Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

BACKGROUND:Small diameter artificial vessels are urgently needed to treat coronary artery and peripheral artery diseases in clinical practice.At present,vascular tissue engineering has become the main method for preparing small diameter artificial vessels.Selecting suitable biomaterials and cell sources is the key factor for successful construction of small diameter tissue engineered vessels. OBJECTIVE:To observe the effect of four kinds of electrospinning membrane materials on proliferation,adhesion and differentiation of bone marrow mesenchymal stem cells into vascular smooth muscle cells. METHODS:Bone marrow mesenchymal stem cells were isolated and extracted from SD rats.The bone marrow mesenchymal stem cells were inoculated separately on polycaprolactone(PCL),polycaprolactone-hyaluronic acid(PCL-HA),polycaprolactone-silk-filament proteins(PCL-SF),and polycaprolactone-gelatin(PCL-GEL)electrospinning membrane materials.After 1,3,and 7 days of culture,the cell arrangement on the material was observed under scanning electron microscope.The proliferation and adhesion of the material were observed by phalloidin staining.The mRNA expressions of CD90,Meflin,and transforming growth factor β were detected by qRT-PCR.After 7 days of induced differentiation into vascular smooth muscle cells,the mRNA expression ofɑ-smooth muscle actin on the material was detected by qRT-PCR. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells were arranged along the fibers of the four kinds of electrospinning membranes under scanning electron microscopy.(2)Phalloidin staining showed the regular distribution of bone marrow mesenchymal stem cells on the four kinds of electrospinning membranes and parallel distribution along the fiber direction.Moreover,PCL-HA,PCL-SF,and PCL-GEL electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells than PCL electrospinning membranes.Compared with PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells.(3)qRT-PCR showed that the four kinds of electrospun membrane materials could maintain the mRNA expression of CD90 and Meflin in bone marrow mesenchymal stem cells,but there was no significant difference between groups(P>0.05).The mRNA expression of transforming growth factor β in PCL-HA,PCL-SF,and PCL-GEL groups was higher than that in PCL group on days 1 and 7(P<0.05),and the mRNA expression of transforming growth factor β in PCL-SF group was higher than that in the other three groups on days 3 and 7(P<0.05).The mRNA expression of transforming growth factor β in PCL-HA group was higher than that in PCL-GEL group on day 7(P<0.05).(4)qRT-PCR showed that the mRNA expression of ɑ-smooth muscle actin in PCL-SF group was higher than that in the other three groups(P<0.05),and that in PCL-HA group was higher than that in PCL group(P<0.05).(5)The results indicate that compared with PCL,PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes combined with bone marrow mesenchymal stem cells are more suitable for the preparation of small diameter tissue engineered vessels.

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55％)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89％)receiving folic acid supplementation during pregnancy and 496 patients(65.35％)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14％.Compared with those who received folic acid supplementation before pregnancy for＜3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95％CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95％CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95％CI 1.06-1.75))and macrosomia(aRR2.11,95％CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95％CI 1.01-2.34)and 2.43(95％CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P＜0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.