β,and tumor necrosis factorα were increased in the prostate tissue of the other three groups of mice(P＜0.05).Among them,the positively charged microplastic group exhibited most obvious increase.(4)Hematoxylin-eosin staining showed that the prostate tissue of mice in the unmodified microplastic group,negatively charged microplastic group,and positively charged microplastic group showed obvious proliferation of prostate epithelial cells and matrix,a significant increase in acini,and infiltration of a large number of inflammatory cells.Masson and Sirius red staining showed that compared with the control group,the prostate tissue of mice in the other three groups had obvious fibrosis.Immunohistochemical staining showed that compared with the control group,angiogenesis in the prostate tissue of mice increased in the other three groups(P＜0.05).(5)Compared with the control group,the mRNA and protein expressions of hypoxia-inducible factor 1αand vascular endothelial growth factor were increased in the prostate tissue of the other three groups of mice(P＜0.05),among which the negatively charged microplastic group and the positively charged microplastic group exhibited more significant increase.(6)The results show that polystyrene microplastics can enhance the release of inflammatory factors in mouse prostate tissue,promote angiogenesis in prostate tissue by activating the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway,and provide nutrition support for prostate hyperplasia and fibrosis.