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.

Objective: To understand the hydration status and related factors of rural boarding primary school students, so as to provide a scientific basis for drinking water health intervention for primary school students. Methods: In November 2023, a convenience sampling approach was employed to conduct a hydration status survey among 144 boarding students in grades 5 and 6 of a rural primary school in Guangxi. The Duplicate meal method and weighing method were utilized to measure the food derived water intake over three consecutive days. Urine osmolarity of students was measured on site for three days, and a simple physical examination was also carried out. A self administered questionnaire was used to investigate students drinking water literacy, daily water intake, and physical activity levels. Meanwhile, a drinking water literacy survey was conducted among 21 substitute teachers and 144 parents of the boarding students in grades 5 and 6. Logistic regression was used to identify factors associated with students hydration status. Results: The median daily total water intake of students was 2 043.55 mL, and 54.86% of the students did not reach the recommended Adequate Intake (AI). The median food derived water intake was 1 149.24 mL, accounting for 53.94% of the total water intake. Univariate analysis revealed that the daily drinking frequency, daily water intake, and food derived water intake of students were related factors of hydration status ( β =-1.60, -1.01, -0.00, all P <0.05). Multivariate Logistic regression analysis showed that primary school students with a daily drinking frequency of ≥7 times were more likely to maintain an adequate hydration status ( OR =0.28, 95% CI =0.09-0.93, P ＜0.05). Conclusions The water intake from food is the main source of water in the body for boarding primary school students in a certain rural school in Guangxi. Primary school students should increase their water intake frequency appropriately to maintain an adequate hydration status.

Objective: To investigate the current status of knowledge, attitudes and practices regarding drinking water among primary school students in rural areas of China, so as to provide scientific basis for implementing health interventions related to drinking water. Methods: From November to December 2023, a stratified cluster random sampling method was employed to select 6 354 fourth to sixth grade primary school students in Shanxi, Zhejiang, Jiangxi, Guangxi and Gansu for a questionnaire survey. A uniformly designed questionnaire (including basic information, drinking water-related knowledge, attitudes and practices indicators) was distributed and completed by the students themselves. The χ 2 test was used to analyze the differences in drinking water-related indicators among students of different gender and boarder, and Logistic regression was used to analyze the influencing factors of drinking water practices among students. Results: Among the indicators of drinking water knowledge, the awareness rate of appropriate daily water intake for respective student age groups was the lowest (27.90%). The awareness rate among nonresident students was significantly higher than that among boarding students (31.29%, 15.49%, χ 2=132.75, P <0.01). Regarding attitudes toward drinking water, 13.33% of the students believed that well water or tap water could be drunk directly, and 9.58% believed that going to the toilet at school was troublesome. Regarding practices, the self-reported water intake among students was 1 000 (600, 1 200) mL. The results of multifactorial Logistic regression showed that higher grades ( OR=1.60, 95%CI =1.34-1.92), nonresident students ( OR=1.32, 95%CI = 1.15 -1.52), northern region ( OR=1.43, 95%CI =1.27-1.61), knowledge of appropriate daily water intake ( OR=1.41, 95%CI =1.24-1.60), drinking temperature ( OR=1.43, 95%CI =1.28-1.60), scientific hydration methods ( OR=1.25, 95%CI =1.08- 1.44 ), and adopting scientific hydration methods regularly ( OR=1.75, 95%CI =1.50-2.04) were the independent influences on daily water intake attainment ( P <0.05). Conclusions Rural primary school students lack knowledge about healthy drinking water, have cognitive biases about safe drinking water and exhibit unhealthy drinking behavior. It is suggested that health education be carried out in combination with the characteristics of students to enhance their drinking water literacy.

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.

This study analyzed the clinical and laboratory data of 3 children diagnosed with mitochondrial disease-associated primary adrenal insufficiency (PAI) at the Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from October 2018 to November 2023.All patients were normal at birth but gradually developed symptoms and were diagnosed with PAI between the ages of 1 year and 1 month and 7 years and 3 months.The children presented typical clinical symptoms of PAI, including skin and mucosal hyperpigmentation (3 cases), electrolyte disturbances (3 cases), and hypoglycemia (2 cases), as well as multisystem abnormalities related to mitochondrial disease, including recurrent infections, growth retardation, cachexia, and hyperlactatemia.Genetic testing revealed significant single deletions in mitochondrial DNA in all patients: Patient 1: m.11219_15954del, Patient 2: m.8483_13459del, and Patient 3: m.8649_16084del.Treatment with Hydrocortisone acetate replacement therapy improved the electrolyte disturbances and hypoglycemia, but issues with recurrent infections, growth retardation, and cachexia persisted.This study suggests that in clinical practice, the possibility of mitochondrial disease should be highly suspected when PAI patients present with multisystem abnormalities, especially in conjunction with hyperlactatemia.

Objective The aim of this study was to explore the effects of changes in the estrogen receptor alpha 36(ER-α36)expression on the proliferation and membrane-initiated estrogen signaling in glioblastoma U251 cells.Methods The expression and localization of ER-α36 and EGFR glioblastoma U87 cells and U251 cells were determined by immunofluorescence,qRT-PCR and Western blot.The effect of upregulating ER-α 36 on U251 cell proliferation and estrogen signaling pathway activity by low con-centrations of 100 pmol/L icariin isomer(SNG162)was detected by MTT assay and Western blot.Results ER-α36 and EGFR were co-expressed in the cell membrane of glioblastoma.Compared with DMSO(control group),the expression ER-α36(P<0.01)and EG-FR increased in U251 cells treated with SNG162(P<0.05);Further experments also found that low concentrations of SNG162 in-creased the expression of cycle related proteins-cyclin D1,cyclin B,cyclin E and CDK4(P<0.01),and enhanced the proliferative a-bility of U251 cells(P<0.05).Conclusion The low concentration of SNG162 upregulates the expression of ER-α36,activates the estrogen-mediated ERK1/2 MAPK,p38 MAPK,and EGFR/Src signaling pathways,promotes glioblastoma proliferation,and activates the membrane initialized estrogen signaling pathway.

Objective:To explore the effect of multidisciplinary comprehensive nursing intervention on skin itching among maintenance hemodialysis (MHD) patients with malignant tumors.Methods:From July 2021 to December 2023, 69 patients with malignant tumors undergoing MHD admitted to the Fourth Affiliated Hospital of Nanjing Medical University were selected as study subjects using convenience sampling. The study subjects were divided into the control group ( n=34) and the observation group ( n=35) using a random number table method. Patients in the control group received routine nursing, while those in the observation group received multidisciplinary comprehensive nursing, and the intervention period was three months for both groups. Visual Analogue Scale (VAS) scores, Pittsburgh Sleep Quality Index (PSQI) scores before and after intervention, and the incidence of skin adverse events after intervention were compared between the two groups. Results:After the intervention, the VAS, PSQI scores, and incidence of skin adverse events in the observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Multidisciplinary comprehensive nursing intervention has a positive effect on alleviating skin itching severity, reducing the incidence of adverse skin events, and improving sleep quality in MHD patients with malignant tumors.

Objective To explore the correlation between serum phosphorylated Tau protein-181(P-Tau181),gamma glutamyl transpeptidase(GGT),silent information regulator 1(SIRT1)and sleep disorders in patients with cerebral small vessel disease.Methods A total of 156 patients with cerebral small vessel disease(CSVD)were divided into a sleep disorder group(PSQI≥10)and a normal sleep group(PSQI<10)based on the Pittsburgh Sleep Quality Index(PSQI)scores.Serum levels of P-Tau181,GGT,and SIRT1 were compared between the two groups,and the predictive value of these biomarkers for the development of sleep disorders in CSVD patients was analyzed.Results Among 156 patients with cerebral small vessel disease(CSVD),52(33.33%)were diag-nosed with sleep disorders,and their Pittsburgh Sleep Quality Index(PSQI)scores were significantly higher than those of the normal sleep group(P<0.05).The serum levels of P-Tau181,GGT,and SIRT1 in the sleep disorder group were elevated compared to the normal sleep group(P<0.05).Positive correlations were observed between PSQI scores and P-Tau181,GGT,and SIRT1 levels(P<0.05).The areas under the curve(AUC)for predicting sleep disorders in CSVD patients using individual biomarkers(P-Tau181,GGT,SIRT1)and their combined prediction were 0.672,0.742,0.749,and 0.843,respectively.Conclusion The abnormal expression of P-Tau181,GGT,and SIRT1 is associated with sleep disorders in patients with cerebral small vessel disease.

Objective To investigate the effects of Nel-like type 1 molecule(NELL-1)on the proliferation and osteogenic differenti-ation of stem cells from human exfoliated deciduous teeth(SHEDs).Methods SHEDs was isolated,cultured,and identified.The third generation SHEDs were used for subsequent experiments.SHEDs were divided into 4 groups,and NELL-1 was added to each group at concentrations of 0(control group),50,100,and 200 ng/mL.Cell activity was measured by CCK-8 assay and crystal violet staining.The changes in osteogenic ability were detected by alkaline phosphatase activity.The expression levels of osteogenesis-related genes ALP,OCN and Runx-2 by RT-qPCR were detected.Western blot was used to detect the expression of osteogenesis-related pro-teins ALP,Runx-2 and Col-Ⅰ.Results SHEDs exhibited stem cell characteristics,and 50 ng/mL of NELL-1 protein had a promo-ting effect on SHEDs proliferation(P＜0.01).Alkaline phosphatase activity assay showed that after the addition of NELL-1,the osteo-genic effect of each group was better than that of the control group and 50 ng/mL of NELL-1 was the best(P＜0.05).RT-qPCR and Western blot results showed that 50 ng/mL of NELL-1 significantly promoted the expression of osteoblast-related genes including ALP,OCN and Runx-2 and the protein expression of ALP,Runx-2 and Col-Ⅰ(P＜0.05).Conclusion NELL-1 can promote the prolifera-tion and osteogenic differentiation of SHEDs.

Heavy metals are common occupational hazards that can enter the human body through ingestion, skin contact, and inhalation, damaging various systems including the nervous system and causing a serious disease burden. Numerous studies have shown that heavy metal-induced neurotoxicity is closely linked to intestinal flora imbalance, with exposure to heavy metals leading to a reduction in the diversity of intestinal flora and a decrease in beneficial intestinal bacteria. Due to their few adverse reactions and significant health-regulating effects, probiotics and their formulations are widely used. Supplementing probiotics can alleviate heavy metal-induced neurotoxicity by modulating intestinal flora and their metabolites, reducing inflammation and oxidative stress, and adsorbing heavy metal ions to facilitate their excretion. This article takes four common heavy metals, namely lead, mercury, cadmium and manganese, as examples to review the role of intestinal flora imbalance in the neurotoxicity of heavy metals and the mechanism and application of probiotic intervention treatment, aiming to provide new ideas for the prevention and treatment of heavy metal neurotoxicity and explore the potential mechanism and application value of probiotic intervention.