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.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective: To investigate the potential efficacy and safety of Lutai Danshen Baishao granules (LDBG) for treating female melasma associated with kidney deficiency and blood stasis patterns. Methods: A randomized, double-blind, placebo-controlled trial was conducted at the Third Central Hospital of Tianjin, China from March to December 2023. A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days. Efficacy was assessed through measures such as the total melasma area, reduced melasma area, reduction rate of melasma area, melasma color score, Melasma Area and Severity Index (MASI) score, and traditional Chinese medicine (TCM) symptom score scale. Safety assessments included routine blood and biochemical tests. Results: Participants in both groups were aged 52–63 years, with no significant differences. After the 2-month intervention, the total melasma area decreased in both groups; however, a greater reduction was observed in the test group [462.50 mm2 (12.81%) vs. 100.00 mm2 (3.11%), P < .001]. Moreover, LDBG treatment significantly reduced the MASI and melasma color scores in the test group (P < .05). The total TCM symptom evaluation score significantly decreased (test group: 6.00 vs. placebo group: 7.00, P = .001), with significant relief in symptoms such as improvement in dark lips, nails, and waist soreness in the test group, compared with that in the placebo group (P < .05). Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group (P < .05). Conclusion LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.

Objective To investigate the application value of 320-slice wide-detector multi-phase left at-rial appendage computed tomography angiography(LAA-CTA)with pulmonary artery(PA)monitoring in the preoperative evaluation of left atrial appendage closure.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent LAA-CTA before left atrial appendage closure.Among them,47 patients underwent single-phase enhanced scanning with superior vena cava(SVC)monitoring(con-trol group),and 63 patients underwent multi-phase enhanced scanning with pulmonary artery monitoring(study group).The differences in imaging effects of the left atrial appendage under different monitoring points and phase imaging methods were compared,as well as the accuracy of comparing with the diagnostic results of transesophageal ultrasound(TEE),and the differences in the presentation of thrombus,perithrombus,and hypoperfusion areas in the left atrial appendage.Results The study group could comprehensively display the multi-phase CT value changes of different components(thrombus,peri-thrombotic viscosity,normal blood)within the left atrial appendage cavity,and its evaluation of lesion size and progression was superior to that of the control group.Using TEE as the gold standard,the study group demonstrated better diagnostic ac-curacy for different components and normal regions within the left atrial appendage cavity compared to the control group(P<0.001).Additionally,the study group improved the detection rate of peri-thrombotic vis-cosity,clearly delineated thrombus boundaries,and enhanced diagnostic accuracy(P<0.001).Conclusion Multi-phase LAA-CTA with pulmonary artery monitoring can effectively evaluate the morphological dimensions,thrombus,and peri-thrombotic CT manifestations of the left atrial appendage.It is simple to operate,with an accuracy rate close to the gold standard,providing reliable imaging evidence for preoperative evaluation of left atrial appendage closure.

Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis（PNAC）in extremely/ultra-low birth weight infants，and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020，using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software，and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included，with a median gestational age of 29.14（28.00，30.86）weeks and a median birth weight of 1　170（1　000,1　300）g.Among them，26（12.81%）cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition（ OR=1.015 ，95% CI 1.003-1.034），the cumulative amount of glucose（ OR=1.014 ，95% CI 1.001-1.028），small for gestational age（ OR=3.455 ，95% CI 1.127-10.589），and neonatal sepsis（ OR=3.142 ，95% CI 1.039-9.503）were independent risk factors for PNAC（ P＜0.05）；The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model，the area under the receiver operating characteristic curve was 0.835（95% CI 0.842-0.731），and the results of the Hosmer Limeshow goodness of fit test show that：χ 2=5.34，degree of freedom=8， P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate，with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition，glucose accumulation，small for gestational age infants，and neonatal sepsis exhibits high predictive ability，and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

Nesfatin-1 is a neuropeptide hormone known for its biological functions,including inhibiting food intake,regulating glucose and lipid metabolism,promoting apoptosis,and providing anti-inflammatory and anti-tumor effects.Glucose metabolism is a crucial pathway for the body's energy supply.Current research has demonstrated that Nesfatin-1 can affect glucose metabolism through various mechanisms,such as inhibiting food intake,regulating enzyme activity,and improving insulin resistance,though the findings are not entirely consistent.Investigating the relationship between Nesfatin-1 and glucose metabolism may offer new insights into the diagnosis and treatment of diseases related to glucose metabolism disorders.

Based on the Delphi method, combined with the results of the previous literature study and expert interviews, 3 rounds of expert consultation were conducted to evaluate the degree of concentration of expert opinions and their importance from 3 aspects: arithmetic mean, full score ratio ( Ki), and rank sum ( Si), to construct a diagnostic scale for rheumatoid arthritis (RA) cold-dampness syndrome. In this study, 30 expert questionnaires were distributed in the 1st round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.309; 30 expert questionnaires were distributed in the 2nd round, 30 questionnaires were recovered, and the expert coordination coefficient was 0.320; and 30 expert questionnaires were distributed in the 3rd round, 29 questionnaires were recovered, and the expert coordination coefficient was 0.387. The maximum value of the coefficient of variation of the experts of the 3 rounds was 0.27, and the minimum value was 0.09, suggesting that the consistency and credibility of the experts' evaluation of the importance of the entries of cold-dampness syndrome were high. In this study, the mean values and weights of 17 entries were finally obtained, of which the top 5 entries were cold pain in joints (4.793, 0.066 6); aggravated by cold (4.586, 0.063 7); white tongue coating (4.552, 0.063 2); aggravated in cloudy and rainy days (4.448, 0.061 8); and painful joints that are not warm to the touch (4.379, 0.060 8). This study completed the screening of relevant entries and conducted preliminary discussions, laying the foundation for constructing a diagnostic scale for RA cold-dampness syndrome and forming the final diagnostic criteria. The research method is scientific and reliable, which can provide reference for the diagnostic standard of RA cold-dampness syndrome, but further clinical practice research is still needed.

ObjectiveTo construct a research framework for systematic review of health and functional outcomes of whole body vibration training in children and adolescents with cerebral palsy based on the theory and method of World Health Organization Family of International Health Classifications (WHO-FICs), and to systematically review the major health conditions and physical functions, intervention programs of whole body vibration training, and health and functional outcomes of vibration intervention in children and adolescents with cerebral palsy. MethodsBased on the WHO-FICs method, the PICO architecture of systematic reviews was constructed, and the databases of CNKI, Wanfang Data, PubMed, Web of Science, EBSCO, and Embase were searched to collect randomized controlled trials about the health and functional effects of whole body vibration training on children and adolescents with cerebral palsy from the establishment to September 30th, 2022, and a systematic review was conducted. ResultsEight articles, seven in English and one in Chinese, from five countries, were included, mainly from journals in clinical rehabilitation, neurorehabilitation, physical medicine and rehabilitation, etc., published mainly after 2010, involving 227 participants (three to 12.3 years old). The quality of the articles was evaluated using the Physical Therapy Evidence Database scale with a mean score of six. The ICD-11 codes included 08 diseases of the nervous system, 8D20 spastic cerebral palsy, 8D20.1 spastic bilateral cerebral palsy, 8D20.10 spastic quadriplegia cerebral palsy and 8D2Z unspecified cerebral palsy. The primary functioning of cerebral palsy was characterized as muscle spasticity, abnormal skeletal development, joint deformities and muscle weakness, decrease of selective motor control and gait abnormalities; for the activity and participation, the functioning included walking difficulties, decrease of mobility and weight loading, and low levels of physical activities. The main intervention was whole body vibration, in postures of lying, squatting or standing, mainly standing, in the mode of vertical vibration. The frequency was 5 to 30 Hz, and the amplitude was below 9 mm, three to five times a week for eight weeks to six months. The intervention settings include medical institutions, schools and families; mainly for therapeutics and recovery. The health and health-related outcomes were mainly involved s7 structures related to movement, b710 mobility of joint functions, b730 muscle power functions, b735 muscle tone functions, b760 control of voluntary movement functions, d410 changing basic body position, d415 maintaining a body position, d450 walking, d455 moving around, and d420 transferring oneself; such as improvements of neuromusculoskeletal and joint functions, muscle spasm, static balance, muscle strength, and control of movement, the control of body posture and walking, range of activities and self-care. ConclusionWhole body vibration training is effective on cerebral palsy, mainly in standing position, 5 to 30 Hz, and amplitude below 9 mm; three to five times a week for eight weeks to six months. The outcomes of whole body vibration training are mainly reflected in the improvement of body-motor functions, and activity and participation.

Plant metabolites are important for plant development and human health. Plants of celery (Apiumgraveolens L.) with different-colored petioles have been formed in the course of long-term evolution. However, the composition, content distribution, and mechanisms of accumulation of metabolites in different-colored petioles remain elusive. Using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), 1159 metabolites, including 100 lipids, 72 organic acids and derivatives, 83 phenylpropanoids and polyketides, and several alkaloids and terpenoids, were quantified in four celery cultivars, each with a different petiole color. There were significant differences in the types and contents of metabolites in celery with different-colored petioles, with the most striking difference between green celery and purple celery, followed by white celery and green celery. Annotated analysis of metabolic pathways showed that the metabolites of the different-colored petioles were significantly enriched in biosynthetic pathways such as anthocyanin, flavonoid, and chlorophyll pathways, suggesting that these metabolic pathways may play a key role in determining petiole color in celery. The content of chlorophyll in green celery was significantly higher than that in other celery cultivars, yellow celery was rich in carotenoids, and the content of anthocyanin in purple celery was significantly higher than that in the other celery cultivars. The color of the celery petioles was significantly correlated with the content of related metabolites. Among the four celery cultivars, the metabolites of the anthocyanin biosynthesis pathway were enriched in purple celery. The results of quantitative real-time polymerase chain reaction (qRT-PCR) suggested that the differential expression of the chalcone synthase (CHS) gene in the anthocyanin biosynthesis pathway might affect the biosynthesis of anthocyanin in celery. In addition, HPLC analysis revealed that cyanidin is the main pigment in purple celery. This study explored the differences in the types and contents of metabolites in celery cultivars with different-colored petioles and identified key substances for color formation. The results provide a theoretical basis and technical support for genetic improvement of celery petiole color.
Anthocyanins ; Apium/metabolism* ; Chlorophyll/metabolism* ; Color ; Gene Expression Regulation, Plant ; Humans ; Metabolomics ; Plant Proteins/genetics* ; Tandem Mass Spectrometry

Objective:To analyze the dosimetric differences of volumetric modulated arc therapy (VMAT) plans for lung cancer caused by different dose calculation algorithms and radiation field settings and thus to provide a reference for designing clinical VMAT plans for lung cancer.Methods:This study randomly selected 20 patients with lung cancer and divided them into four groups of VMAT plans, namely, a group adopting two fields and two arcs based on the AAA algorithm (2F2A_AAA), a group employing two fields and two arcs based on the AXB algorithm (2F2A_AXB), a group using two fields and two arcs based on the MC algorithm (2F2A_MC), and a group adopting one field and two arcs based on the MC algorithm (1F2A_MC). Then, this study evaluated the target coverage, high-dose control, dose homogeneity index (HI), conformity index (CI), and organs at risk (OARs) of the plans using different algorithms and radiation field settings.Results:The planning target volume (PTV) results of two fields combined with two arcs (2F2A) of three groups using different algorithms are as follows. 2F2A_MC achieved better results in both D1% and V 95% (the relative volume of the target volume surrounded by 95% of the prescribed dose) of planning gross target volume (PGTV) than 2F2A_AAA (D1%: t=-2.44, P=0.03; V95%:z=-2.04, P=0.04) and 2F2A_AXB (D1%: t=2.34, P=0.03; z=-3.21, P < 0.01). 2F2A_AXB outperformed 2F2A_AAA ( z=-3.66, P < 0.01) and was comparable to 2F2A_MC in terms of the CI of PGTV. Regarding OARs, 2F2A_AXB and 2F2A_MC decreased the V5 Gy of the whole lung by 0.68% ( z=-2.69, P=0.01) and 3.05% ( z=-3.52, P < 0.01), respectively compared to 2F2A_AAA. 2F2A_AXB achieved a whole-lung Dmean of 1776.44 cGy, which was superior to that of 2F2A_MC ( t=2.67, P=0.02) and 2F2A_AAA ( t=8.62, P < 0.01). Compared to 2F2A_AAA and 2F2A_MC, 2F2A_AXB decreased the V20 Gy of Body_5 mm by 1.45% ( z=-3.88, P < 0.01) and 2.01% ( z=-3.66, P < 0.01), respectively. The results of the two groups with different field settings showed that 1F2A_MC was superior to 2F2A_MC in both the CI of PTV1 and the HI of PTV2 (CI: t=2.61, P=0.02; HI: z=-2.20, P=0.03). Moreover, 1F2A_MC increased the Dmean of the whole lung by 26.29 cGy compared to 2F2A_MC ( t=2.28, P=0.04). Conclusions:Regarding the design of VMAT plans for lung cancer, the MC algorithm is suitable for the target priority and the AXB algorithm is suitable for the OAR priority. When only the MC algorithm is available, it is recommended to choose 1F2A in the case of target priority and select 2F2A in the case of OAR priority.