Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

Congenital coagulation factor Ⅶ deficiency is a rare autosomal incomplete recessive disorder caused by a defect in the coagulation factor Ⅶ (FⅦ) gene, with an incidence of approximately 1 in 500 000. Antiphospholipid antibody syndrome is relatively common and is a common cause of acquired thrombosis. However, the combination of the latter and the former is extremely rare in clinical practice, which brings difficulties to diagnosis and treatment. This article reported the laboratory examination, diagnosis and treatment of a patient with congenital coagulation factor Ⅶ deficiency and antiphospholipid syndrome after portal vein thrombosis, and reviewed the relevant literature.

Objective To observe the effects of 3 different nutritional support modes of nasogastric tube nutrition,nasoenteric tube nutrition and nasoenteric tube combined with nasogastric tube nutrition on the biliary-related indices of critically ill patients.Methods The observational research method was conducted,the patients admitted to the department of intensive care unit(ICU)of Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)from June 2023 to May 2024 serving as the subjects of the study.The subjects were divided into three groups,namely the nasogastric tube group(indwelling nasogastric tube for enteral nutrition),the nasoenteric tube group(indwelling nasoenteric tube for enteral nutrition),and the mixed nutrition group(indwelling nasoenteric tube combined with naso-gastric tube for enteral nutrition)according to the different modes of enteral nutrition given.The clinical data of the patients was collected,including gender,age,previous underlying diseases,nutritional risk screening 2002(NRS2002)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ),gallbladder volume,data on laboratory-related indices,and prognosis during hospitalisation.Compare the differences between the observed indicators and their change values before and after the initiation of enteral nutrition within each group;analyse the correlation between gallbladder volume and other observed indicators using Spearman's correlation analysis;screen the influencing factors of gallbladder volume using univariate regression analysis;screen the influencing factors of ICU patients'survival during hospitalisation using multifactorial Logistic regression analysis,and plot the receiver operator characteristic curve(ROC curve)of the subjects to analyse the predictive value of each influencing factor on patients'prognosis.Results A total of 141 patients who met the inclusion criteria were included in the study,comprising 54 cases in the nasogastric tube group,38 cases in the nasoenteric tube group,and 49 cases in the mixed nutrition group.Of the patients who survived during ICU hospitalization,105 survived,while 36 died,mortality was 25.53%.① No statistically significant differences were observed in the comparison of gender,age,previous underlying disease,NRS2002 score,and APACHEⅡscore among the enrolled groups.② A comparative analysis was conducted on the biliary-related indexes of the nasogastric tube and nasoenteric tube groups before and after the initiation of enteral nutrition.The results revealed no statistically significant differences between the two groups.On the 7th day of enteral nutrition initiation,the gallbladder volume of the nasoenteric tube group was found to be significantly larger than the gallbladder volume on the 1st day(cm3:28.00±6.36 vs.25.20±4.75,P<0.05).In the mixed nutrition group,the gallbladder volume on the initiation of enteral nutrition on day 7 was significantly smaller than that on the 1st day of initiating enteral nutrition(cm3:25.03±4.69 vs.28.68±5.96,P<0.05).③A comparative analysis was conducted among the three groups,revealing significant variations in the values of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),indirect bilirubin(IBil),alkaline phosphatase(ALP),γ-glutamyltranspeptidase(γ-GT),and gallbladder volume across the groups.From 1-7 days following the initiation of enteral nutrition,the bile-related indexes in the nasoenteric tube group exhibited an increasing trend,while the bile-related indexes in the mixed nutrition group demonstrated a decreasing trend.④ Spearman correlation analysis showed that gallbladder volume was significantly and positively correlated with AST,ALT,ALP,and γ-GT(r values of 0.398,0.299,0.242,and 0.262,respectively,all P<0.01).⑤ Multivariate Logistic regression analysis demonstrated that the initiation of enteral nutrition for 7 days was associated with a significant advantage,as indicated by an odds ratio(OR)of 1.031,with a 95%confidence interval(95%CI)of 1.004-1.058,and a P value was 0.024.Furthermore,the initiation of enteral nutrition for 7 d AST(OR=1.031,95%CI was 1.004-1.058,P=0.024),TBil(OR=1.187,95%CI was 1.039-1.355,P=0.011),and IBil(OR=0.707,95%CI was 0.542-0.921,P=0.010),and γ-GT(OR=0.985,95%CI was 0.972-0.999,P=0.034)were all factors affecting the survival of ICU patients during hospitalisation.Conclusions In the context of patients receiving intensive care,the prolonged utilisation of nasoenteric feeding tubes for a duration exceeding seven days has been observed to potentially induce an augmentation in gallbladder volume and an elevation in biliary-related indices,including ALT,AST,ALP,and γ-GT.The concomitant administration of nasogastric feeding,grounded in the foundation of simple nasoenteric tube nutrition,has been demonstrated to result in a reduction of these biliary-related indices to a certain extent.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM.

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

OBJECTIVE: In Pakistan, traditional medicines are an important component of the medical system, with numerous varieties and great demands. However, due to the scattered resources and the lack of systematic collection and collation, adulteration of traditional Pakistani medicine (TPM) is common, which severely affects the safety of their medicinal use and the import and export trades. Therefore, it is urgent to systematically organize and unify the management of TPM and establish a set of standards and operable methods for the identification of TPM. METHODS: We collected and organized the information on 128 TPMs with regard to their medicinal parts, efficacy, usage, and genetic material, based on Pakistan Hamdard Pharmacopoeia of Eastern Medicine: Pharmaceutical Codex. The genetic information of TPM is summarized from national center for biotechnology information (NCBI) and global pharmacopoeia genome database (GPGD). Furthermore, we utilized bioinformatics technology to supplement the chloroplast genome (cp-genome) data of 12 TPMs. To build the web server, we used the Linux + Apache + MySQL + PHP (LAMP) system and constructed the webpage on a PHP: Hypertext Preprocessor (PHP) model view controller (MVC) framework. RESULTS: We constructed a new genomic database, the traditional Pakistani medicine genomic database (TPMGD). This database comprises five entries, namely homepage, medicinal species, species identification, basic local alignment search tool (BLAST), and download. Currently, TPMGD contains basic profiles of 128 TPMs and genetic information of 102 TPMs, including 140 cytochrome c oxidase subunit I (COI) sequences and 119 mitochondrial genome sequences from Bombyx mori, 1 396 internal transcribed spacer 2 (ITS2) sequences and 1 074 intergenic region (psbA-trnH) sequences specific to 92 and 83 plant species, respectively. Additionally, TPMGD includes 199 cp-genome sequences of 82 TPMs. CONCLUSION TPMGD is a multifunctional database that integrates species description, functional information inquiry, genetic information storage, molecular identification of TPM, etc. The database not only provides convenience for TPM information queries but also establishes the scientific basis for the medication safety, species identification, and resource protection of TPM.

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.