ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Objective: To understand the changing trends and related factors of knowledge, attitude and practice (KAP) regarding the three major infectious diseases (acquired immunodeficiency syndrome, tuberculosis, hepatitis B) among freshmen in Jiangsu from 2019 to 2022, so as to provide a reference basis for the health education of infectious diseases in schools. Methods: From 2019 to 2022, a total of 33 944 freshmen from 20 universities in Jiangsu Province were randomly selected for four consecutive years to investigate their KAP levels online through self designed questionnaires on three major infectious diseases. The multiple linear regression model was used to analyze the changing trends of students KAP levels of the three major infectious diseases, and to explore the influencing factors of KAP. Results: From 2019 to 2022, the knowledge scores(18.0±3.1,18.4±3.2,18.7±3.2,18.8±3.2), related to the three major infectious diseases showed an upward trend ( F=436.50, P <0.01), and the positive attitude reporting rates were 81.77%, 81.46%, 82.68% and 81.74%, respectively. The reporting rates of positive practice were 80.11%, 79.25%, 79.08 % and 79.04%, respectively. Multiple linear regression showed that school type, parental education level, mother s occupation, average income per person in family and living arrangements during high school all had an impact on the knowledge ( β = -1.510 -0.559), attitudes ( β =-0.043-0.065) and practice ( β =-0.028-0.027) of the three major infectious diseases ( P < 0.05 ). The family residence areas only affected the reporting rate of positive attitude scores ( β =0.002-0.065), and whether only children or not affected the reporting rate of positive practice scores ( β =0.009)( P <0.05). The knowledge score showed an upward trend ( β= 0.297, P <0.01), the positive attitude reporting rate showed no statistically significant change ( β=0.001, P =0.22), and the positive practice reporting rate showed a downward trend ( β=-0.005, P <0.01). Conclusions Freshman in Jiangsu Province from 2019 to 2022 have shown a separation in KAP scores regarding the three major infectious diseases. Targeted measures should be taken to improve their health practice level.

Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp^-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Oral Submucous Fibrosis/pathology* ; Cartilage Oligomeric Matrix Protein/genetics* ; Animals ; Mice ; Humans ; Fibroblasts/metabolism* ; Collagen Type I/metabolism* ; Arecoline/pharmacology* ; Mouth Mucosa/metabolism* ; Cells, Cultured ; Fluorescent Antibody Technique

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42％)achieved clinical response,and 30 recipients(69.77％)achieved microbial response.34 recipients(79.07％)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P＜0.05),while the serum albumin(ALB)level was higher(P＜0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P＜0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P＜0.05),while ALB level was higher during treatment period(P＜0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95％CI:1.07-4.63),while lower ALB levels(OR=0.72,95％CI:0.54-0.98)and higher CCI(OR=5.27,95％CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.

Objective:To establish fingerprints and method for determining the content of two components of Qigong Pills.Methods:High performance liquid chromatography (HPLC) was used to establish the fingerprints of 10 batches of Qigong Pills and common peaks were identified. TCM Chromatographic Fingerprint Similarity Evaluation System (2012 Edition) was used for similarity analysis; the common peaks area was used as indicators, and SIMCA 14.1 was used for cluster analysis and principal component analysis for quality evaluation; a content analysis method was established using hesperidin and Atractylodes macrocephala as indicator components.Results:21 common peaks in the 10 batches of Qigong Pills were identified with the similarity greater than 0.952 (except for the sample S6); the clustering analysis results showed that at a measurement distance of 8, S6 was clustered into one category alone, S1 and S2 were clustered into one category, and the remaining samples were clustered into one major category. The content of hesperidin and Atractylodes macrocephala in 10 batches of Qigong Pills was 3.61-8.92 mg/g and 0.07-0.72 mg/g, respectively.Conclusion:The established HPLC fingerprints and content determination method in this study are stable, reliable, and reproducible, which can provide reference for quality control and evaluation of Qigong Pills.

Objective:To investigate the incidence and high-risk pathogenic factors of cardiovascular disease（CVD）in patients with rheumatic and autoimmune diseases，and to construct and validate a predictive model for the risk of CVD occurrence in these patients.Methods:A retrospective analysis was conducted on 239 patients with rheumatic and autoimmune diseases who underwent treatment and echocardiography at the Affiliated Hospital of Inner Mongolia Medical University between June 2020 and June 2023. General patient data，laboratory test results，and echocardiographic findings were collected. Follow-up was performed via electronic medical records or telephone surveys until December 2024 to determine the incidence of CVD，starting from the date of the first echocardiographic examination. Predictive factors were screened using univariate analysis and Lasso regression，and a Logistic regression model was constructed. Internal validation was performed using the Bootstrap method. The model's accuracy and clinical utility were assessed using the Hosmer-Lemeshow test，calibration curve，and decision curve analysis.Results:Among the 239 patients，111 developed CVD. Logistic regression analysis identified age，diastolic blood pressure，use of immunosuppressants，lymphocyte count（LYM），α-hydroxybutyrate dehydrogenase（α-HBDH）level，serum cystatin C（CysC），and right ventricular fractional area change（RVFAC）as independent predictive factors for CVD in these patients（all P<0.05）. The area under the ROC curve（AUC）for the prediction model was 0.895（95% CI = 0.856 - 0.935），and after Bootstrap validation，it was 0.894（95% CI = 0.861-0.925）. The Hosmer-Lemeshow test，calibration curve，and decision curve analysis all indicated that the model had good accuracy and clinical utility. Conclusions:Age，diastolic blood pressure，use of immunosuppressants，LYM，α-HBDH，CysC，and RVFAC may serve as independent risk factors for CVD in patients with rheumatic and autoimmune diseases. The prediction model based on echocardiography combined with laboratory indicators can，to some extent，predict the risk of CVD occurrence in these patients.