Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective:To analyze the registration status of clinical trials related to contraceptives based on the data of World Health Organization International Clinical Trials Registry Platform (ICTRP), so as to understand the situation of contraceptives development, and provide reference for improving the quality of clinical trials.Methods:All records in the database of ICTRP before January 1, 2025 was researched to screen out contraceptives clinical trials, and the registration time, registration platform, regional distribution, trial design and research content were analyzed.Results:A total of 206 clinical trials related to contraceptives were included. The projects were mainly carried out in the United States, Germany, and India. About 95.63% (197/206) of the study subjects were women of reproductive age. The　main　type　of　study　was　intervention [89.32% (184/206)], among which random trials accounted for 53.26% (98/184), and parallel group trials were the most common [82.65% (81/98)]. Over 64.56% (133/206) of the trials were indicated with open-label. Most of the clinical trials were in phase Ⅲ [47.57% (98/206)] and phase Ⅳ [16.50% (34/206)]. The interventions in female studies were mainly in three aspects: oral contraceptive [42.64% (84/197)], intrauterine delivery [15.23% (30/197)], and vaginal delivery [15.23% (30/197)], and the primary outcome included pregnancy rate [54.82% (108/197)], adverse drug reactions [13.20% (26/197)], ovulation inhibition [8.63% (17/197)], and vaginal infection [4.06% (8/197)].Conclusion:The　clinical　trials　of contraceptives were unevenly distributed, the research types were mainly randomized interventional trials, the included participants were mainly women of reproductive age, the intervention measures were mostly oral contraceptive, intrauterine delivery and vaginal delivery.

When the epidemiology of infectious diseases is more complex, it is often difficult for disease prediction studies based on a single model to capture the multidimensional nature of disease transmission. In recent years, combining different models to improve infectious disease prediction has gradually become a research trend and hotspot. Existing studies have shown that combined models usually have higher prediction performance and better generalization ability. The current combined models mainly combine machine learning and other models, including time-series models, dynamic models, etcetera. In addition, integrated learning that combines diverse machine learning techniques also holds significant importance across various research domains. This paper reviews the progress of applying combined models around machine learning in infectious disease prediction to promote the innovation and practice of combined models for infectious diseases and help to build smarter and more efficient infectious disease early warning and prediction methods and systems.

Methods such as compartmental models, agent-based models, time series models, and machine learning can be used for the prediction of infectious disease incidence. When disease epidemics are complex, it is often difficult to use a single model to comprehensively and accurately capture the multi dimensional nature of the disease. Exploring the combined application of different models has gradually become a research trend and hotspot in recent years, and the prediction performance of combined models is often better than that of single ones. Current research related to combined models mainly focus on machine learning or compartmental models. In this review, we focus on the combination of compartmental models and other models, and summarize their combination principles, application progress, and advantages or disadvantages for the purpose of promoting the innovation and application of combined models for infectious disease incidence prediction, and establishing a more intelligent and efficient early warning and prediction method or systems for the prevention and control of infectious disease.

Objective:To investigate the risk factors and prognosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis following herpes simplex virus encephalitis (HSE) in children.Methods:A retrospective cohort study was conducted on 83 children with HSE hospitalized at Beijing Children′s Hospital, Capital Medical University, from January 2013 to June 2023. The clinical data, including demographics, clinical manifestations, Glasgow coma scale (GCS) scores, auxiliary examinations, and treatment regimens, were collected. The prognoses of these children were evaluated using the modified Rankin scale (mRS), pediatric cerebral performance category (PCPC) scale, and pediatric quality of life inventory (PedsQL). These children were divided into 2 groups: those who developed secondary anti-NMDAR encephalitis and those who did not. Non-parametric tests were used for intergroup comparisons, and Logistic regression models were applied to identify risk factors for secondary anti-NMDAR encephalitis.Results:Among the 83 children with HSE, 23 children developed secondary anti-NMDAR encephalitis. The secondary anti-NMDAR encephalitis group exhibited a later age of onset compared to the non-secondary group (4.0 (2.2, 7.1) vs. 1.6 (0.8, 5.4) years, Z=2.19, P=0.028), lower GCS scores (8.0 (5.5, 11.5) vs. 14.0 (9.8, 15.0) points, Z=3.74, P<0.001), and worse prognostic outcomes as measured by mRS, PCPC scale and PedsQL (3.0 (2.0, 5.0) vs. 1.0 (0.3, 3.0) points, 3.0 (2.0, 4.0) vs. 2.0 (1.0, 4.0) points, 52.0 (17.0, 67.0) vs. 86.5 (53.3, 97.5) points, Z=3.48, 3.36, 3.09, all P<0.01). Logistic regression analysis identified lower GCS scores during HSE as an independent risk factor for the secondary anti-NMDAR encephalitis ( OR=0.82, 95% CI 0.72-0.94, P=0.003). Conclusion:For the children with HSE who present low GCS scores, regular follow-ups are imperative in order to monitor for the potential development of anti-NMDAR encephalitis, thus facilitating early intervention and improving clinical outcomes.