Objective To explore the mechanism by which hyperandrogenic states induce preeclampsia in advanced maternal age through the LAMA3-PI3K/Akt pathway and assess its effects on the invasion and migration abilities of human trophoblast cells.Methods Human trophoblast cells were stimulated with dihydrotestosterone(DHT),followed by RNA sequencing(RNA-Seq)to identify differen-tially expressed genes,with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis revealing LAM A3 as a key molecule.The mRNA and protein expression levels of LAMA3 were detected using real-time quantitative PCR(RT-qPCR)and Western blot.LAMA3-overexpressing human trophoblast cells were obtained by plasmid transfection.The invasion ability was assessed using the Matrigel-based Transwell assay,and the migration ability was evaluated by the scratch assay.Results DHT stimulation sig-nificantly inhibited the invasion and migration abilities of trophoblast cells.RNA-Seq analysis revealed that LAM A3 might be a key mole-cule involved,and further Western blot and RT-qPCR analyses showed that the protein and mRNA expression of LAM A3 in the placenta of advanced maternal age pregnancies were significantly higher than in normal pregnancies and consistent with findings in the placenta of preeclampsia patients.Overexpression of LAM A3 significantly suppressed trophoblast cell invasion and migration abilities,while also up-regulating the phosphorylation levels of PI3K and Akt.Treatment with a PI3K inhibitor restored both cell function and phosphorylation lev-els to normal.Conclusion Elevated androgen levels in trophoblast cells from advanced maternal age induce specific changes in LAMA3 expression,and LAMA3 regulates trophoblast migration and invasion through the PI3K/Akt signaling pathway.

ObjectiveTo analyze the influencing factors of pulmonary dysfunction among community-based population at high-risk for chronic obstructive pulmonary disease (COPD), and to establish a risk assessment model to provide a reference basis for accelerating the beforehand prevention and control of COPD and promoting the respiratory health of community-based residents. MethodsIndividuals aged >35 years old, with at least one risk factor except age illustrated in the Guidelines for Primary Diagnosis and Treatment of Chronic Obstructive Lung Disease (2018), and participated in the early screening for COPD from July 2022 to December 2023 were selected as the research subjects, and their lung function was assessed by the forceful expiratory volume in the first second after inhalation of bronchodilator (FEV₁)/ forced vital capacity (FVC) <70% and/or the ratio of FEV₁ to predicted value (FEV₁%Pred) <80% as the diagnostic criteria. In addition, risk factors related to pulmonary dysfunction were analyzed for the establishment of risk assessment model. ResultsA total of 823 individuals aged between 35‒76 years were included, among which 298 (36.21%) were diagnosed with pulmonary dysfunction, 167 (20.29%) with COPD, and 131 (15.92%) with preserved ratio but impaired spirometry. Logistic regression analysis revealed that male gender, increasing age, more frequent smoking, insufficient physical activity, recurrent wheezing, the presence of post-exercise wheezing or coughing, insensitive to airborne allergens, and history of chronic bronchitis or bronchial asthma were correlated with pulmonary dysfunction. The incidence rate of pulmonary dysfunction was 1.99 times higher in males than that in females, 1.81 times more common in those aged between 70‒76 years than those aged <60 years, 2.42 times more common in those who smoked 50‒200 pack-years than in those who smoked 0‒14 pack-years, 1.78 times higher in those who underwent physical activity <600 MET‑min·week^-1 than in those who underwent physical activity ≥600 MET‑min·week^-1, 2.61 times higher in those suffered recurrent wheezing than in those did not, 1.53 times higher in those with symptoms of post-exercise wheezing or coughing than in those without, 1.61 times higher in those insensitive to airborne allergens than those sensitive, 2.02 times higher in patients with chronic bronchitis than in those without, and 2.41 times higher in patients with bronchial asthma than in those without. The risk assessment model for pulmonary dysfunction constructed on this basis had a total score of 28 points, and the area under the subject operating characteristic (ROC) curve was 0.72, reaching the cut-off point of ROC curve while taking scores ≥10 points as the cut-off value for pulmonary dysfunction. ConclusionIn community-based high-risk COPD population, the incidence rate of pulmonary dysfunction is higher in males than that in females, in addition, which increases with the advancement of age. Smoking,insufficient physical activity,recurrent wheezing,post-exercise wheezing or coughing,insensitive to airborne allergens,and history of chronic bronchitis or bronchial asthma are high risk factors for pulmonary dysfunction. The risk assessment model constructed based on these factors has a good predictive effect in screening high-risk population of COPD, but its effectiveness in screening people at general risk needs to be further validated.

ObjectiveTo investigate the mechanism of the modified of Bazhentang combined with Guishentang in improving pregnancy outcomes in mouse models of embryo implantation dysfunction by regulating T helper 1/T helper 2 （Th1/Th2） immune balance. MethodsEighty ICR female mice were randomly divided into four groups （n=20 per group） on gestational day 1 （GD1）： control， model， western medicine， and traditional Chinese medicine （TCM） groups. Except for the control group， all mice received mifepristone solution （0.2 mg/mouse） via oral gavage on GD4 to induce embryo implantation dysfunction. The TCM group received a water decoction of the modified of Bazhentang combined with Guishentang （20.8 g·kg^-1）， with the western medicine group administered dydrogesterone （3.9 mg·kg^-1）， and the control/model groups given equal volumes of saline. All treatments were administered once daily from GD1 until one day before sample collection. Outcomes included implantation site counts （macroscopic observation）， pregnancy rates， body weight， endometrial histopathology （hematoxylin-eosin staining）， uterine expression of T-box expressed in T cells （T-bet）， GATA-binding protein 3 （GATA3）， interferon gamma （IFN-γ）， and interleukin-4 （IL-4） at protein （Western blot） and mRNA （real-time polymerase chain reaction， Real-time PCR） levels， serum IFN-γ and IL-4 levels （enzyme-linked immunosorbent assay， ELISA）， and Th1/Th2 immune balance evaluated by calculating T-bet/GATA3 and IFN-γ/IL-4 ratios. ResultsCompared to the control group， the model group showed no significant change in pregnancy rate but exhibited a marked reduction in average implantation sites and body weight （P<0.01）. Histopathological analysis revealed endometrial abnormalities， including decreased glandular density， stromal compaction， and absence of nucleolar vacuoles. At the molecular level， uterine tissue in the model group demonstrated significantly upregulated expression of T-bet and IFN-γ （P<0.05， P<0.01）， alongside markedly downregulated GATA3 and IL-4 expression （P<0.05， P<0.01）. Serum analysis confirmed markedly elevated IFN-γ （P<0.01） and reduced IL-4 levels （P<0.01）， resulting in significantly increased T-bet/GATA3 and IFN-γ/IL-4 ratios （P<0.01）. Compared to the model group， pregnancy rates in all treatment groups showed no significant change. Implantation sites and body weight increased substantially （P<0.01）， with restored endometrial morphology characterized by enhanced glandular density， stromal edema， and reappearance of nucleolar vacuoles. Significant downregulation of T-bet and IFN-γ （P<0.01） and upregulation of GATA3 and IL-4 （P<0.05， P<0.01） in uterine tissue were observed. Serum IFN-γ levels were significantly reduced （P<0.05， P<0.01）， while IL-4 levels were significantly elevated （P<0.05）. The Th1/Th2 ratios were significantly decreased （P<0.01）. ConclusionThe modified of Bazhentang combined with Guishentang significantly enhances the number of embryo implantation sites in mice with embryo implantation dysfunction， potentially through modulating T-bet/GATA3 expression， restoring Th1/Th2 immune balance， and improving endometrial receptivity.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.

Objective To explore the mechanism by which hyperandrogenic states induce preeclampsia in advanced maternal age through the LAMA3-PI3K/Akt pathway and assess its effects on the invasion and migration abilities of human trophoblast cells.Methods Human trophoblast cells were stimulated with dihydrotestosterone(DHT),followed by RNA sequencing(RNA-Seq)to identify differen-tially expressed genes,with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis revealing LAM A3 as a key molecule.The mRNA and protein expression levels of LAMA3 were detected using real-time quantitative PCR(RT-qPCR)and Western blot.LAMA3-overexpressing human trophoblast cells were obtained by plasmid transfection.The invasion ability was assessed using the Matrigel-based Transwell assay,and the migration ability was evaluated by the scratch assay.Results DHT stimulation sig-nificantly inhibited the invasion and migration abilities of trophoblast cells.RNA-Seq analysis revealed that LAM A3 might be a key mole-cule involved,and further Western blot and RT-qPCR analyses showed that the protein and mRNA expression of LAM A3 in the placenta of advanced maternal age pregnancies were significantly higher than in normal pregnancies and consistent with findings in the placenta of preeclampsia patients.Overexpression of LAM A3 significantly suppressed trophoblast cell invasion and migration abilities,while also up-regulating the phosphorylation levels of PI3K and Akt.Treatment with a PI3K inhibitor restored both cell function and phosphorylation lev-els to normal.Conclusion Elevated androgen levels in trophoblast cells from advanced maternal age induce specific changes in LAMA3 expression,and LAMA3 regulates trophoblast migration and invasion through the PI3K/Akt signaling pathway.

Objective To explore the relationship between androgen level and adverse pregnancy outcome of pregnant women at advanced maternal age.Methods A total of 192 pregnant women who were admitted to Changzhou Maternal and Child Health Care Hospital for delivery from May to October 2022 were selected as the study objects.According to guidelines for diagnosis and treatment of hypertensive disorder complicating pregnancy and maternal age,the study objects were divided into simple pregnant women at advanced maternal age group,pregnant women at advanced maternal age complicated with hypertensive disorder complicating pregnancy,healthy control group and age-appropriate pregnant women complicated with hypertensive disorder complicating pregnancy group.Serum levels of five androgens[total testosterone(TT),sex hormone binding globulin(SHBG),free testosterone index(FTI),dehydroepiandrosterone sulfate(DHEAS)and androstendi-one(A2)]in each group were detected by chemiluminescence method.Results Compared with the healthy control group,TT,A2,FTI were significantly increased and SHBG was significantly decreased in the age-ap-propriate pregnant women complicated with hypertensive disorder complicating pregnancy group,the level of DHEAS was decreased in the simple pregnant women at advanced maternal age group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that TT was negatively correla-ted with age(P＜0.05),positively correlated with systolic blood pressure,diastolic blood pressure and body mass index(P＜0.05),and had no correlation with offspring sex and offspring weight(P＞0.05).Multivari-ate Logistic regression analysis showed that TT and body mass index were independent risk factors for hyper-tensive disorder complicating pregnancy in pregnant women(P＜0.05).Conclusion The level of androgen in pregnant women at advanced maternal age is related to the occurrence of hypertensive disorder complicating pregnancy.

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:Using the classical concept analysis method of Avant & Walker, this paper made an in-depth analysis of the concept of childbirth trauma, obtained its operational definition, and provided a reference for clinical practice.Methods:We systematically searched CNKI, VIP, Wanfang, SinoMed, Web of Science, PubMed, and Embase, and the retrieval period was from the establishment of the database to August 10, 2022. We analyzed and defined childbirth trauma by Avant & Walker's classical concept analysis.Results:A total of 34 articles were included. The defining attributes of childbirth trauma were identified as persistent psychological trauma, lack of social support, loss of control, impaired dignity, and poor interaction with care providers. The antecedents could be discussed from demographic factors and disease history, obstetric nurses and midwives, and delivery environment. Consequences included affected women's physiology, behavior, and psychology.Conclusions:Birth trauma has brought lasting negative consequences to women's lives and families. Medical staff should recognize its severity, identify birth trauma in clinical practice with the help of the concept of birth trauma and operational definition, find it early, and effectively prevent it.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.