Objective To investigate the relationship of triglyceride-glucose(TyG)index and atherogenic index of plasma(AIP)with positive remodeling of coronary arteries in elderly coro-nary heart disease(CHD)patients with concomitant type 2 diabetes mellitus(T2DM).Methods A total of 120 elderly CHD patients with concomitant T2DM admitted to our department from January 2022 to June 2023 were continuously recruited,and according to the remodeling index,they were divided into positive remodeling group(47 cases)and non-positive remodeling group(73 cases).The clinical data were compared between the two groups.Multivariate logistic analysis was used to identify the risk factors for positive remodeling of coronary artery.Spearman correla-tion analysis was employed to analyze the correlation of TyG and AIP with positive remodeling.ROC curve was plotted to analyze the predictive value of TyG and AIP for the remodeling.Results The positive remodeling group had larger ratio of smoking,higher TG and HbA1c levels,and in-creased TyG index and AIP,but lower HDL-C and blood calcium levels than the non-positive re-modeling group(P＜0.05,P＜0.01).Univariate logistic regression analysis showed that smoking,TG,HDL-C,HbA1c,blood calcium,TyG and AIP were risk factors for positive coronary artery remodeling in elderly patients with CHD and T2DM(P＜0.05,P＜0.01).Multivariate logistic re-gression analysis showed that TyG index(OR=7.253,95％CI:2.458-13.364,P=0.035)and AIP(OR=6.017,95％CI:2.205-12.025,P=0.030)were independent risk factors for positive coronary artery remodeling in elderly patients with CHD and T2DM(P＜0.05).The AUC value of TyG index and AIP in predicting positive coronary artery remodeling in elderly CHD patients with T2DM was 0.783 and 0.766,respectively,and the value of their combination in the prediction was 0.868,which was significantly better than the indicator alone(P＜0.05).Conclusion TyG in-dex and AIP are closely associated with positive coronary artery remodeling in elderly CHD pa-tients with T2DM,and can be used as effective indicators in the prediction of positive remodeling,which is of great significance for early clinical identification of high-risk patients and formulation of individual intervention strategies.

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

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 explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

Objective To investigate the relationship of triglyceride-glucose(TyG)index and atherogenic index of plasma(AIP)with positive remodeling of coronary arteries in elderly coro-nary heart disease(CHD)patients with concomitant type 2 diabetes mellitus(T2DM).Methods A total of 120 elderly CHD patients with concomitant T2DM admitted to our department from January 2022 to June 2023 were continuously recruited,and according to the remodeling index,they were divided into positive remodeling group(47 cases)and non-positive remodeling group(73 cases).The clinical data were compared between the two groups.Multivariate logistic analysis was used to identify the risk factors for positive remodeling of coronary artery.Spearman correla-tion analysis was employed to analyze the correlation of TyG and AIP with positive remodeling.ROC curve was plotted to analyze the predictive value of TyG and AIP for the remodeling.Results The positive remodeling group had larger ratio of smoking,higher TG and HbA1c levels,and in-creased TyG index and AIP,but lower HDL-C and blood calcium levels than the non-positive re-modeling group(P＜0.05,P＜0.01).Univariate logistic regression analysis showed that smoking,TG,HDL-C,HbA1c,blood calcium,TyG and AIP were risk factors for positive coronary artery remodeling in elderly patients with CHD and T2DM(P＜0.05,P＜0.01).Multivariate logistic re-gression analysis showed that TyG index(OR=7.253,95％CI:2.458-13.364,P=0.035)and AIP(OR=6.017,95％CI:2.205-12.025,P=0.030)were independent risk factors for positive coronary artery remodeling in elderly patients with CHD and T2DM(P＜0.05).The AUC value of TyG index and AIP in predicting positive coronary artery remodeling in elderly CHD patients with T2DM was 0.783 and 0.766,respectively,and the value of their combination in the prediction was 0.868,which was significantly better than the indicator alone(P＜0.05).Conclusion TyG in-dex and AIP are closely associated with positive coronary artery remodeling in elderly CHD pa-tients with T2DM,and can be used as effective indicators in the prediction of positive remodeling,which is of great significance for early clinical identification of high-risk patients and formulation of individual intervention strategies.

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

Salvia miltiorrhiza Bunge （Lamiaceae） is a medicinal plant widely used in Traditional Chinese Medicine for treating cardiovascular and cerebrovascular diseases. Chloroplasts are double-membrane-bound, chlorophyll-containing organelles and responsible for photosynthesis in plant cells. The structural information of chloroplast genomes serves as the foundation for precise exogenous gene insertion, site selection, and chloroplast genome modification. In this study, a comprehensive analysis and comparison of 125 chloroplast genomes from S. miltiorrhiza and 76 congeneric species were conducted, focusing on sequence characteristics, codon usage bias, simple sequence repeats （SSRs）, contraction/expansion of chloroplast genome boundaries, and phylogenetic relationships, which could provide a theoretical foundation for advancing chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification within the Salvia genus.

Molecularly defined renal carcinoma is a pathologic subtype of renal cell cancer (RCC) with a definite driver gene, which was first proposed in the 2022 WHO classification of tumors of the urinary system and male reproductive organs. The fumarate hydratase-deficient renal cell carcinoma and SMARCB1-deficient renal medullary carcinoma are highly aggressive and lethal subtypes. Due to the low incidence and lack of research on the mechanism, there is almost no effective treatment for these aggressive RCC subtypes. Cytoreductive nephrectomy or metastasectomy are important methods to improve the survival and quality of life of metastatic RCC patients under effective systemic therapy. However, for the highly aggressive RCC, the clinical value of the above surgical strategies is still unclear. In this review, we will discuss these problems in order to provide reference for the improvement of prognosis for patients with highly aggressive RCC subtypes.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.