Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

BACKGROUND:Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts.However,there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS:The human periodontal ligament stem cells were isolated and cultured.Passage 3 cells were selected and treated with ordinary medium containing different concentrations(0,1,2,4,6,8 μmol/L)of ursolic acid.After intervention for 1,3,5,7 days,the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened.Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0,1,2,4 μmol/L ursolic acid,respectively.After 7 days of intervention,the mRNA expressions of alkaline phosphatase,Runx2,and osteocalcin were detected by qRT-PCR.After 14 days of intervention,the formation of mineralized nodules was observed by alizarin red staining.Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution;the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid(2 μmol/L)and the bone morphogenetic protein signaling pathway antagonist Noggin,respectively.The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid(2 μmol/L)and Noggin,the inhibitor of bone morphogenetic protein signaling pathway,and cultured for 7 days.qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2. RESULTS AND CONCLUSION:(1)1,2,4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells.6,8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells,and 1,2,4 μmol/L ursolic acid was selected to intervene in subsequent experiments.(2)Compared with 0 μmol/L,1,2,4 μmol/L ursolic acid could promote the expression of alkaline phosphatase,Runx2,and osteocalcin mRNA and the formation of mineralized nodules(P<0.05),and the effect of 2 μmol/L ursolic acid was the most significant.(3)Compared with the control group,the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2 in the ursolic acid group were increased(P<0.05),while mRNA and protein expressions of the above indexes were decreased in the antagonist group(P<0.05).Compared with the ursolic acid group,mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group(P<0.05).(4)The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Objective To clarify the active ingredients and the potential molecular mechanism of Guben Qushi Huayu Prescription in treating psoriasis recurrence.Methods An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was applied to analyze the whole formula and the constituents absorbed into blood of Guben Qushi Huayu Prescription,and molecular docking technology was used to study the binding affinity of the constituents absorbed into blood with psoriasis-related immunomodulatory proteins such as CD69 and CD103 proteins.Results Mass spectrometry analysis identified 21 active ingredients such as paeoniflorin in Guben Qushi Huayu Prescription,including several known anti-inflammatory and immunomodulatory compounds.Analysis of the constituents absorbed into blood identified 11 ingredients,including paeoniflorin,that may affect the course of psoriasis through blood circulation.Molecular docking studies revealed that the constituents absorbed into blood,including astilbin,isoastilbin,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,helicine,paeoniflorin,ononin,all had high binding affinities with CD69 and CD103 proteins.Conclusion This research reveals the main active ingredients of Guben Qushi Huayu Prescription and their potential mechanism for regulating the recurrence of psoriasis by mass spectrometry and molecular docking technology,contributing to providing scientific basis for further pharmacological research and clinical application.

Ovarian cancer has the highest mortality rate in female malignant tumors of reproduc-tive system,with high recurrence rate and secondary resistance to platinum-containing chemotherapy.In recent years,adoptive cell immunotherapy(ACT),as an emerging immunotherapeutic strategy,shows great potential in the treatment of ovarian cancer.Although the immunosuppressive microenvironment and limited target selection are still the main challenges facing the current ACT treatment for ovarian cancer,it is still expected that the efficacy of ACT in ovarian cancer patients can be further improved by optimizing the cell production techniques and combining multiple thera-peutic approaches.This paper aims to provide a reference for the development of innovative thera-pies for ovarian cancer by reviewing the latest research progress on the mechanism and application of ACT therapy in ovarian cancer.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objective:To correlate serum bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) levels with joint function and systemic inflammatory response in patients with knee osteoarthritis (KOA) complicated by cartilage injury.Methods:This study is a retrospective analysis. It selected 258 patients with knee osteoarthritis who were treated at Yantai Yuhuangding Hospital from January 2022 to December 2023. All patients underwent arthroscopic examination. Based on the presence of cartilage injury, 118 patients with cartilage injury were included in the Group A, while 140 patients without cartilage injury were included in the Group B. Joint function (WOMAC Osteoarthritis Index, Lysholm Knee Function Score), serum levels of BMP-2 and COMP, and systemic inflammatory responses [levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α)] were compared between the two groups. Receiver Operating Characteristic (ROC) curves were drawn to analyze the diagnostic efficacy of serum BMP-2 and COMP levels for KOA complicated by cartilage injury. Pearson correlation analysis was used to assess the correlation between the aforementioned serum markers and the patients' WOMAC Osteoarthritis Index, Lysholm Knee Function Score, as well as serum levels of IL-1, IL-6, and TNF-α.Results:Group A had significantly lower serum BMP-2 levels and Lysholm Knee Function Scores compared with Group B [(9.18 ± 1.65) ng/L vs. (11.43 ± 2.51) ng/L, t = 8.34, P < 0.001; (80.06 ± 8.34) vs. (86.94 ± 7.21), t = 7.11, P < 0.001]. Group A exhibited higher serum levels of COMP, IL-1, IL-6, and TNF-α, as well as a higher WOMAC Osteoarthritis Index, with all differences being statistically significant [(6.88 ± 2.34) μg/L vs. (5.04 ± 1.01) μg/L, t = -8.34, P < 0.001; (43.18 ± 7.81) ng/L vs. (35.96 ± 5.02) ng/L, t = -8.96, P < 0.001; (34.03 ± 6.68) ng/L vs. (28.75 ± 5.61) ng/L, t = -6.90, P < 0.001; (13.17 ± 1.89) ng/L vs. (11.24 ± 1.01) ng/L, t = -10.44, P < 0.001; (137.18 ± 18.95) vs. (121.14 ± 13.58), t = -7.90, P < 0.001]. ROC curve analysis indicated that the area under the curve values for serum BMP-2 and COMP levels in diagnosing KOA complicated by cartilage injury were 0.773 and 0.811, respectively. Pearson correlation analysis revealed a negative correlation between serum BMP-2 levels and the WOMAC Osteoarthritis Index, as well as serum levels of IL-1, IL-6, and TNF-α ( r = -0.52, -0.42, -0.40, -0.57, all P < 0.05). Additionally, serum BMP-2 levels showed a positive correlation with the Lysholm Knee Function Score ( r = 0.51, P < 0.05). Serum COMP levels and the WOMAC Osteoarthritis Index were positively correlated with serum IL-1, IL-6, and TNF-α levels ( r = 0.48, 0.45, 0.37, 0.54, all P < 0.05) and were negatively correlated with the Lysholm Knee Function Score ( r = -0.51, P < 0.05). Conclusions:Serum BMP-2 and COMP levels have certain diagnostic value in patients with KOA complicated by cartilage injury. Moreover, these indicators are correlated with joint function and systemic inflammatory responses. Therefore, they hold promise as potential indicators for assessing disease progression in patients with KOA.