China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.
Animals ; Cell Differentiation/physiology* ; Cell Proliferation ; Mice ; Odontoblasts/metabolism* ; Odontogenesis ; Tooth Germ

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Regulation, Neoplastic ; In Situ Hybridization, Fluorescence ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Rats

PURPOSE: The house dust mite (HDM) is one of the most important sources of indoor allergens and a significant cause of allergic rhinitis and allergic asthma. Our previous studies demonstrated that Vibrio vulnificus flagellin B (FlaB) plus allergen as a co-treatment mixture improved lung function and inhibited eosinophilic airway inflammation through the Toll-like receptor 5 signaling pathway in an ovalbumin (OVA)- or HDM-induced mouse asthma model. In the present study, we fused the major mite allergen Derp2 to FlaB and compared the therapeutic effects of the Derp2-FlaB fusion protein with those of a mixture of Derp2 and FlaB in a Derp2-induced mouse asthma model. METHODS: BALB/c mice sensitized with Derp2 + HDM were treated with Derp2, a Derp2 plus FlaB (Derp2 + FlaB) mixture, or the Derp2-FlaB fusion protein 3 times at 1-week intervals. Seven days after the final treatment, the mice were challenged intranasally with Derp2, and airway responses and Derp2-specific immune responses were evaluated. RESULTS: The Derp2-FlaB fusion protein was significantly more efficacious in reducing airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE than the Derp2 + FlaB mixture. CONCLUSIONS: The Derp2-FlaB fusion protein showed a strong anti-asthma immunomodulatory capacity, leading to the prevention of airway inflammatory responses in a murine disease model through the inhibition of Th2 responses. These findings suggest that the Derp2-FlaB fusion protein would be a promising vaccine candidate for HDM-mediated allergic asthma therapy.
Allergens ; Animals ; Asthma ; Eosinophils ; Flagellin ; Immunoglobulin E ; Inflammation ; Lung ; Mice ; Mites ; Ovalbumin ; Pyroglyphidae ; Rhinitis, Allergic ; Therapeutic Uses ; Toll-Like Receptor 5 ; Vibrio vulnificus

Aim To assess the effects of Banqiao Codonopisis Pilosula(BCP)decoction on learning and memory dysfunction in AD model rats induced by high activity GSK-3β and its possible mechanism.Methods The SD rats(4 months old,♂)were divided into five groups,namely,sham-operated group(blank group),AD model group,BCP high-dose(2.16 g·kg-1·d-1)group,BCP medium-dose(1.08 g·kg-1·d-1)group,and BCP lower-dose(0.54 g·kg-1·d-1)group.Treatment group received BCP decoction by gavage once a day for 14 days,while other groups were offered drinking water by gavage once a day for 14 days.The autonomous behavior activities of all rats were observed and recorded after gavage.In the last seven days by gavage,Morris water maze test was used to test the spatial learning and memory ability of the five groups.After five days training,treatment groups and AD model group were injected wortmannin(WT,PI3K specific inhibitor)and GF-109203X(GFX,PKC specific inhibitor)(100 μmol·L-1 of each,total volume of 10 μL)into the right lateral ventricle of the rats.The blank group was only injected 2％DMSO.The spatial memory retention was detected by water maze 24 hours after lateral ventricle injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of related protein kinase GSK-3β were detected by Western blot and immunohistochemistry.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl′s staining.Results After intragastric administration of BCP,the rat autonomous behavior activities in each group all showed a declining trend,and the differences in low-dose and middle-dose groups had statistical significance compared with blank group.The Morris water maze tests showed that the latency navigation of model group was significantly longer than that of blank group(P<0.01),while that of the BCP three doses groups was shorter than that of model group(P<0.05).Compared with the same group,the latency navigation of the three groups after gavage BCP low,middle and high dose was significant shorter than that without gavage(P<0.05).Western blot results showed that the activity of GSK-3β in AD model group was up-regulated compared with the blank group.However,BCP inhibited activity of GSK-3β.Western blot and immunohistochemistry results showed the level of Tau phosphorylation in AD model group was increased compared with the blank group in the area of CA3(P<0.05).Compared with AD model group,the level of Tau phosphorylation was decreased in treatment group.Nissl′s staining results showed that dendritic spines in AD model group was significantly attenuated compared with the blank group(P<0.05).Far more dendritic spines were observed in treatment group than in AD model group.The number of Nissl′s bodies in neuron cells of hippocampus in hippocampal CA3 was obviously larger in treatment groups than in AD model group.These effect of BCP was dose-dependent.Conclusions BCP can prevent the learning and memory dysfunction in AD model rats induced by high activity of GSK-3β.The mechanism may be related to inhibiting GSK-3β activity and then reducing the level of phosphorylation of Tau and improving neural development.

Objective To explore the Kano model analysis in the application of midwife outpatient service quality management. Methods Kano questionnaire was consisted of 24 items, including five parts, environment facilities, service evaluation, service technology, the team service, delivery service′quality. Using the Kano model analysis, the impact factors of the midwife outpatient service quality in five different quality attributes were determined. It included property and had the opposite answer to the question, charisma, essential properties and one property. Results By identifing the quality index classification of the pregnant women with satisfactory service quality to midwife outpatient service, attributable to a property were 1,2,3,4,8,9,10,14,20,21;attributable to mandatory attributes were 13, belonging to the charm of the property had 5,6,7,11,12,15,16,17,18,19,22,23,24. Midwives outpatient had most of charisma attribute, 54.2%(13/24) of the total;The second was one attribute, 41.7% (10/24) of the total. The technology level of midwife was essential attribute. Conclusions Kano mode analysis technology will be introduced to the midwife outpatient service quality management to provide decision reference for improving the quality of the hospital management level, improve maternal satisfaction, improve the obstetric operation efficiency.

Objective To evaluate the effect of JY adjuvant,which is composed of IL-2 and chitosan,on the immune response for mucosal immunization with human papillomavirus types 16 and 18 L1 virus-like particles (HPV16 + 18 L1 VLP).Methods Mice were immunized three times with HPV16 + 18 L1 VLP in the presence or absence of JY adjuvant by intramuscular and intranasal routes,respectively.Subsequently,experiments were undertaken to detect serum IgG antibody,neutralizing antibody and respiratory tract washes sIgA antibody titers and cellular immune response.Results Following intranasal immunization,serum IgG antibody titers were much higher in HPV16 + 18 L1 VLP with JY adjuvant group than that in VLP without adjuvant group (P ＜ 0.01),after intramuscular immunization,serum IgG titers induced by VLP with or without JY adjuvant were the same; following intramuscular immunization,neutralizing antibody titers induced by adjuvant-containing HPV16 + 18 L1 VLP were higher than those by adjuvant-free VLP,following intranasal immunization,only serum neutralizing antibody was detected in adjuvant-containing VLP group; after intranasal immunization,lung washes sIgA concentration were much higher in HPV16 + 18 L1 VLP with JY adjuvant group than that in VLP without adjuvant group (P ＜ 0.05) ; following intranasal and intramuscular immunization,respectively,the number of spot forming cells were much higher in HPV16 + 18 L1 VLP with JY adjuvant group than that in VLP without adjuvant group (P ＜ 0.01,P ＜ 0.05,respectively).Conclusion JY adjuvant enhanced the cellular,humoral and mocosal immunities induced with HPV16 + 18 L1 VLP by intranasal route,while showed no significant influence of the adjuvant was seen in the group immunized by intramuscular route.

Objective We develop a rapid,specific,sensitive tandardized SOP.And initial application for 200 nasopharyngeal aspirates of children with related pathogens of acute respiratory tract infections in BeiJing area.Methods To developed nested PCR and TaqMan probe real-time fluorescence quantitative PCR method for detection of KIPyV and WUPyV'S gene,and then the sequences of gene fragments are analyzed.Evalution of two assays from 200 nasopharyngeal aspirates.Results In this study,sensitivity of TaqMan probe real time fluorescent quantitative PCR assay was higher than one of nested PCR (500 copies/μl),and both assays did not show any positive amplification in detetion of other respiratory virus.Coefficient of varience of KIPyV and WUPyV are less than 2.9％ and 1.95％ respectively in the repeatability detection.The detection rates of KIPyV,and WUPyV were 1.5％ and 8％ in nested PCR assay and 12％ and 14％ in real time Fluorescent quantitative PCR assay respectively.Conclusion This study established good sensitivity and reproducibility,high specificity and rapid method for detection nucleic acid of these polyomaviruses that have good prospects on the clinical application.

Objective To investigate the effects and mechanisms of sorafenib on hepatic stellate cell viability and activation in the microenvironment of liver tumor.Methods The effects of LX2 cells on HepG2 cell proliferation were observed by coculture of LX2 and HepG2 cells.MTT assay was used to observe the effects of sorafenib on LX2 proliferation,and expression of α-smooth muscle actin (α-SMA) was measured immunocytochemically in LX2 cells treated with different concentrations of sorafenib.Changes in PDGF-BB and TGF-β1 concentrations were detected in LX2 supernatant using ELISA.Expression of ERK1,ERK2,and AKT signaling pathways were measured using Western blot.Furthermore,LX2 cells were cocultured with HepG2 cells for 24 hours to observe their effects on the invasive ability of HepG2 cells.Result After coculture of LX2 and HepG2 cells,HepG2 cells increased in the experimental group more than those of in the control group.After treatment with various concentrations of sorafenib for 12,24,36 or 48 hours,the viability of treated LX2 cells was lower than the controls in a concentration-and time-dependent manner.As sorafenib concentration and time of exposure increased,α-SMA expression became weaker in treated cells.PDGF-BB and TGF-β1 concentrations decreased with higher sorafenib concentrations and with longer exposure under the same concentration.ERK1,ERK2 and Akt expression was identical between treated and control groups,but their phosphorylated expression decreased with increased concentrations of sorafenib.The invasive ability of HepG2 cells induced by LX2 gradually decreased as sorafenib concentrations increased.Conclusions Sorafenib suppressed α-SMA expression,inhibited PDGF-dependent signaling pathways in HSCs,downregulated PDGF-BB and TGF β1 expression in the supernatant of HSCs,and restrained the viability and activation of HSCs.Sorafenib treatment therefore resulted in suppressed proliferation and invasion of HepG2 cells.