ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.

Objective:To prepare a novel 68Ga-labeled bicyclic peptide targeting poliovirus receptor related protein 4 (PVRL4, Nectin-4), and evaluate its feasibility for breast cancer imaging via in vitro and in vivo experiments. Methods:A Biotin-modified bicyclic peptide targeting Nectin-4, Biotin-BMIC, was synthesized, and its targeting properties were preliminarily evaluated by in vitro cell staining experiments. BMIC was modified by 1, 4, 7-triazonane-1, 4-diacetic acid (NODA) and the labeling precursor NODA-BMIC was prepared. A potential PET probe targeting Nectin-4, 68Ga-NODA-BMIC was prepared by one-step labeling strategy. The imaging properties of the probe were investigated by in vivo microPET imaging and in vitro experiments in mice bearing breast tumors. Data were analyzed by independent-sample t test and repeated measures analysis of variance. Results:Fluorescence staining of the cells showed that the fluorescently labeled bicyclic peptide, Biotin-BMIC, was highly aggregated in Nectin-4 positive BT474 breast cancer cells compared to those in Nectin-4 negative MDA-MB-231 cells. The uncorrected yield of 68Ga-NODA-BMIC was (71.5±2.2)% and the radiochemical purity was greater than 95%. The specific activity was greater than 3 GBq/μmol. After incubation 10, 30, 60 and 120 min, higher radioactivity uptakes were found in BT474 breast cancer cells compared to those in MDA-MB-231 breast cancer cells respectively ( F=1 302.00, P<0.001). MicroPET imaging showed that the BT474 xenograft tumors were clearly visible with favorable contrast. A significant statistical difference in uptakes between BT474 and MDA-MB-231 xenograft tumor uptake at 10, 30, 60, and 120 min after probe injection respectively was existed ( F=1 826.00, P<0.001). At 60 min postinjection, the uptake value of BT474 tumors was (5.03±0.14) percentage activity of injection dose per gram of tissue (%ID/g), which was significantly higher than that of MDA-MB-231 tumors ((0.19±0.04) %ID/g; t=79.40, P<0.001). Meanwhile, the tumor-to-muscle ratios in the former were also greater than those in the latter ( F=222.00, P<0.001). At 60 min postinjection, the tumor-to-muscle ratio in the former was significantly higher than that in the latter (24.75±3.10 vs 1.30±0.15; t=14.31, P=0.002). The results were consistent with the immunohistochemistry staining. Conclusions:A novel bicyclic peptide PET probe targeting Nectin-4, 68Ga-NODA-BMIC, is easy to be synthesized and owns satisfactory labeling yield and radiological purity. The imaging performance is good and the target tissues could be visualized. It may play a unique role in the diagnosis and treatment of breast cancer.

Essential oils (EOs) are natural, volatile substances derived from aromatic plants. They exhibit multiple pharmacological effects, including antibacterial, anticancer, anti-inflammatory, and antioxidant properties, with broad application prospects in health care, food, and agriculture. However, the instability of volatile components, which are susceptible to deterioration under light, heat, and oxygen exposure, as well as limited water solubility, have significantly impeded the development and application of EOs. Porous nanoclays are natural clay minerals with a layered structure. They possess unique structural characteristics such as large pore size, regular distribution, and tunable particle size, which are extensively utilized in drug delivery, adsorption separation, reaction catalysis, and other fields. Natural-derived porous nanoclays have garnered considerable attention for the encapsulation and delivery of EOs. This review comprehensively summarizes the structure, types, and properties of natural-derived porous nanoclays, focusing on the structural characteristics of porous nanoclays such as montmorillonite, palygorskite, halloysite, kaolinite, vermiculite, and natural zeolite. It also examines research advances in their delivery of EOs and explores engineering strategies to enhance the delivery of EOs by natural-derived porous nanoclays. Finally, various applications of natural-derived porous nanoclays for EOs in antibacterial, food preservation, repellent, and insecticide aspects are presented, providing a reference for the development and application of EOs.
Humans ; Nanoparticles/chemistry* ; Oils, Volatile/administration & dosage* ; Porosity ; Nanoparticle Drug Delivery System/chemistry*

Objective:To label mesenchymal stem cells (MSCs) with 89Zr-oxine complex, and assess its characteristics of PET imaging in systemic lupus erythematosus (SLE) model (MRL/lpr mice). Methods:SLE mice were screened by 18F-FDG PET imaging. 89Zr-oxine was prepared and used for labeling MSCs (10 6 MSCs and 1 MBq 89Zr-oxine). 89Zr-oxine-labeled MSCs (0.2 MBq) were injected into MRL/lpr mice and BALB/c mice (each n=5) via tail vein at a dose of 1.2×10 6 cells per mouse, and followed with microPET imaging in vivo at 2 h, 6 h, 1 d, 3 d, 7 d, 10 d and 14 d after injection. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used to analyze the data. Results:MSCs was successfully labeled with 89Zr-oxine, with the labeling efficiency of 20% and cell viability >90%. MicroPET imaging showed that MSCs were mainly distributed in lungs and the liver sites at 2 h after injection. The number of MSCs homing to kidneys of MRL/lpr mice ( n=5) increased significantly 24 h after the injection, and the renal uptake of MSCs in MRL/lpr mice was much higher than that in BALB/c mice ((8.28±1.27) vs (4.33±0.94) %ID/g; t=3.54, P=0.024). The renal uptake increased firstly and then decreased and then leveled off, indicating MSCs homing to kidneys. Conclusions:A method for 89Zr-oxine labeling of MSCs is successfully established. 89Zr-labeled MSCs can home to kidneys of SLE mice. PET imaging of 89Zr-labeled MSCs can be effectively used to explore the in vivo distribution and migration behavior of transplanted MSCs during the treatment of diseases such as SLE.

The vasoactive substance resistance (VSR) in the end-stage liver disease (ESLD) refers as the reduction of patients' responsiveness to endogenous and exogenous vasoactive substances, cardiac and vascular excitability, peripheral circulatory dysfunction, but induction of related adverse events. VSR is closely related to pathogenesis and treatment-related ESLD complications. However, to date, there are so many unsolved issues, like 1). The cause and underlying mechanism of VSR in ESLD patients; 2). VSR and ESLD multiple organ damages; 3). The preventive and mitigated measurement of VSR; and 4). VSR vasoactive drug use in ESLD patients. This review discussed and summarized the up to date progress in this field of research and clinical VSR in patients with ESLD, i.e., VRS in ESLD patients, disputes of vasoconstrictor drug therapy in ESLD patients, and future research direction of the field.

OBJECTIVES: The waiting room for surgery is an area set up to improve the surgical turnover rate, but the waiting time for surgery is uncertain. Patients are prone to negative emotions that affect their physiological state during waiting time. This study aims to explore the effect of Mandala painting intervention based on Mandala-self theory on the emotion and physiological state of patients waiting before operation. METHODS: The patients in the control group ( RESULTS: Diastolic pressure, heart rate, and happiness and excitement showed no statistical significance in the time effect, intervention effect, and interaction between the 2 factors (all CONCLUSIONS The application of Mandala painting in the operation waiting room is feasible and can effectively regulate the patients' negative mood and systolic pressure, as well as shorten the waiting time of perception.
Anxiety ; Emotions ; Heart Rate ; Humans ; Pain ; Waiting Rooms

Objective:To prepare a 68Ga labeled human epidermal growth factor receptor 2 (HER2) affibody 68Ga-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid (NOTA)-maleimide (MAL)-Cysteine (Cys)-Glycine-Glycine-Glycine-Arginine-Aspartic acid-asparagine-HER 2: 342 affibody (GGGRDN-ZHER 2: 342)( 68Ga-MZHER), and evaluate its biodistribution and microPET characteristics. Methods:NOTA-MAL-Cys-GGGRDN-ZHER 2: 342 conjugate was labeled with 68Ga in one step. Radiochemical purity, radiolabeling yield and stability in vitro were analyzed. Normal mice ( n=24) were scarified at 15, 30, 60 and 120 min postinjection (1.85 MBq 68Ga-MZHER) to measure radioactive counts (percentage activity of injection dose per gram of tissue (%ID/g)) in main organs. Biodistribution and kinetics were evaluated by dynamic microPET in mice. Ovarian cancer (SKOV-3) models were established and microPET was performed at 30, 60 and 120 min postinjection of radiotracer. After administration of unlabeled Cys-ZHER 2: 342 peptide (10 mg/kg body weight) for 30 min, 68Ga-MZHER was injected into mice and PET images were acquired at 60 min postinjection. Region of interest (ROI) was drawn to access time-activity curve (TAC) in main organs and tumor. Six normal mice were used for the safety study. Results:68Ga-MZHER was synthesized in about 15 min with the yields more than 90%, and radiochemical purity more than 95%. The radiochemical purity was also determined to be more than 95% after being stored for 120 min at room temperature. Predominant uptake of 68Ga-MZHER was in the kidneys, and was cleared rapidly in normal tissues except the kidney. At 15 min postinjection, the renal uptake value was (106.36±15.74) %ID/g, then gradually increased with time, up to (145.15±28.04) %ID/g (60 min), and decreased to (86.12±22.75) %ID/g after 120 min postinjection. The blood pharmacokinetic of the probe in mice was fit with the two-compartment model. MicroPET imaging in mice bearing HER2 positive SKOV-3 tumors showed that the xenografts were clearly visualized with good contrast to normal tissue. The uptakes in tumors was determined to be (11.26±0.50), (12.27±1.13) and (12.65±0.89) %ID/g at 30, 60 and 120 min postinjection. Block experiment showed that the corresponding values decreased to (1.25±0.28) %ID/g at 60 min postinjection. Safety studies showed that after injection of 68Ga-MZHER for 30 d, the mice survived and no obvious abnormalities were observed in the main organs as shown in pathological results. Conclusions:68Ga-MZHER can be successfully labeled by one-step method. The 68Ga-MZHER probe owns the advantages of favorable imaging properties, convenient preparation, excellent stability, safety, rapid clearance in the blood, which support its application for further research.