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 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 To investigate the expression of ITGBL1 in hepatocellular carcinoma (HCC) and its role in promoting the proliferation, migration, and invasion of HCC cell lines. Methods RT-qPCR and immunohistochemistry were used in investigating ITGBL1 expression in 12 pairs of fresh HCC and adjacent normal liver tissue samples and 160 paraffin HCC specimens. The relationships of ITGBL1 expression level with clinicopathological parameters and prognosis were analyzed. HUH7 cell line with the stable overexpression of ITGBL1 and LM3 cell line with stable downregulated expression of ITGBL1 were constructed. The effects of ITGBL1 on the proliferation, migration, and invasion of HCC cells were examined by CCK8 assay, wound-healing assay, and Transwell invasion assay. Results The expression levels of ITGBL1 gene and protein in tumor tissues were higher than those in surrounding liver tissues. The high expression of ITGBL1 was correlated with serum AFP level, tumor capsular invasion, vascular invasion, tumor differentiation, and clinical stage (P < 0.05). The results of Kaplan-Meier analysis showed that patients with high expression of ITGBL1 had shorter DFS. In vitro, increased ITGBL1 expression promoted HCC cell proliferation, migration, and invasion, whereas ITGBL1 knockdown inhibited these processes. Conclusion ITGBL1 expression is highly expressed in HCC tissues, and ITGBL1 can increase the proliferation, migration, and invasion of HCC cells. However, the mechanism needs further study.

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.

Esophageal squamous cell carcinoma(ESCC)is a major histological subtype of esopha-geal cancer with a poor prognosis.Although several serum metabolomic investigations have been reported,ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined.Here,we enrolled 34 treatment-naive patients with ESCC and collected their pre-and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabo-lomic survey.Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites.Notably,postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome.Furthermore,we performed an examina-tion using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans.Notably,among these metabolites,the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization,and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice.Furthermore,this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest.Together,this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitor-ing therapeutic efficacy and disease relapse,presented evidence for refining parenteral nutrition composition,and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

The mechanisms underlying pregnancy complications caused by advanced maternal age(AMA)remain unclear.We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms.Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing(scRNA-seq).Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications.Trophoblast cells were obtained from the placentas of another six pregnant women(three AMA women and three controls),and in-vitro transwell assays were conducted to observe the cell invasion ability.Thirty additional samples(from 15 AMA women and 15 controls)were analyzed to verify the specific expression of serine protease inhibitor clade E member 1(SERPINE1).Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells.High-quality transcriptomes of 27 607 cells were detected.Three types of trophoblast cells were detected,which were further classified into eight subtypes according to differences in gene expression and Gene Ontology(GO)function.We identified 110 differentially expressed genes(DEGs)in trophoblast cells between the AMA and control groups,and the DEGs were enriched in multiple pathways related to cell invasion.In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced.SERPINE1 was specifically expressed in the trophoblast,and its expression was higher in AMA women(P＜0.05).Transfection of human SERPINEl(hSERPINE1)into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group.Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women.Abnormal expression of SERPINE1 in extravillous trophoblast(EVT)cells appears to play an important role.

To compare the incidence of hypoglycemia between day-before bowel preparation and split-dose bowel preparation in colonoscopy patients. The effects of enterald ietary nutrients on the prevention of hypoglycemia and the preparation quality of the intestine during colonoscopy were compared. The patients who underwent colonoscopy were divided into the day-before bowel preparation group, the split-dose bowel preparation group, and the split-dose bowel preparation + enteral nutrient diet group. All patients had their finger blood sugar tested before colonoscopy. The peripheral blood glucose level was measured before operation. After the endoscopic examination, the intestinal cleanliness of the patients was evaluated through the Boston intestinal preparation scale by endoscopists. The incidence of day-before bowel preparation group and split-dose bowel preparation group and enteral nutrient intervention group were 14.38%(23/160), 17.50% (28/160)and 6.45% (4/62), respectively. The proportions of high quality intestinal cleaning were 31.25% (50/160), 35.00% (56/160) and 82.26% (51/62) in the three groups respectively. The incidence of hypoglycemia was higher in split-dose bowel preparation group than that in day-before bowel preparation group. Enteral nutrient intervention can effectively reduce the incidence of hypoglycemia and improve the quality of intestinal preparation, which is a recommended intestinal preparation method.