ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

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.

Objective To develop a system for retrieving information from clinical records of Traditional Chinese Medicine(TCM)based on generative large language models(LLMs).Methods Applicational needs of the system were analyzed,and entity types to be retrieved were identified.The functions,workflows,and architecture of the system were designed by combining the automatic retrieval capabilities of LLMs with human-in-the-loop(HITL).The software was developed using such frameworks as vLLM and Node.js.Interaction of multiple commercial/open source LLMs was implemented using OpenAI-compatible interfaces.The quality of information retrieved from LLMs was enhanced by prompt engineering.Results This system supported task allocation,automatic retrieval of structured information,and manual review.To evaluate its performance,the moonshot-v1-8k model was used to retrieve clinical records of TCM before manual edition was performed.Combining large language model pre-annotation with meticulous annotator edits improved accuracy by 26.6％compared to the BERT-BiLSTM-CRF model,and enhanced extraction efficiency by 1.6-fold relative to purely manual methods.Conclusion General generative LLMs can retrieve a wide range of entity information from TCM records with high accuracy and scalability.The design and implementation of this system approach may provide a useful reference for developing other biomedical information retrieval systems.

Hematologic malignancies,such as lymphoma,myeloma,and myeloid neoplasms,can occur in extramedullary tissues.Traditional histopathological morphology and immunohistochemical staining have lim-itations,including time-consuming specimen processing,prolonged reporting cycles,and relatively low sensi-tivity in cases of limited cell numbers.Flow cytometry offers significant advantages in detecting tissue sam-ples,such as rapid processing,shorter reporting cycles,and high accuracy and sensitivity,making it an effective complement to histopathological and immunohistochemical methods.However,the application of flow cytome-try in tissue sample detection currently lacks standardized protocols for sample collection and preservation,single-cell suspension preparation,antibody panel design for limited samples,data analysis,and result repor-ting.To promote the standardized application of flow cytometry in detecting hematologic tumor cells in tissue samples,the Cell Analysis Professional Committee of the Chinese Society of Biotechnology organized experts to develop the Chinese Expert Consensus on Flow Cytometry for Detecting Hematologic Tumor Cells in Tis-sue Samples(hereinafter referred to as the Consensus).This Consensus elaborates on the technical aspects of flow cytometry for tissue sample detection,covering sample processing,antibody panel design,data analysis,reporting content,and quality management.It particularly emphasizes recommended antibody panels and data analysis methods for flow cytometry when tissue sample cell counts are low.This article aims to interpret the key points of the Consensus to facilitate its better application in clinical practice.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)％,(43.73±1.30)％,(30.87±1.27)％and(28.28±1.43)％;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.

Objective To explore the predictive value of dose surface histogram(DSH)in image guided radiotherapy(IGRT)for radiotherapy-induced acute radiation proctitis(ARP)in cervical cancer(CCA).Methods Totally 380 patients with CCA IGRT admitted to some hospital from May 2019 to May 2023 were selected prospectively and randomly divided into a control group(n=1 80)and an experimental group(n=200).The patients in the 2 groups were followed up and the incidence rates of ARP were counted,and rectal dose distribution was evaluated using dose volume histogram(DVH)in the control group and DSH in the experimental group.The predictive values of DVH and DSH for ARP were evaluated and compared using ROC curves.Statistical analysis was performed using SPSS 21.0 software.Results The two groups did not have statistically significant difference in the incidence rate of ARP(P＞0.05),while there were significant differences in the evaluation indicators of the rectal dose distribution(P＜0.05).V40,V50,S40 and S50 proved to have low predictive values for grade Ⅰ-Ⅳ ARP with AUC 0.700(P＜0.05);V60 and S60 had moderate predictive values for grade Ⅰ-Ⅳ ARP with AUC greater than 0.700 and less than or equal to 0.900(P＜0.05);V70,V78,S70 and S7s showed high predictive values for grade Ⅰ-Ⅳ ARP with AUC higher than 0.900(P＜0.05).Delong's test results indicated that DVH and DSH had no significant differences in AUC when used to predict gradeⅠ-Ⅳ ARP(allP＞0.05).Conclusion DSH is essentially the same as DVH when used for the prediction of grade Ⅰ-Ⅳ ARP due to CCA IGRT,and thus can be used for the supplementation and optimization of radiotherapy planning systems.[Chinese Medical Equipment Journal,2025,46(3):48-53]

OBJECTIVE: To assess the value of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score combined with PSA density (PSAD) in the diagnosis of clinically significant prostate cancer (CSPCa) in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy. METHODS: This retrospective study included 327 male patients with total PSA (tPSA) levels of 4-10 μg/L undergoing MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy in our hospital between January 2021 and December 2023. According to the pathological results, we divided the patients into a CSPCa (n = 44) and a non-CSPCa group (n = 283), collected their clinical and imaging data, and subjected them to statistical analysis. RESULTS: The age, tPSA level, PSAD and PI-RADS score were significantly higher, while the free PSA (fPSA) level, f/tPSA ratio and prostate volume remarkably lower in the CSPCa than in the non-CSPCa group (P<0.05). The areas under the curve (AUCs) of PSAD, PI-RADS score and their combination were 0.772, 0.730 and 0.801, with sensitivities of 63.63%, 70.45% and 72.73%, and specificities of 84.10%, 75.62% and 83.75%, respectively (P<0.01). With PSAD 0.2 μg/(ml·cm3) as the best cut-off value and based on the PI-RADS scores, the patients were divided into two groups for analysis. In the patients with PI-RADS scores 2 and 5, the AUCs were 0.534 and 0.643, with sensitivities of 16.67% and 63.64%, and specificities of 85.14% and 64.29%, with no statistically significant differences (P= 0.784, P= 0.228), and in those with PI-RADS scores 3 and 4, the AUCs were 0.794 and 0.843, with sensitivities of 57.14% and 80.00%, and specificities of 87.14% and 81.82%, with statistically significant differences (P= 0.009, P<0.001). CONCLUSION PI-RADS v2.1 score combined with PSAD can effectively improve the diagnostic efficiency of CSPCa in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy and serve as a guide for selection of prostate biopsy.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Retrospective Studies ; Prostate-Specific Antigen ; Magnetic Resonance Imaging ; Image-Guided Biopsy ; Prostate/pathology* ; Aged ; Middle Aged

OBJECTIVE: To evaluate the effects of Chinese patent medicine Huatuo Zaizao Pill (HTZZ) on neurological function and limb motor in ischemic stroke (IS) patients during convalescence. METHODS: This is a prospective, open-labelled, randomized controlled trial. Patients with IS were recruited from the Neurology Department of Xiyuan Hospital of China Academy of Chinese Medical Sciences from May 2021 to June 2023. Eligible participants were randomly assigned to the HTZZ (40 cases) or control group (40 cases) at a ratio of 1:1. The HTZZ group was treated with oral HTZZ (8 g, thrice daily) combined with conventional treatment, while the control group received only conventional treatment. The treatment duration was 12 weeks. The primary outcome was the change in Modified Ashworth Scale (MAS) score from baseline to week 6 and 12. Secondary outcomes included changes in scores of National Institute of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FM), and Barthel Index (BI) from baseline to week 6 and 12, as well as lipid indices after 12 weeks. All adverse events (AEs) were recorded and liver and kidney indices were evaluated. RESULTS: A total of 72 patients completed the study (38 in the HTZZ group and 34 in the control group). Compared with the control group, the HTZZ group demonstrated significant improvements in MAS, NIHSS, FM, and BI scores following 6 and 12 weeks of treatment in both intent-to-treat and per-protocol analyses (all P<0.05). No significant differences were noted between groups in lipid indices, AEs, and liver and kidney dysfunction after 12 weeks (P>0.05). CONCLUSIONS HTZZ alleviated spasticity and enhanced neurological function and prognosis of IS patients during convalescence. However, further evaluation of HTZZ's effect on IS outcomes is warranted in clinical trials with larger sample sizes and extended observation periods. (Trial registration No. NCT04910256).
Humans ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Ischemic Stroke/physiopathology* ; Middle Aged ; Aged ; Recovery of Function/drug effects* ; Convalescence ; Extremities/physiopathology* ; Treatment Outcome ; Prospective Studies

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*