Disease computable phenotype is a data model designed to identify specific clinical conditions or characteristics, which automatically extracts information from clinical databases such as electronic health records through algorithms. Phenotypic data for rare diseases often reside in unstructured text. Due to the scarcity of rare disease cases, atypical symptoms, and insufficient physician experience, misdiagnosis and underdiagnosis rates remain high. In this context, the application of computable phenotype technology holds promise for improving the accuracy and efficiency of rare disease diagnosis. This article reviews the current research status, challenges, and opportunities of computable phenotype technology in biomedicine, particularly in the field of rare diseases, and proposes a development and validation framework for rare disease computable phenotypes, aiming to provide research and development insights for computable phenotypes to empower the diagnosis and treatment of rare diseases.

Diabetic cataract is a prevalent and severe complication of diabetes mellitus. Its pathogenesis is complex and driven by multiple metabolic disorders. Conventional research methods are insufficient to fully clarify its complex pathophysiological processes. As a high-throughput and unbiased systems biology approach, metabolomics allows comprehensive profiling of small-molecule metabolites in biological systems, serving as a robust tool for exploring the metabolic signatures underlying this disease. This review systematically summarizes recent progress in the application of metabolomics to diabetic cataract research, with a focus on technological innovations in sample pretreatment, data acquisition, and bioinformatics analysis. This article elaborates on how these advances contribute to the identification of disease-specific biomarkers, the clarification of intrinsic molecular mechanisms, and the discovery of potential therapeutic targets, ultimately advancing the translational application of metabolomics in the early clinical diagnosis, prognostic assessment, and development of innovative therapeutic strategies for diabetic cataract.

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 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 investigate the safety and feasibility of one-stage flexible ureteroscopic lithotripsy without ureteral access sheath or ureteral stent in the treatment of upper ureteral calculi and renal calculi with a long diameter of≤10 mm.Methods:A total of 70 patients with upper ureteral calculi or renal calculi with a long diameter of≤10 mm who were admitted to Guang'an Hospital,West China Hospital of Sichuan University,from January 2023 to June 2024 were enrolled and randomly divided into experimental group(without ureteral access sheath or ureteral stent)and control group(with ureteral access sheath and ureteral stent),with 35 patients in each group.The patients in the experimental group did not use a ureteral access sheath or a ureteral stent,while those in the control group used the ureteral access sheath and the ureteral stent.The two groups were compared in terms of preoperative data,intraoperative complications,stone clearance rate,length of hospital stay,hospital costs,and postoperative complications.Results:There were no sig-nificant differences between the two groups in preoperative data such as age,body mass index,sex,previous history of stone surgery,af-fected side,maximum stone diameter,C-reactive protein,aggregation system separation,preoperative CT value of stones,and stone lo-cation.The experimental group had a significantly shorter time of operation than the control group[(44.94±52.60)minutes vs.(52.60±14.22)minutes,t=2.240,P=0.030].There were no significant differences between the two groups in intraoperative data such as ureteral injury,intraoperative leukocyte changes,and intraopera-tive blood loss.The experimental group had significantly lower hos-pital costs than the control group[(8041.89±1287.57)yuan vs.(13 011.63±1 780.21)yuan,t=13.450,P=0.000].There were no significant differences between the experimental group and the con-trol group in the postoperative data such as the length of hospital stay,the recurrence of calculi on CT at 1 and 3 months after sur-gery,stone clearance rate,postoperative urinary tract irritation,post-operative ureteral injury,postoperative hematuria,and postoperative hydronephrosis(P>0.05).Conclusion:One-stage flexible uretero-scopic lithotripsy without ureteral access sheath or ureteral stent is safe and feasible in the treatment of upper ureteral calculi and renal calculi with a long diameter of≤10 mm and can effectively reduce hospital costs and time of operation.

Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

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.

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

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.