Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct^+/+ mice, placentae and embryos (Qpct^-/+ and Qpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct^+/+ and Qpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct^+/+ and 3285 Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct^-/+ and Qpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals ; Female ; Pregnancy ; Mice ; Placentation/genetics* ; Single-Cell Analysis ; Gene Expression Profiling ; Mice, Knockout ; Transcriptome ; Placenta/blood supply* ; Neovascularization, Pathologic/genetics* ; Genomic Imprinting ; Single-Cell Gene Expression Analysis ; Angiogenesis

Objective To investigate the relationship between traditional Chinese medicine(TCM)constitution and body composition such as visceral fat in overweight and obese individuals.Methods A total of 320 overweight/obese patients who visited the Preventive Treatment Center of Foshan Hospital of Traditional Chinese Medicine between September 15,2023,and September 14,2024,were selected as study subjects.Among them,135 were classified into the overweight group and 185 into the obese group.Data were collected using the TCM Constitution Questionnaire and a body composition analyzer(InBody570).The differences in TCM constitution distribution between the overweight and obese groups,as well as between genders,were compared.The correlation between TCM constitution types and body composition parameters was analyzed.Logistic regression analysis was employed to identify risk factors for biased constitutions in the overweight/obese population.Results Among the 320 overweight/obese patients,phlegm-damp constitution(56.25％)and damp-heat constitution(40.31％)were the most predominant biased constitutions.The proportions of blood stasis constitution,qi depression constitution,and inherited special constitution in females were significantly higher than those in males(P＜0.05 or P＜0.01),with the risk of qi depression constitution in females being 6.028 times higher than that in males(P＜0.01).Yang deficiency constitution was positively correlated with protein content but negatively correlated with skeletal muscle mass and body fat mass(P＜0.05).The proportion of blood stasis constitution in the overweight group was higher than that in the obese group(P＜0.01).In overweight/obese individuals with blood stasis constitution,the risk of excessive visceral fat was 2.658 times as high as those without excessive visceral fat.Blood stasis constitution was positively correlated with body fat mass,bone mineral content,intracellular water,and skeletal muscle mass index(SMI),but was negatively correlated with body mass index(BMI)and body cell mass(P＜0.05 or P＜0.01).Coclusion For overweight and obese populations,special attention should be paid to the management of visceral fat in individuals with blood stasis constitution and to emotional intervention in females.A staged and precise prevention and treatment strategy should be developed by integrating TCM constitution and body composition indicators.

Aim Based on coronary CT-fractional flow reserve(CT-FFR)combined with machine learning methods,a nomogram prediction model for coronary in-stent restenosis(ISR)was developed to assess the risk of ISR.Methods Retrospective analysis was performed on patients who underwent re-examination after PCI at our hospital from January 2022 to January 2025.According to the exclusion criteria,a total of 210 patients were enrolled,including 100 cases of ISR and 110 cases of non-ISR.The dataset was randomly divided into training and test sets at a 7∶3 ratio.Af-ter univariate analysis to screen potential predictors,LASSO regression was applied to identify feature variables with non-ze-ro coefficients.Subsequently,three machine learning(ML)algorithms including random forest(RF),support vector machine(SVM),and extreme gradient boosting(XGB)were used to rank the importance of the significant factors.The intersection of the top 10 variables from each algorithm was used as input for bidirectional stepwise multivariate Logistic re-gression.An ISR risk score was then constructed and visualized using a nomogram.Results A total of 14 predictive factors were identified through LASSO regression,including diastolic blood pressure,C-reactive protein,triglycerides(TG),N-terminal pro-brain natriuretic peptide(NT-proBNP),low density lipoprotein cholesterol(LDLC),minimum stent diameter＜3 mm,systolic blood pressure,△CT-FFR,CT-FFR,interleukin-6(IL-6),body mass index,glycosylated hemoglobin(HbA1c),history of hypertension,and high density lipoprotein cholesterol(HDLC).Following stepwise screening using three ML algorithms and Logistic regression,six independent risk factors for ISR were identified:elevated△CT-FFR,IL-6,NT-proBNP,TG and CT-FFR values,and minimum stent diameter＜3 mm.The area under the curve for the training set and test set were 0.995(95％CI:0.989～1.000)and 0.965(95％CI:0.927～1.000),respectively.Decision curve analysis demonstrated high net benefit across threshold probabilities of 0～1.00 in the training set and 0～0.92 in the test set.The nomogram integrating these six predictors exhibited high accuracy and clinical utility.Con-clusion The ISR nomogram prediction model based on LASSO-ML combined with CT-FFR technology has high accuracy and clinical utility for ISR.

Aim Based on coronary CT-fractional flow reserve(CT-FFR)combined with machine learning methods,a nomogram prediction model for coronary in-stent restenosis(ISR)was developed to assess the risk of ISR.Methods Retrospective analysis was performed on patients who underwent re-examination after PCI at our hospital from January 2022 to January 2025.According to the exclusion criteria,a total of 210 patients were enrolled,including 100 cases of ISR and 110 cases of non-ISR.The dataset was randomly divided into training and test sets at a 7∶3 ratio.Af-ter univariate analysis to screen potential predictors,LASSO regression was applied to identify feature variables with non-ze-ro coefficients.Subsequently,three machine learning(ML)algorithms including random forest(RF),support vector machine(SVM),and extreme gradient boosting(XGB)were used to rank the importance of the significant factors.The intersection of the top 10 variables from each algorithm was used as input for bidirectional stepwise multivariate Logistic re-gression.An ISR risk score was then constructed and visualized using a nomogram.Results A total of 14 predictive factors were identified through LASSO regression,including diastolic blood pressure,C-reactive protein,triglycerides(TG),N-terminal pro-brain natriuretic peptide(NT-proBNP),low density lipoprotein cholesterol(LDLC),minimum stent diameter＜3 mm,systolic blood pressure,△CT-FFR,CT-FFR,interleukin-6(IL-6),body mass index,glycosylated hemoglobin(HbA1c),history of hypertension,and high density lipoprotein cholesterol(HDLC).Following stepwise screening using three ML algorithms and Logistic regression,six independent risk factors for ISR were identified:elevated△CT-FFR,IL-6,NT-proBNP,TG and CT-FFR values,and minimum stent diameter＜3 mm.The area under the curve for the training set and test set were 0.995(95％CI:0.989～1.000)and 0.965(95％CI:0.927～1.000),respectively.Decision curve analysis demonstrated high net benefit across threshold probabilities of 0～1.00 in the training set and 0～0.92 in the test set.The nomogram integrating these six predictors exhibited high accuracy and clinical utility.Con-clusion The ISR nomogram prediction model based on LASSO-ML combined with CT-FFR technology has high accuracy and clinical utility for ISR.

Objective:To classify the etiology of secondary hemophagocytic syndrome (sHLH) and explore its clinical, laboratory and therapeutic characteristics in order to deepen the understanding of the disease.Method:A retrospective observational study was conducted on sHLH patients who were treated at Peking University People's Hospital from January 2016 to December 2021. Patients under the age of 18 and those with missing clinical data were excluded. The distribution of departments visited and etiologies of sHLH were analyzed. Baseline data, clinical characteristics, complications, laboratory data, treatment, and in-hospital outcomes of sHLH were collected. The sHLH patients were then divided into 3 groups including malignancy group, macrophage activation syndrome (MAS) group and other etiologies (mainly infection) group. Intergroup comparisons were performed using chi-square tests, analysis of variance, Mann-Whitney tests, and other statistical methods.Results:A total 169 patients were enrolled, among these patients, 27.8% were malignancy-related HLH, 47.9% were MAS, and 24.3% were other etiologies related HLH. Statistical analysis revealed that the clinical characteristics of other etiological group was highly consistent with the malignancy group, including more and severer peripheral blood cell reduction, higher sCD25 levels, more Epstein-Barr virus infection, and the prognosis was similar, both were with more than 50% in-hospital mortality. And the incidence of hemophagocytosis was highest in other etiological groups (65.9%). In contrast, MAS group was with an obviously lower mortality of 17.3% ( P<0.05). Meanwhile, treatments including methylprednisolone pulse, cyclosporine A and interleukin-2 were used frequently in MAS group. Conclusion:Malignancy related HLH and other etiologies related HLH exhibit more similar clinical characteristics and prognosis, while the MAS group, has a milder overall condition and better prognosis.

Objective To analyze the causal relationship of gluteal tendinitis and primary coxarthrosis with the occurrence of iliotibial band syndrome using Mendelian randomization.Methods The GWAS data of gluteal tendinitis,primary coxarthrosis and iliotibial band syndrome were screened for high correlation single-nucleotide polymorphisms(SNPs).Mendelian randomization analysis was performed using random-effects inverse variance weighting(IVW),MR-Egger regression,and weighted median method to determine whether gluteal tendinitis and primary coxarthrosis were causally related with iliotibial band syndrome.Heterogeneity test,multiple validity test and sensitivity analysis,and clinical data analysis were used to verify the reliability of the results.Results Both gluteal tendinitis[IVW:OR(95%CI)=1.32(1.03-1.68),P=0.026]and primary coxarthrosis[IVW:OR(95%CI)=1.40(1.06-1.84),P=0.017]was positively correlated with iliotibial band syndrome.Conclusion Gluteal tendinitis and primary coxarthrosis may increase the risk of iliotibial band syndrome.

ObjectiveTo explore the suitability of four qualitative research methods in the development of TCM scale. MethodsTaking the development of "Seven Emotions Scale" as an example， we conducted semi-structured interviews with 31 patients of emotional disorders and 10 healthy people by objective sampling， and collected psychological feelings and emotional cognition data related to seven emotions according to the interview outline. Two qualitative methods， descriptive qualitative research and descriptive phenomenology， were used to analyze the data and construct the item library of the scale. The conceptual framework of the scale was constructed by using commonly used grounded theory and frame analysis. ResultsDuring data analysis， it is found that the themes extracted from descriptive phenomenology were not easily understood by the interviewees， and it is difficult for the researchers to truly achieve the "suspension" required by phenomenology. Considering the feasibility and convenience of the researchers' actual operation， as well as whether the initial purpose of the scale research can be intuitively included in the interviewees' views and feelings， descriptive phenomenology is not suitable for the formation of scale items. Using descriptive qualitative research method to analyze the interview data of healthy people and patients with emotional disorders， 306 and 476 scale items were obtained respectively. Through grounded theory， five selective codes were obtained： physical symptoms， external manifestations， psychological feelings， behaviors and emotional control. Using frame analysis， four themes including physical symptoms， psychological feelings， behavior and emotional cognition were constructed. Both methods can be used to construct the conceptual frame of scale， but the framework analysis is more convenient and can better ensure the transparency of the research. ConclusionDescriptive qualitative research methods can be used to form the item library of TCM scales. Framework analysis is more suitable for the construction of the conceptual framework of the scale than grounded theory， while descriptive phenomenology is not suitable for the development of TCM scales.

Objective To analyze the causal relationship of gluteal tendinitis and primary coxarthrosis with the occurrence of iliotibial band syndrome using Mendelian randomization.Methods The GWAS data of gluteal tendinitis,primary coxarthrosis and iliotibial band syndrome were screened for high correlation single-nucleotide polymorphisms(SNPs).Mendelian randomization analysis was performed using random-effects inverse variance weighting(IVW),MR-Egger regression,and weighted median method to determine whether gluteal tendinitis and primary coxarthrosis were causally related with iliotibial band syndrome.Heterogeneity test,multiple validity test and sensitivity analysis,and clinical data analysis were used to verify the reliability of the results.Results Both gluteal tendinitis[IVW:OR(95%CI)=1.32(1.03-1.68),P=0.026]and primary coxarthrosis[IVW:OR(95%CI)=1.40(1.06-1.84),P=0.017]was positively correlated with iliotibial band syndrome.Conclusion Gluteal tendinitis and primary coxarthrosis may increase the risk of iliotibial band syndrome.

【Objective】   To explore the prescriptions related to the treatment of spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary (Tai Ping Hui Min He Ji Ju Fang,《太平惠民和剂局方》, TPHMHJJF), and investigate the medication and prescription rules. 【Methods】   The prescriptions of TPHMHJJF for treating spleen and stomach diseases were screened, and the data set was established by entering the prescriptions and standardized drug names using WPS Excel 2019. Herb frequency statistics, efficacy categorization, property, flavor, meridian tropism, association rules, cluster analysis, factor analysis, and complex network analysis were performed using Python 3.6.8 programming language and Gephi 0.9.2 visualization software. 【Results】   A total of 239 prescriptions were included after the screening, and the dosage forms were mainly pills and powders. The study involved 200 herbal medicines, among which 40 herbs had a frequency of ≥ 12. The herb with the highest frequency was Ganjiang (Zingiber Rhizoma). The herb properties were mainly warm in nature, with the most pungent herbs. Most herbs were attributed to the spleen and stomach meridians, and tonifying medicine were the main species. The association rule analysis identified 26 second-order association rules and 16 third-order association rules, with "Renshen (Ginseng Radix et Rhizoma) → Fuling (Poria)" as the leading rule in the former and "Fuling (Poria) + Baizhu (Atractylodis Macrocephalae Rhizome) → Renshen (Ginseng Radix et Rhizoma)" as the leading rule in the latter. Also, cluster analysis divided the top 30 herbs into six herb combinations that can warm the middle, move Qi, and dry dampness effectively. Factor analysis extracted 13 common factors, with Renshen (Ginseng Radix et Rhizoma), Fuling (Poria), and Baizhu (Atractylodis Macrocephalae Rhizome) as the highest contributing factors. Lastly, complex network analysis yielded the core prescription of 14 herbs, with Ganjiang (Zingiber Rhizoma), Renshen (Ginseng Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizome), and Chenpi (Citri Reticulatae Pericarpium) among the herbs with a higher weighting degree. 【Conclusion】  TPHMHJJF is mainly based on the use of warming herbs to treat spleen and stomach diseases, and its medication rule can be summarized into three aspects: (i) primarily using warming and tonifying to warm the middle and dissipate cold, (ii) using the method of moving Qi with aromatic nature to delight the spleen and appetize the stomach, and (iii) emphasizing the regulation of Qi and blood to calm the five zang-organs.