Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.

Objective To investigate prevalence and immunological properties of Helicobacter pylori (Hp) infection among chronic gastritis population in Wuhan. Methods A total of 1 866 patients with chronic gastritis in Wuhan were selected from May 2021 to December 2023, and Hp antibody and typing in serum were detected by immunoblotting to analyse the infection rate and typing of patients of different genders and age groups, as well as the correlation between Hp infection and the severity of chronic gastritis. Western blotting technique was utilized to detect the Hp antibodies and typing. The infection rates and subtypes were recorded in patients of different genders and ages. Then the correlation between Hp infection and the severity of chronic gastritis were discussed. Results The overall detection rate of Hp infection was 65.38% (1 220/1 866) in 1866 patients, and the prevalence rate of type I infection was higher than that of type II infection [61.31% (748/1 220) vs 38.69% (472/1 220), P<0.05]. No statistical difference was reported in overall infection rate in terms of gender (P>0.05). In terms of gender, the rate of type I infection was higher than that of type II infection [70.08% (431/615) vs 29.92% (184/615), P<0.05], whereas the prevalence of the two types of infections demonstrated no statistical difference in female patients (P>0.05). In terms of age, the prevalence of Hp infection in patients increased with age (2=64.687, P=0.000). The infection rate of type I was higher than type II in the age groups of below 18, 31-40, 41-50 and 51-60 years old (P<0.05), and infection rates of type I and type II yielded no statistical difference in the age groups of 18-30 and ≥60 years old (P>0.05). With the aggravation of chronic gastritis, the infection rate and percentage of type I infections increased, and the percentage of type I infections was higher than that of type II infections (P<0.05). Conclusion Patients with chronic gastritis in Wuhan suffer a high prevalence rate of Hp infection, and the rate of Hp infection increases with the age of the patients, is positively correlated with the severity of the disease, and presents certain typological features.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Objective To study the effect of curcumin on osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)in high glucose condition and its mechanism.Methods The cultured hBMSCs were divided into the normal group,high glucose group,and high glucose+curcumin group.The early osteogenic differentiation level of the cells in each group was assessed by detecting alkaline phosphatase(ALP)activity.Alizarin red staining was used to evaluate the formation of mineralized nodules in the late stage of osteo-genic differentiation.The expression of osteogenic-related genes,including Runt-related transcription factor 2(Runx2),osteocalcin(OCN),and type Ⅰ collagen(COL-1),was detected by RT-PCR after 21 days of osteogenic induction.Western blot was used to detect the expression of heme oxygenase-1(HO-1)in each group.Furthermore,an HO-1 small interfering RNA(siRNA)model was constructed and its interference efficiency was assessed.The expression levels of osteogenesis-related proteins(Runx2,OCN,and COL-1)between the high glucose+curcumin group and high glucose+curcumin+siHO-1 group were compared.Results Compared with the normal group,the high glucose group showed decreased ALP activity,reduced formation of mineralized nodules,decreased expression of osteogenic-related genes(Runx2,OCN,and COL-1),and inhibited expression of HO-1(P＜0.05).Compared with the empty vector group,the siHO-1 group showed significantly reduced expression of HO-1 in cells,indicating successful siRNA interference(P＜0.01).Compared with the high glucose+curcumin group,the expression levels of osteogenesis-related proteins(OCN,COL-1,and Runx2)were all decreased in the high glucose+curcumin+siHO-1 group(P＜0.05).Conclusion Curcumin can promote osteogenic differentiation of hBMSCs under high glucose environment,which is related to the expression of HO-1.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.