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.

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Currently,the first-generation of proton pump inhibitors(PPIs)commonly utilized in clinical practice for the treatment of peptic ulcer include omeprazole,lansoprazole,and pantoprazole,and the second generation include rabeprazole and esomeprazole.The predominant mode of PPI administration is oral,which poses numerous challenges in clinical settings owing to their poor solubility,susceptibility to gastric acid degradation,short half-life,and limited stability.This article presents a comprehensive review of studies exploring the novel states of these five PPIs,include polymorphism,co-crystal drugs,and nanodrugs.Furthermore,it summarizes the advancements in research aimed at modifying the physicochemical properties of these drugs through innovative solid states,thereby enhancing their bioavailability and stability.This work offers a new perspective for researchers endeavoring to develop new states of pharmaceutical substances that incorporate PPIs.

Objective:To investigate the changes and effects of the Wnt/β-catenin pathway during hypoxia-reoxygenation in human renal tubular epithelial(HK-2)cells.Methods:HK-2 cells were randomly divided into control group(Control),model group(Model),model+interference empty vector group(Model+NC),and model+interference group(Model+Si-β-catenin).Cells in the control group were cultured routinely.Cells in the Model group were intervened with hypoxia for 6 hours and reoxygenation for 2 hours to construct a hypoxia-reoxygenation model.HK-2 cells in the Model+NC group and the Model+Si-β-catenin group were transfected with β-catenin interference empty vector and β-catenin interference vector respectively,and then a hypoxia-reoxygenation model was constructed.After corresponding interventions,cells were collected.The apoptosis of cells in each group was detected by flow cytometry.The expression of matrix metalloproteinase-7(MMP-7)and α-smooth muscle actin(α-SMA)was detected by immunofluorescence.The expression level of Wnt pathway-related proteins was detected by Western blotting.Results:Compared with that in the control group,the apoptosis rate of cells in the Model group was significantly up-regulated,and there was no significant difference in cell apoptosis between the Model group,the Model+NC group and the Model+Si-β-catenin group.The results of WB detection showed that there was no significant difference in the expression of GSK-3β protein in the cells among the control group,the model group,the model+NC group and the model+Si-β-catenin group.Compared with that in the control group,the expression of p-GSK-3β protein in the Model group was significantly up-regulated,while there was no significant difference in the expression of p-GSK-3βprotein between the Model group,the Model+NC group and the Model+Si-β-catenin group.The results of immunofluorescence detection showed that MMP-7 and α-SMA in the Model group were significantly increased compared with that in the control group,while there was no significant difference between the Model group and the Model+NC group.Compared with the Model+NC group,MMP-7 and α-SMA in the Model+Si-β-catenin group were significantly down-regulated.Conclusion:The Wnt/β-catenin pathway is activated in HK-2 cells during hypoxia-reoxygenation and promotes the expression of fibrosis-related proteins.Inhibiting β-catenin can improve its fibrosis induction level.

Objective:To investigate the risk factors and construct a nomogram prediction model for neonatal bacterial meningitis (BM).Methods:A retrospective cohort study was conducted on 1 228 neonates who underwent lumbar puncture for cerebrospinal fluid examination in the Department of Neonatology at Gansu Provincial Women and Child Healthcare Hospital from December 2019 to February 2024. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 7∶3 using a computer program. Rank sum test or Chi-square tests were used to compare differences between the two cohorts. The subjects were divided into BM and non-BM groups based on the presence or absence of BM. Multivariate logistic regression analysis (forward stepwise regression method) was used in the training cohort to identify risk factors for BM. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess the discrimination and calibration of the model, respectively. Calibration curves were used to evaluate the accuracy of the model and to construct the nomogram. Internal validation was performed using the Bootstrap resampling method. Decision curve analysis was used to assess the clinical utility of the model. Results:Among the 1 228 neonates, 151 (12.3%) had BM. The training cohort included 859 neonates, of whom 106 (12.3%) had BM and 753 (87.7%) did not. The validation cohort included 369 neonates, of whom 45 (12.2%) had BM and 324 (87.8%) did not. The results of the multivariate logistic regression analysis in the training cohort showed that sepsis ( OR=4.446, 95% CI:2.583-7.653), convulsions ( OR=3.749, 95% CI:1.930-7.280), high maximum body temperature ( OR=2.027, 95% CI:1.636-2.513), and elevated C-reactive protein ( OR=1.007, 95% CI:1.003-1.012) were independent risk factors for BM, while greater gestational age at birth ( OR=0.946, 95% CI: 0.898-0.995) and higher hemoglobin levels ( OR=0.990, 95% CI:0.981-0.998) were protective factors for BM (all P<0.05). Based on these findings, a nomogram prediction model for neonatal BM was constructed and validated for accuracy. The AUC values of the nomogram model in the training and validation cohorts were 0.796 (95% CI: 0.750-0.843) and 0.781 (95% CI: 0.700-0.862), respectively. The Hosmer-Lemeshow goodness-of-fit test showed P>0.05 in both cohorts. The clinical decision curve analysis demonstrated good net benefit across most threshold ranges. Conclusions:Sepsis, convulsions, high maximum body temperature, and elevated C-reactive protein increase the risk of neonatal BM. The nomogram model constructed based on these factors, combined with gestational age and hemoglobin levels, provides a reference value for predicting the risk of neonatal BM.

Objective To propose an improved YOLOv8 algorithm based on polarized self-attention(PSA)and deformable attention(DAT)so as to enhance the detection of pulmonary nodules in CT images.Methods A basic framework was established with a YOLOv8 model consisting of a backbone network(Backbone),a neck module(Neck)and a head module(Head).PSA was introduced into the end of the spatial pyramid pooling-fast(SPPF)of Backbone to construct a YOLOv8-PSA algorithm,and DAT was involved in the medium-scale feature layer P4 in Head to form a YOLOv8-DAT algorithm.The YOLOv8-PSA and YOLOv8-DAT algorithms were trained and validated using the CT image dataset of pulmonary nodules from public platforms,and compared with the original YOLOv8 algorithm for the detection of pulmonary nodule lesions in CT images.Results When used for pulmonary module detection of CT images,the YOLOv8-DAT algorithm had the mean average precision(mAP)in case of intersection over union threshold of 0.5(mAP50),mAP in case of intersection over union threshold of 0.5 to 0.95(mAP50-95)and precision ratio being 0.918,0.588 and 0.960 respectively,which gained advantages over the YOLOv8-PSA algorithm with mAP50,mAP50-95 and precision ratio being 0.914,0.583 and 0.945 respectively,and over the original YOLOv8 algorithm with mAP50,mAP50-95 and precision ratio being 0.911,0.564 and 0.952 respectively.Conclusion The YOLOv8-DAT algorithm detects pulmonary modules in CT images effectively,and facilitates early screening and diagnosis of pulmonary modules clinically.[Chinese Medical Equipment Journal,2025,46(8):1-10]

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

AIM To study the chemical constituents of Anaphalis margaritacea(L.)Benth.& Hook.f.and their antioxidant activities.METHODS Separation and purification were performed using silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method and ABTS method.RESULTS Twenty-three compounds were isolated and identified as trans-tilidroside(1),4'-hydroxydehydrokawain(2),apigenin(3),3-O-kaempferol-3-O-acetyl-6-O-(p-coumamoyl)-α-D-glucopyranoside(4),kaempferol(5),quercetin-3-O-β-D-(6-O-Z-p-coumamoyl)-glucopyranoside(6),tiliroside(7),kaempferol-3-O-β-D-glucoside(8),3,5-dihydroxy-7,8-dimethoxyflavone(9),bis(2-ethylhexyl)adipate(10),3,5-dihydroxy-6,7,8-trimethoxyflavone(11),stigmasterol(12),myriophylloside B(13),1-hexadecanol(14),chlorogenic acid(15),4-hydroxy-N-{ 4-[3-(4-hydroxyphenyl)-E-acryloylamino]-butyl}-benzamide(16),3,6-dimethylpiperazine-2,5-dione(17),β-adenosine(18),5,6-dehydrokawain(19),kaempferol-3-O-(2",6"-di-O-E-p-coumaroyl)-β-D-glucopyranoside(20),kaempferol-3-O-(3"-O-E-p-coumaroyl)-(6"-O-E-feruloyl)-β-D-glucopyranoside(21),4,5-di-caffeoylquinic acid butyl ester(22),3,4-di-caffeoylquinic acid butyl ester(23).The IC50 values of compounds 1,7,22-23 against DPPH free radicals were(24.67±1.63)-(53.41±1.61)μmol/L,and the IC50 values of compounds 8,21-23 against ABTS+free radicals were(15.22±0.89)-(41.66±6.29)μmol/L.CONCLUSION Compounds 9,19-23 are isolated from genus Anaphalis for the first time,and 2,10,13,14,16,17,19-23 are first isolated from this plant.Compounds 1,7-8,21-23 have strong antioxidant activity.