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.

ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.