Perinatal depression (PND) is a critical public health issue affecting maternal and offspring health. Digital health intervention platforms, leveraging advantages in accessibility, privacy, and cost-effectiveness, demonstrate good application in PND prevention and treatment. This review systematically searched literature and policy documents published between January 2018 and March 2025 in CNKI, PubMed, Web of Science and World Health Organization. It summarized the development trajectory of digital health intervention platforms and their current applications and effectiveness in PND prevention and treatment. Existing evidence was evaluated across dimensions of efficacy, systematicity, and practicality, identifying major challenges faced by these platforms. Studies indicate that while PND digital health intervention platforms have achieved preliminary success in alleviating PND symptoms, widespread issues persist, including incomplete service closed-loop systems, low user adherence, and insufficient sustainability. Future efforts should focus on optimizing intervention content and interactive design, advancing intelligent assessment and tiered intervention strategies, strengthening continuous monitoring and crisis response mechanisms, and constructing a multidisciplinary collaborative support system. These steps are essential for achieving efficient, intelligent, and sustainable development of digital health intervention platforms for PND.

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Aim To evaluate the effect of ricolinostat on X-ray induced myocardial fibrosis and damage to primary cilia in myocardial fibroblasts.Methods Wistar rats were subjected to a single dose of 8 Gy whole-body irradiation,followed by intraperitoneal in-jection of ricolinostat.Serum troponinT(TnT)and brain natriuretic peptide(BNP)levels were measured using ELISA.The degree of myocardial tissue fibrosis was measured using HE and Masson staining.Type Ⅰcollagen and primary cilia were detected using immuno-fluorescence.The gene and protein levels of histone deacetylase 6(HDAC6)in myocardial tissue and cells were detected using PCR and Western blot.Results Compared with the control group,X-ray radiation in-creased type Ⅰ collagen content and promoted the pro-liferation of myocardial fibroblasts in rat myocardial tis-sue.X-ray radiation slightly up-regulated the expres-sion of HDAC6 in myocardial fibroblasts(P＞0.05),and significantly increased the formation of primary cil-ia in myocardial tissue and myocardial fibroblasts.Af-ter treatment with ricolinostat,the expression of HDAC6 and primary cilia formation decreased in myo-cardial tissue and myocardial fibroblasts(P＜0.05),and acetylation in the cytoplasm significantly in-creased.The arrangement of collagen fibers in myocar-dial tissue was slightly neat,collagen volume fraction was reduced,and the levels of TnT(P＜0.01)and BNP decreased.Conclusions Ricolinostat can miti-gate X-ray induced myocardial fibrosis via the disas-sembly of primary cilia,with potential value for trea-ting radiation-induced myocardial fibrosis.

Objective:To explore the relationship between the ultrasound parameters of reproductive system and the expression of endocrine hormone in female pediatric patients with precocious puberty(PP),and to assess the treatment effect.Methods:A total of 160 female pediatric patients with PP who admitted to Beijing Jingmei Group General Hospital from January 2021 to December 2021 were selected,and they were divided into a positive group and a normal group based on the diagnostic criteria for precocious puberty,with 80 cases in each group.Ultrasound examination was performed on the uterus,ovaries and breasts of 160 female pediatric patients with PP,and the relevant parameters of them were measured,and the levels of endocrine hormone in the serums of them were detected.The pediatric patients of positive group underwent again the ultrasound examination and the detection of endocrine hormone after they completed treatment.The differences of ultrasound parameters and endocrine hormone between two groups were compared,and the correlation of ultrasound parameters and endocrine hormone between two groups were analyzed,as well as the influence factors of treatment effect.Results:The length and thickness of the uterus,the ratio of the length of the uterus to the length of cervix,the thickness of the endometrium,the size of the ovaries,the number of follicles,and the width and thickness of the hypoechoic area of the breast in the positive group were significantly larger than them in the normal group,and the differences of them were statistical significance(t=16.8,12.6,12.4,14.7,11.5,15.8,10.9,10.2,P<0.05),respectively.The resistance index(RI)of uterine artery of positive group was significantly smaller than that of normal group,and the difference was statistically significant(t=-7.9,P<0.05).The serum estradiol(E2),gonadotropin(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),progesterone(P)and growth hormone(GH)levels of positive group were significantly higher than those of normal group,and the differences of them were significant(t=20.6,19.8,15.4,17.6,15.2,8.9,P<0.05),respectively.After treatment,the above-mentioned ultrasound parameters and endocrine hormone levels of the pediatric patients in the positive group were significantly improved.The relevant analysis showed that ultrasound parameters were positively correlated with levels of endocrine hormone,and they were important influence factor on the levels of endocrine hormone.In addition,the treatment effect was related to ultrasound parameters(OR=0.78-1.28,P<0.05),the levels of endocrine hormone(OR=0.73-0.77,P<0.05),age,height,weight and BMI(OR=0.70-0.72,P<0.05).Conclusion:The ultrasound parameters of the reproductive system of female pediatric patients with PP are closely related to the expression of endocrine hormones.The levels of endocrine hormones can be used as important indicators of the disease condition and prognosis of female pediatric patients with PP.