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.

ObjectiveTo evaluate the effect of sex on phenotypic stability in mouse models of chemotherapy-induced alopecia (CIA) induced by cyclophosphamide (CYP) or paclitaxel (PTX), and to explore potential mechanisms underlying phenotypic heterogeneity in female mice. MethodsTwenty-eight wild-type specific pathogen-free (SPF) C57BL/6J mice (half male and half female) aged 6-8 weeks were selected for synchronous back hair removal. On the 9th day after hair removal (T0), the mice were randomly divided into a wild-type female CYP group, a wild-type male CYP group, a female negative control group and a male negative control group. Mice in the CYP groups were intraperitoneally injected with a single dose of 120 mg/kg CYP, and mice in the negative control groups were intraperitoneally injected with the same volume of normal saline. Subsequently, the phenotypic changes of the CIA model induced by CYP were continuously observed and photographed. Eleven 6-week-old SPF female C57BL/6J mice underwent bilateral ovariectomy (OVX group). Following successful surgery, these mice and five XY (Sry⁻) mice bred from Four Core Genotypes breeding stock were used to establish the chemotherapy-induced alopecia (CIA) model using the same protocol. Serum was collected from mice in the OVX group, wild-type female CYP group, and wild-type male CYP group on T7 after CYP administration for steroid hormone analysis by mass spectrometry to evaluate the effects of gonadal estrogen and sex chromosome background changes on the stability of the CYP-induced female alopecic phenotype. Finally, twenty SPF C57BL/6J mice aged 6-8 weeks (half male and half female) were randomly divided into a PTX low-dose group and a PTX high-dose group. On the 9th day after simultaneous hair removal, PTX was injected intraperitoneally at a single dose of 80 mg/kg or 120 mg/kg, respectively. Mice from the PTX low-dose group and the PTX high-dose group were continuously observed and photographed to compare the intra-group consistency of the phenotypes of female and male mice. Six SPF C57BL/6J mice (half male and half female) aged 6-8 weeks were used to repeat the construction method of the PTX low-dose group, and the hair follicle histological examination was performed at T0, T4, T7, T14 and T21, respectively, to observe the damage caused by PTX to hair follicle regeneration. ResultsThe phenotypes of CYP-induced male CIA mice are stable and reproducible. There are obvious individual differences in the alopecia phenotype in the CYP-induced female CIA model mice, which may be mainly caused by the differences in the relevant estrogens in the estrous cycle. The difference between OVX+CYP group and XY (Sry⁻) +CYP group disappeared, suggesting that ovarian-derived hormones and XY (Sry⁻) sex chromosome background may be involved in the formation of phenotypic heterogeneity of CYP-induced alopecia in female mice. The mice in the high-dose PTX group and the low-dose PTX group showed a relatively consistent alopecia and regrowth process, and there was no significant sex difference. ConclusionCYP-induced CIA is strongly influenced by sex, and ovariectomy or alteration of the sex chromosome background can improve the consistency of CYP-induced alopecic phenotypes in female mice. PTX-induced CIA shows good phenotypic consistency in both female and male mice, indicating broad applicability across sexes. Taken together, the choice of animal sex in CIA model construction, mechanistic studies, and evaluation of anti-alopecia interventions should take into account the type of chemotherapeutic agent, the study objective, and the required degree of phenotypic stability. Sex should therefore be considered an important variable in model standardization and interpretation of experimental findings.

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.

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 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.

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 study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.