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.

Objective To investigate the the levels of magnesium,lead,iron,zinc,copper,manganese,calci-um in whole blood in children aged 0-12 years in Henan province,understand the health status of children and provide a basis for their nutrition and health management.Methods Data were collected from totally 135 385 children aged 0-12 years who underwent trace element testing at Zhengzhou Kingmed Clinical Labo-ratory Inc.from 2019 to 2023 were selected,and agilent inductively coupled plasma mass spectrometer was used to detect seven elements(magnesium,lead,iron,zinc,copper,manganese,and calcium).The elemental detection method in the laboratory has been strictly methodologically verified,and has participated in the ex-ternal quality assessment organized by National Center for Clinical Laboratories.Grouping was conducted based on gender,age,season,region,and year to compare the deficiencies and lead exceedances of six elements(magnesium,iron,zinc,copper,manganese,calcium)under different conditions.Results In this study,the mean P-values of seven elements in different age groups,gender groups,year groups,and regional groups were all＜0.001.Except for lead with a P-value of 0.002,all other elements in different season groups were＜0.001.The P-values were all less than 0.05,indicating statistically significant differences.Among them,Mag-nesium,iron,and zinc in children's whole blood showed an increasing trend with age,while copper,manga-nese,and calcium showed a decreasing trend with age.The proportions of children aged 0-1 years with iron,zinc,and manganese deficiencies were the highest,at 24.70％,48.20％,and 0.65％,respectively.The highest proportion of copper and calcium deficiency was in the age range of 11-12 years old,accounting for 20.43％and 0.17％respectively.The highest proportion of lead exceeding the standard was 0.87％among children aged 0-1.Except for manganese and calcium levels,the levels of the other five elements were higher in boys than in girls.Magnesium and copper levels were highest in spring,iron,zinc,and calcium levels were highest in winter,and manganese and lead levels were highest in summer.Magnesium deficiency,calcium deficiency,and lead excess were showing a decreasing trend year by year.Among them,the lead levels of children in Sanme-nxia and Jiyuan were relatively high compared to other areas.Conclusion 0-2 years children are mainly char-acterized by calcium and zinc deficiency in Henan province.Attention should be paid to iron and zinc supple-mentation in infants and young children.At the same time,it should also be noted that the deficiency rate of copper increases with age,and attention should be paid to the supplementation of copper in children.

Objective To evaluate the efficacy of transcatheter arterial chemoembolization(TACE)combined with argon-helium cryoablation(AHC)in the treatment of hypervascular small hepatocellular carcinoma(sHCC).Methods The clinical data of 35 patients with hypervascular sHCC,who received TACE combined with AHC at the Affiliated Cancer Hospital of Zhengzhou University of China from March 2018 to February 2019,were retrospectively analyzed.All patients were treated with TACE treatment first,after 3-7 days the patients received AHC therapy.The postoperative 1-,3-,and 6-month curative effect were evaluated,and the postoperative 1-,3-,and 5-year survival rates were calculated.The liver function and immune function indicators,as well as the serum tumor markers were detected.The adverse reactions during treatment were recorded.Results The postoperative 1-,3-,and 6-month objective remission rate(ORR)were 100.00％,94.29％and 91.43％respectively,and the disease control rate(DCR)were 100.00％,100.00％and 97.14％ respectively.The overall survival(OS)was(46.54±2.88)months,and the postoperative 1-,3-,and 5-year survival rates were 94.29％(33/35),65.71％(23/35)and 48.57％(17/35)respectively.The postoperative 3-day serum levels of ALT,AST and TBIL were significantly elevated when compared with their preoperative baseline levels(all P＜0.05),which returned to preoperative levels in 2 weeks after treatment(P＞0.05).The postoperative 2-week CD4+％and CD4+％/CD8+％ratio were remarkably increased when compared with their preoperative values(both P＜0.05),while the postoperative 2-week AFP,AFP-L3％,DCP and GPC3 levels were strikingly decreased when compared with their preoperative values(all P＜0.001).None of the patients developed procedure-related severe complications after treatment.Conclusion For the treatment of hypervascular sHCC,TACE combined with AHC has satisfactory clinical efficacy and safety.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 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 Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated 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 thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

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.

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 effect of Galangin on pyroptosis of bone marrow derived macrophages(BMDMs).Methods BMDMs were cultured in vitro and divided into blank control group,model group and Galangin group with different concentrations.Lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were used to construct the pyroptosis model.The effect of different concentrations of Galangin on the proliferation of BMDMs was detected by cell counting Kit-8(CCK-8).The level of cysteinyl aspartate specific proteinase-1 p10 subunit(caspase-1 p10),interleukin-1β(IL-1β)in supernatant and intracellular nucleotide NOD-like receptor protein 3(NLRP3)were detected by Western blotting.IL-1β in supernatant was detected by enzyme-linked immunosorbent assay(ELISA).The cell death was observed by propidium iodide(PI)staining.High-throughput sequencing was used to compare the gene expression in the model group and Galangin groups at 20 μmol/L.Results There was no statistically significant difference between the 5,10,20,40,60,80 μmol/L Galangin groups on the proliferation level of BMDMs(all P>0.05),indicating that no significant effect of Galangin at 5,10,20,40,60,80 μmol/L was observed on the proliferation of BMDMs.So we selected Galangin at 5,10,20 μmol/L and treatment for 1,2 and 4 hours as the effects of different concentrations and time on the pyroptosis of BMDMs.Compared with blank control group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant in model group were significantly increased(all P<0.05).Compared with model group,the expression of caspase-1 p10 and mature IL-1β protein and IL-1β in supernatant of Galangin at 5,10 and 20 μmol/L were significantly decreased[IL-1β protein expression(gray value):0.155±0.006,0.113±0.006,0.111±0.007 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.207±0.044,0.160±0.008,0.082±0.008 vs.1.000±0.000,IL-1β(μg/L):99.80±10.36,85.21±8.78,26.53±4.56 vs.494.10±35.47,all P<0.05].There was no significant difference between the different concentration groups(all P>0.05),but with the extension of treatment time of Galangin,the inhibitory effect was enhanced.The inhibitory effect of Galangin at 20 μmol/L for 4 hours was the most obvious[IL-1β protein expression(gray value):0.186±0.004 vs.1.000±0.000,caspase-1 p10 protein expression(gray value):0.247±0.009 vs.1.000±0.000,IL-1β(μg/L):173.80±10.56 vs.653.80±76.02,all P<0.05].Treatment with 20 μmol/L Galangin for 4 hours could reduce the number of pyroptotic cell deaths(number of view:23.00±3.61 vs.67.67±15.63,P<0.05)and inhibited the expression of NLRP3 protein(gray value:0.178±0.025 vs.0.406±0.066,P<0.05).High-throughput sequencing showed that,compared with the model group,Galangin down-regulated the genes of Nlrp3,Nod2,IL-1β and up-regulated genes of Skp2(also known as Fbxl1),Fbxl20,Fbxl4,Fbxo32 and Fbxw7.Conclusion Galangin inhibited pyroptosis mediated by NLRP3 inflammasome in macrophages.