ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

Hyperthermic intrathoracic chemotherapy (HITHOC) is a localized treatment that combines hyperthermia with medications such as chemotherapy, anti-angiogenic agents, targeted therapy, or immunotherapeutic agents. It has advanced clinical progress for conditions such as malignant pleural mesothelioma, pleural metastasis of lung cancer, and pleural dissemination of thymic tumors. Systematic analyses indicate that as an adjuvant therapy to cytoreductive surgery, HITHOC improves patient survival and effectively controls pleural effusion and pleural metastasis. It exerts antitumor effects by enhancing drug penetration through thermal effects, inducing apoptosis, and modulating the immune microenvironment. HITHOC combined with systemic therapies (e.g., chemotherapy, targeted therapy, and immunotherapy) demonstrates synergistic potential, but its role as a local treatment should be clearly defined as adjunctive within the comprehensive management of advanced-stage patients. Further research is needed to clarify its indications, standardized protocols, and long-term efficacy and to explore optimized regimens and personalized combination treatment strategies. This review delves into the key bottlenecks hindering the development of hyperthermia therapy, such as the lack of high-level evidence-based medicine and the absence of standardized diagnostic and efficacy evaluation criteria, and proposes potential solutions.

[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×10¹²/L, Hb 10⁶ g/L, HCT 30.40%, PLT 115.00×10⁹/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×10¹²/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×10⁹/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.

Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.

Circulating tumor cells (CTCs) have the ability to sow tumors and can be found in the peripheral blood of patients with precancerous lesions and healthy people. However, CTCs are not currently screened in the donors blood. A large number of allogeneic blood transfusions occurred worldwide each year, and allogeneic blood transfusions expose recipients to the risk of transmission and affect tumors associated with donor CTCs. Although leukocyte filtration can not completely remove tumor cells in the blood, it can effectively reduce the number of white blood cells in the blood and reduce their proliferation ability. Blood irradiation can effectively destroy the DNA of CTCs in the blood, and inhibit the occurrence and metastasis of tumors caused by the infusion of allogeneic blood containing CTCs. Therefore, we should pay attention to the potential risk of CTCs on clinical transfusion, and strengthen the preclinical treatment of blood to avoid donor-related tumor infection in blood recipients due to clinical transfusion.

Objective To establish an effective model for distinguishing glandular prodromal lesions(PGL)mixed with ground-glass nodules(mGGN)from minimally invasive adenocarcinoma(MIA)on CT based on artificial intelligence.Methods A retrospective analysis was conducted on the clinical and CT image data of 180 patients with lung adenocarcinoma confirmed by surgical pathology and with CT manifestations of mGGN in the First Affiliated Hospital of Wenzhou Medical University from January 2017 to June 2023,inclu-ding 66 patients with PGL and 114 patients with MIA.Patients were divided into the training set(n=144)and the test set(n=36)in an 8∶2 ratio using a completely random method.The quantitative parameters and radiomics features of the lesions in CT images were automatically extracted using artificial intelligence soft-ware(United Imaging Research Platform uRP).By incorporating the most obvious correlation features of omics through dimensionality reduction,five machine learning classifiers were established,including logistic regression(LR),support vector machine(SVM),Random forest(RF),Gaussian process(GP),and Decision Tree(DT).The classifier with the training set highest area under the curve(AUC)was selected as the best radiomics model,and output the result as radiomics score(Rad-score).The clinical information,CT morpho-logical characteristics and quantitative data of the two groups were included in the multivariate logistic regres-sion analysis to screen the independent influencing factors for effectively differentiating PGL and MIA,and a clinical model was established.Finally,a comprehensive prediction model was constructed based on Rad-score and clinical risk factors.The diagnostic performance of the three models was evaluated by using the AUC,sen-sitivity,specificity and accuracy of receiver operating characteristic(ROC)curve.Results Eleven radiomics features for distinguishing PGL from MIA were obtained through LASSO dimensionality reduction.Among the five machine learning classifiers,GP has the best diagnostic performance,with AUC of 0.865 in the train-ing set and 0.762 in the test set,respectively.Univariate and multivariate logistic regression analyses were used for clinical feature screening.The clinical model was constructed by using the average CT value,average long and short diameter,and solid partial long diameter of mGGN,and the AUCs of the training set and the test set were 0.870 and 0.794,respectively.The comprehensive prediction model demonstrated superior diag-nostic performance,with AUC,sensitivity,specificity,and accuracy in the training set being 0.948,81.1%,91.2%and 87.5%respectively,while 0.883,76.9%,91.3%and 86.1%respectively in the test set.Conclu-sion The comprehensive prediction model established based on the quantitative and omics feature analysis of pulmonary nodules by artificial intelligence can well distinguish mGGN mixed with PGL from MIA on CT,and can be used to guide clinical treatment decisions.

Objective To investigate the effect of propofol on bone metabolism in glucocorticoid induced osteoporo-sis(GIOP)in rat models by regulating the PI3K/AKT/mTOR signaling pathway.Methods Rats were grouped into a blank group,model(GIOP)group,2.5 mg/kg and 5 mg/kg propofol groups and a propofol+LY294002(5 mg/kg propofol+5 mg/kg LY294002)group,with 12 rats in each group.A small animal bone densitometer was used to measure the tibial bone density(BMD)of rats.ELISA was applied to detect the level of bone gla-protein(BGP),procollagen Ⅰ N-terminal propeptide(PINP)and type Ⅰ collagen cross-linked C-terminal peptide(CTX-Ⅰ)in rat serum.HE staining microscopy was applied to observe the pathological morphology of rat bone tis-sue.RT-qPCR was used to detect the mRNA expression of Pi3k,Akt,mTor,Beclin-1,and p62 in bone tissue.Western blot was used to detect the expression level of PI3K/AKT/mTOR signaling pathway related proteins and autophagy related proteins in rat bone tissue.Results Compared with the blank group,the tibial BMD,serum BGP,and CTX-Ⅰ levels of GIOP group decreased(P＜0.05).mRNA expression of Pi3k,Akt,mTor and Beclin-1 in bone tissue decreased(P＜0.05).mRNA and protein expression of p62 increased(P＜0.05).The expression of PI3K/AKT/mTOR signaling pathway related proteins and Beclin-1 protein in bone tissue decreased(P＜0.05).Compared to GIOP group,the changes of above indicators were obviously alleviated in the 2.5 mg/kg and 5 mg/kg propofol groups(P＜0.05).On the basis of treatment with 5 mg/kg propofol,the use of LY294002 inhibited activation of the PI3K/AKT/mTOR signaling pathway and autophagy and interfered with the positive regulatory effects of propofol on bone me-tabolism and bone tissue morphology improvement in GIOP rats(P＜0.05).Conclusions Propofol may improve bone metabolism in rat models of GIOP through potential mechanism of activating PI3K/AKT/mTOR signaling pathway.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective To investigate the alteration of M1/M2 polarization of monocyte-macrophages from the peripheral blood of patients with active pulmonary tuberculosis,and the effect of Mycobacterium tuberculosis ESAT6 on the polarization of human THP-1 cells.Methods Whole blood and serum samples were collected from 14 patients with active pulmonary tuberculosis and 10 healthy controls.Peripheral blood mononuclear cells(PBMCs)were isolated from whole blood with heparin sodium using lymphocyte fluid.The mRNA levels of HLA-DR,CD11C,CD68,CD206 and Arg-1 in PBMCs from patients with active pulmonary tuberculosis were detected by real-time quantitative PCR.The secretion of cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-4,etc.)was detected by flow cytometry.Human THP-1 cells were induced by phorbol ester(PMA)to differentiate into macrophages-like cells,which were divided into M0 group,M1 group,M2 group,and M0+ESAT6 group.After 24 hours of stimulation,the mRNA levels of HLA-DR,CD11C,CD68,CD206 and Arg-1 were detected by real-time PCR.Following stimulation with ESAT6 for 6 h,12 h and 24 h,the levels of cytokines(IL-2,IL-6,TNF-α,IL-4,etc.)in cell culture supernatant from THP-1 cells were detected by flow cytometry.Results Compared with the healthy control group,the mRNA expression levels of M1-polarized phenotypic molecules HLA-DR,CD11C and CD68 in PBMCs of the active pulmonary tuberculosis group were up-regulated(P<0.05).The mRNA expression level of M2-polar-ized phenotype molecule CD206 was decreased(P<0.05),while the expression level of Arg-1 mRNA was not statistically significant(P>0.05).Serum levels of M1-related proinflammatory cytokines IL-2,IL-6,IFN-γ and TNF-α were increased in patients with active pulmonary tuberculosis(all P<0.05),whereas decreased level of anti-inflammatory cytokine IL-4(P<0.05)were found in serum samples from patients with active pulmonary tuber-culosis.THP-1 macrophages were induced to differentiate into different phenotypes in vitro,and the HLA-DR mRNA expression level of cell M1 polarization phenotype molecule was statistically significant among all groups(F=21.83,P=0.000).Pairwise comparison results showed that expressions of HLA-DR mRNA in M1 group and M0+ESAT6 group were significantly upregulated compared with M0 group(P<0.05),there was no significant difference between the other groups(P>0.05).However,there was no significant difference in the expression of CD68 mRNA among all groups(F=2.480,P=0.135).There was no significant difference of mRNA expressions of CD206 and Arg-1 among all groups(F=1.233,P=0.3597;F=6.059,P=0.068).There were no significant differences between the M1-related pro-inflammatory cytokine IL-2 and anti-inflammatory cytokine IL-4 at different time points of cell culture(P>0.05).Compared with the M0 and ESAT6 phenotypes,the levels of pro-inflammatory cytokines IL-6 and TNF-α in the M1 phenotype group were significantly increased at 12 h and 24 h(P<0.05,P<0.05,P<0.001,P<0.001;P<0.05,P<0.05,P<0.01,P<0.01);but there was no significant difference between the other groups(P>0.05).Conclusions The ability of peripheral blood monocyte-macrophages to polarize to M1 is enhanced,while the ability to polarize to M2 is weakened in patients with active pulmonary tuberculosis.Mycobacterium tuberculosis ESAT6 can promote the polarization of macrophages to M1,which affects the activity and progression of tuberculosis.

Objective To investigate the effects of dexmedetomidine(Dex)on osteoporosis(OP)rats and possible mechanisms.Methods The rats were divided into sham operation group,osteoporosis model group(OP,replica-ting the OP rat model with bilateral ovariectomies),Dex-L,M,and H(Dex low,medium,and high dose treat-ments)groups and Dex-H+XAV-939 group(Wnt/β-catenin pathway inhibitor).Micro-CT was applied to meas-ure bone mineral density(BMD)and bone microstructure of rat femurs.The three-point bending experiment was applied to analyze the biomechanics of the femur(maximum load,fracture deflection,elastic modulus).HE stai-ning was applied to observe pathological changes in the femur of rats.ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP),typeⅠ procollagen amino-terminal peptide(PINP)and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ).The expression of Runx2 and Wnt3a was examined by Immunohistochemistry.Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue.Results Compared to the Sham group,the bone volume and number of trabeculae in OP group were obviously reduced,the maximum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased,CTX-Ⅰ increased(P＜0.05).Compared to the OP group,the bone trabecular structure in the Dex-L,M,and H groups was restored,the maxi-mum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression all increased but CTX-Ⅰ decreased(P＜0.05).Compared to the Dex-H group,the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage.The maximum load,fracture de-flection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased while CTX-Ⅰ increased(P＜0.05).Conclusions Dex may antagonize OP effects by improving bone density,biomechanical properties and microstructure.The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.