The research on artificial womb technology and “fetus and newborn” by Deby et al.， as well as the Food and Drug Administration’s discussion on whether the world’s first human clinical trial of “artificial womb” technology should be approved， have sparked a new wave of research on artificial womb technology. By extending and deepening relevant foreign research， the three potential application prospects of artificial womb technology were clarified， including rescuing extremely preterm infants， reducing the burden of pregnancy， and assisting advanced maternal age. The ethical risks it faced were pointed out， encompassing the moral status of the gestational entity was questionable， and the risks of technological experimentation could not be quantified. The governance pathways were clarified， involving multi-layered ethical considerations to complete the clear identification of the gestational entity’s identity， and multi-faceted patient-doctor consultations to achieve clear risk notification. Through discussions on the application prospects， ethical risks， and governance pathways of artificial womb technology can improve human welfare and realize the technology for human use.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

ObjectiveTo investigate the relationship of physical activity (PA) and cognitive function to sleep quality in older adults with cognitive impairment based on resting electroencephalogram (EEG), and to explore the mediating role of specific EEG markers in the relationship between PA and sleep quality. MethodsFrom March to May, 2024, 137 older adults were recruited from Chenfu Jiayuan and Qiangwei Jiuli in Songjiang district, and Luyan communities in Jinshan district, Shanghai. The assessments included Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Pittsburgh Sleep Quality Index (PSQI), along with a five-minute EEG recording. ResultsThere was significant difference in sleep quality among older adults with different levels of cognitive impairment (t = -7.400, P < 0.001). The PSQI total score was negatively correlated with MoCA scores (r = -0.412, P < 0.001) and total physical activity level (PAL) (r = -0.363, P < 0.001). The θ power in the frontal areas (F3, F4) was significantly correlated with both PSQI scores and PAL (P < 0.01). The θ power in F3 + F4 exhibited a significant partial (effect size = -0.0004, 95%CI -0.0007 to -0.0002) mediating effect between PA and sleep quality in older adults with cognitive impairment. ConclusionOlder adults with more severe cognitive impairment tend to have poorer sleep quality, whereas higher PAL is associated with better sleep quality. PA can indirectly influence sleep quality in older adults with cognitive impairment by affecting θ power (F3 + F4).

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Objective To investigate the correlation between muscle strength level and bone mineral density and bone metabolism indexes in postmenopausal women in Beijing.Methods Postmenopausal women who were investi-gated by on-site questionnaires and followed by bone mineral density examination in Beijing from September 2017 to May 2018 were recruited as study subjects.They were divided into early menopausal group,middle menopausal group,late menopausal group,and twilight menopausal group according to the years of menopause.Changes in grip strength,5 times sit-to-stand test(FTSST)with bone mineral density(BMD)and bone metabolism indexes were observed in the four groups and their correlations were analyzed.Results A total of 815 cases of postmenopausal women were included.At different menopausal stages,muscle strength was all found to decrease with the increase of menopausal years(P＜0.05),there was non-significance of different bone metabolism indexes among the four groups(P＞0.05);Femoral neck and lumbar spine BMD decreased with the increase of menopausal years(P＜0.05).Maximum grip strength was positively correlated with both femoral neck and lumbar spine BMD(R=0.158,P＜0.05;R=0.130,P＜0.05).There was no correlation between muscle strength and bone metabo-lism indexes(P＜0.05).Conclusions Different bone metabolism indexes are not associated with muscle strength in menopausal women.Maximum grip strength is positively correlated with bone mineral density,which can be used as an auxiliary screening tool for osteoporosis(OP)in women.The FTSST suggests that the lower limb muscle strength of menopausal women decreases with age,which can be used as one of the indicators for predicting the risk of falls in menopausal women.

Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15(CASC15),a long-stranded non-coding RNA(lncRNA),in hepatocellular carcinoma(HCC).Methods Bioinformat-ics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Tr-answell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1(LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression.Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells(P<0.05).The results of cell function experiments on proliferation,inva-sion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibi-tory effect,consistent with the results of apoptosis experiments(P<0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby pro-moting HCC cell proliferation,invasion and migration,and inhibiting apoptosis.Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Objective To investigate effects of ligustilide(LIG)on proliferation,apoptosis,angiogenic mimicry and Ras homolog gene family member A(RhoA)/Rho associated coiled coil containing protein kinase 1(ROCK)signaling pathway in esophageal cancer cells.Methods Esophageal cancer cell line EC-109 was treated with LIG at concentrations of 0,12.5,25,50,100,and 200 μmol/L to detect cell activity,and the suitable concentration was selected for subsequent experiments.EC-109 cells were grouped into the control group,the LIG low,medium and high concentration groups(LIG-L,LIG-M and LIG-H groups),and the LIG-H+RhoA activator Naciclassine group(LIG-H+Naciclassine group).Edu was applied to detect cell proliferation,and flow cytometry was applied to detect cell apoptosis.Angiogenetic mimicry was observed.Western blot assay was applied to detect expression levels of proteins related to cell proliferation and apoptosis,and RhoA,ROCK proteins.Nude mouse tumor transplantation experiment was applied to verify the effect of LIG on the growth of esophageal cancer tumors.Immunohistochemistry was applied to detect expression levels of angiogenesis related factors(VEGF),RhoA and ROCK proteins in transplanted tumors.Results Compared with the control group,the vascular mimicry tubular structure of EC-109 cells decreased sequentially in the LIG-L group,the LIG-M group and the LIG-H group.The positive rate of Edu,the expression levels of Cyclin D1,Ki67,Bcl-2,RhoA and ROCK reduced in turn.P21,cell apoptosis rate,the expression of Bax and Caspase-3 increased in sequence(P＜0.05).Naciclasine,RhoA activator,partially reversed the effect of LIG on cell proliferation,apoptosis and vasculogenic mimicry of esophageal cancer cells.Nude mouse transplantation tumor experiment showed that compared with the control group,the growth rate of transplanted tumor showed down,tumor volume decreased and the expression levels of RhoA,ROCK and VEGF decreased in the LIG group(P＜0.05).Conclusion Ligustilide inhibits the proliferation and angiogenic mimicry of esophageal cancer cells by inhibiting RhoA/ROCK signaling pathway,and promotes the apoptosis of esophageal cancer cells.

Objective:To investigate diagnostic and prognostic value of actin-binding protein ANLN in clear cell renal cell carcinoma(ccRCC)and its relationship with tumor microenvironment.Methods:Gene expression data and clinical data for ccRCC were downloaded from The Cancer Genome Atlas(TCGA).Relationship between ANLN expression and clinicopathological features was assessed by Wilcoxon rank sum test and Logistic regression.Receiver operating characteristic(ROC)curve was used to assess diagnostic value of ANLN expression in ccRCC.Kaplan-Meier and Cox regression analysis were used to investigate effect of ANLN expression on overall survival.Gene set enrichment analysis(GSEA)was used to identify signaling pathways associated with ANLN in ccRCC.Relationship between ANLN expression and immune infiltration was analyzed by ESTIMATE algorithm,tumor immune estima-tion resource(TIMER)and CIBERSORT algorithms.Relationship between ANLN and drug sensitivity was calculated using CellMiner database.Results:ANLN expression was significantly upregulated in ccRCC tissues.ANLN expression in ccRCC was correlated with clinicopathological features.ROC analysis showed that ANLN had a high diagnostic value in ccRCC.High ANLN expression was signifi-cantly associated with poor prognosis.Multivariate Cox regression analysis showed that high ANLN expression was an independent risk factor for overall survival in ccRCC patients.GSEA showed that ANLN was associated with multiple signaling pathways.In terms of immunity,ANLN was closely associated with tumor microenvironment,immune infiltration and immune checkpoint molecules in ccRCC.ANLN expression was negatively correlated with sensitivity of most antitumor drugs.Conclusion:ANLN is a potential diagnos-tic and prognostic biomarker and immunotherapeutic target for ccRCC.