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 analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.

Objective To construct a prognostic model of future asthma exacerbation risk in adults by com-bining novel biomarkers of serum chitinase-3-like protein 1(YKL-40),dipeptidyl peptidase-4(DPP4)and conventional predictors.Methods Patients with asthma in the non-acute exacerbation phase were recruited from the People's Hospital of Yubei District of Chongqing,from March 2022 to May 2023.Baseline clinical da-ta collected included medical history,forced expiratory volume in the first second(FEV1)/forced vital capacity(FVC),percentage of predicted forced expiratory volume in the first second(FEV1％pred),blood eosinophil count(EOS),blood neutrophil count(NEU),fractional exhaled nitric oxide(FeNO),serum YKL-40,and ser-um DPP4,etc.The patients were followed for one year to gather data on asthma acute exacerbations and their timings as defined in this study.A COX proportional hazards regression model was used to construct a prog-nostic model for future asthma exacerbations,with internal validation and results presentation.Results A to-tal of 224 patients with asthma completed the study.During the one-year follow-up period,102 patients experi-enced acute exacerbations as defined in this study.Based on univariate COX regression,stepwise regression for variable selection,clinical significance,and model simplicity,asthma control test(ACT)score group,number of asthma exacerbations in the past year group,log10(YKL-40),log10(FeNO),log10(EOS),and FEV1％pred were the following predictors were included in the final model.The overall C-statistic of the model was 0.795(95％CI:0.754-0.836),the area under the curve at the 52-week follow-up was 0.879(95％CI:0.834-0.924),and the Brier score at the 52-week follow-up was 0.142(95％CI:0.117-0.168).The calibration curve was close to a slope of 1,and bootstrap validation suggested good stability of the prediction model.The model was presented using a Nomogram and a dynamic scoring table in a web APP,which can be used to predict the risk of asthma exacerbations within 52 weeks for individual patients.Conclusion The prediction model based on serum YKL-40,EOS,FeNO,the number of asthma exacerbation in the past year group,FEV1％pred and ACT scores group can accurately predict the probability of acute attacks in 52 weeks of asthma patients.

The research on the mechanism of Chinese materia medica in the treatment of viral pneumonia (VP) is mainly based on the monomer components of Chinese materia medica and TCM compounds. Among them, the monomer components are mainly polyphenols, flavonoids and anthraquinones, which have anti-inflammatory, antiviral, immunomodulatory and antioxidant pharmacological effects. The efficacy of TCM compounds is mainly based on clearing heat, and it has the functions of removing phlegm, removing blood stasis, removing dampness, moistening lung and so on. The intervention of Chinese materia medica in VP mainly involves NF-κB, MAPK, JAK/STAT, PI3K/Akt and other signaling pathways. The mechanism includes regulating oxidative stress, apoptosis, regulating immune function, inhibiting inflammatory response, etc., which can reduce the pathological damage of inflammatory cell infiltration and edema in lung tissue, and achieve the protective effect on lung tissue. The current research models exhibit unclear patterns of syndrome differentiation, and the mechanisms of Chinese materia medica involving multiple targets and pathways are poorly understood. Future research should integrate disease-syndrome combination models to further explore the mechanisms by which TCM regulates multiple targets and pathways, thereby providing insights and methodologies for the treatment of viral pneumonia with Chinese materia medica.

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.

Viral pneumonia is an infectious disease caused by virus invading the lung parenchyma and interstitial tissue and causing lung inflammation， with the incidence rising year by year. Traditional Chinese medicine （TCM） can treat viral pneumonia in a multi-component， multi-target， and holistic manner by targeting the core pathogenesis of pneumonia caused by different respiratory viruses， demonstrating minimal side effects and significant advantages. According to the theory of healthy Qi and pathogenic Qi in TCM， the struggle between healthy Qi and pathogenic Qi and the imbalance between immunity and inflammation run through the entire process of viral pneumonia， and the immunity-inflammation status at different stages of the disease reflects different relationships between healthy Qi and pathogenic Qi. Immune dysfunction leads to the deficiency of healthy Qi， causing viral infections. The struggle between healthy Qi and pathogenic Qi causes immunity-inflammation imbalance， leading to the onset of viral pneumonia. Inflammatory damage causes persistent accumulation of phlegm and stasis， leading to the progression of viral pneumonia. The cytokine storm causes immunodepletion， leading to the excess of pathogenic Qi and diminution of healthy Qi and the deterioration of viral pneumonia. After the recovery from viral pneumonia， there is a long-term imbalance between immunity and micro-inflammation， which results in healthy Qi deficiency and pathogenic Qi lingering. Healthy Qi deficiency and pathogenic Qi excess act as common core causes of pneumonia caused by different respiratory viruses. Clinical treatment should emphasize both replenishing healthy Qi and eliminating pathogenic Qi， helping to restore the balance between healthy Qi and pathogenic Qi as well as between immunity and inflammation， thus promoting the recovery of patients from viral pneumonia. According to the TCM theory of healthy Qi and pathogenic Qi， this article summarizes the immunity-inflammation mechanisms at different stages of viral pneumonia， and explores the application of the method of replenishing healthy Qi and eliminating pathogenic Qi in viral pneumonia. The aim is to probe into the scientific connotation of the TCM theory of healthy Qi and pathogenic Qi in viral pneumonia and provide ideas for the clinical application of the method of replenishing healthy Qi and eliminating pathogenic Qi to assist in the treatment of viral pneumonia.

The principle of treating different diseases with the same therapy is the essence of syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It means that when the same pathogenic changes or the same symptoms appear in the development of different diseases， the same principles or methods can be used for treatment. Due to the complexity and high variability of viral pathogenicity， the precise and effective treatment of different types of viral pneumonia （VP） has always been a research focus and difficulty in modern medicine. VP belongs to the category of external-contraction febrile disease， warm disease， and epidemic in TCM. Haoqin Qingdantang （HQQDD） is a representative formula for clearing heat and dispelling dampness in warm diseases， and its intervention in VP caused by various viral infections has significant effects. This study， guided by the theory of treating different diseases with the same therapy， links the related studies on using HQQDD to treat different types of VP and finds that influenza virus pneumonia （IVP）， severe acute respiratory syndrome （SARS）， and COVID-19 all have a common pathogenic mechanism of dampness-heat at different stages of respective diseases. When these diseases are dominated by damp-heat factors， the use of HQQDD yields remarkable therapeutic effects. Modern pharmacological studies have confirmed that HQQDD can inhibit virus replication， reduce fever reactions， inhibit the expression of inflammatory mediators， and regulate immune balance. Moreover， the sovereign medicine in this formula has excellent antiviral activity， and the formula reflects rich scientific connotations of treating VP. According to the theory of treating different diseases with the same therapy and based on the effective treatment practice and modern pharmacological research of HQQDD for different types of VP， this paper mines the underlying TCM theory of treatment with the same therapy， explores the syndrome differentiation and treatment strategy and effect mechanism of this formula for different types of VP， and analyzes the treatment mechanism and characteristics， with the aim of providing evidence and reference for the clinical application and modern research of HQQDD.