This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

The extraction process of traditional Chinese medicine(TCM) is an important part in the production and processing of TCM products. The modeling of this process is of great significance for achieving intelligent production. This paper summarizes the modeling methods for the extraction process of TCM, which mainly include mechanism modeling, empirical formula modeling, data-driven modeling, and mixed modeling. Among them, mechanism modeling and data-driven modeling are widely used. Furthermore, this paper suggests that the future research on the modeling of the extraction process of TCM can be carried out from the following five aspects: in-depth research and development of the extraction process of TCM compound prescriptions, complete description of the whole extraction process of TCM, development of methods for accurate determination of the properties of TCM decoction pieces before extraction, development of adaptive self-optimization technology for models, and construction of models based on a new generation of artificial intelligence methods.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Models, Theoretical ; Artificial Intelligence ; Humans

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Peripheral artery disease(PAD),commonly encountered in vascular surgery,predominantly affects the lower limbs and presents with ischemic symptoms resulting from atherosclerosis.It carries risks of adverse limb events and cardiovascular events.Antithrombotic therapy remains a cornerstone in the management of PAD.This article reviews the evidence and research progress regarding dual-pathway antithrombotic therapy for PAD.Multiple clinical trials have demonstrated that,compared to single antiplatelet therapy,dual-pathway antithrombotic therapy significantly reduces the risks of major adverse limb events and major adverse cardiovascular events without a significant increase in bleeding risk.For high-risk patients,such as those with advanced age,multivessel disease,comorbid coronary artery disease,or those undergoing endovascular revascularization,the benefits of dual-pathway antithrombotic therapy are particularly pronounced.Current clinical guidelines have incorporated dual-pathway antithrombotic therapy into their recommendations,standardized criteria for identifying the most appropriate patient populations remain lacking.Despite its advantages in reducing adverse events,its long-term safety profile and optimal target populations warrant further investigation.

Yigongsan， derived from QIAN Yi’s Key to Therapeutics of Children’s Diseases in the Song Dynasty， is a classic pediatric prescription that is included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine in 2022. This paper verifies and analyzes the historical origin， composition， dosage， processing， decoction method and efficacy of Yigongsan by systematically combing ancient books and modern documents. As a result， Yigongsan is composed of five herbs： Panax ginseng， Poria cocos， Atractylodes macrocephala， Citrus reticulata and Glycyrrhiza uralensis， of which P. cocos should be peeled， A. macrocephala is fried with soil， G. uralensis is roasted with honey while P. ginseng and C. reticulata are raw products. According to the dosage of ancient and modern times， each medicinal herb must be ground into fine powder， 1.6 g for each， added with 300 mL of water， 5 pieces of Zingiber officinale， and 2 Ziziphus jujuba， decocted together to 210 mL， and taken before meals. In ancient books， Yigongsan is used to treat vomiting， diarrhea， spleen and stomach deficiency， chest and abdominal distension， and lack of appetite， etc. Modern research showed that Yigongsan could also be used in the diseases of immune system， respiratory system， blood system， etc.， involving infantile anorexia， asthma， anemia， tumors and so on.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:To establish a prediction method of diopter based on sequence of ocular biological parameters.Methods:A stratified random cluster sampling method was used to extract the dataset. The dataset consisted of data collected from January 2022 to January 2023 by the Eye & ENT Hospital, Fudan University, from children aged 5 to 13 years in 2 key schools and 2 general schools of Yangpu District, Shanghai. Children’s ocular biological parameters, including sex, age, diopter, axial length, corneal curvature, and anterior chamber depth were collected. The slope of the optimally fitted straight line was calculated using the least squares method. The least square-back propagation (BP) neural network model was established by combining baseline data and the pre-processed rate of the change of ocular biological parameters. The dataset was divided into the training set and the validation set according to the ratio of 8:2 for five-fold cross-validation. The model performance was evaluated by using the mean absolute error (MAE), mean squared error (MSE), root mean square error (RMSE), correlation coefficient R, and coefficient of determination R2. Results:The optimal performances of R2, R, RMSE, MAE, and MSE of the least square-BP neural network model were 0.96, 0.981 9, 0.214 2, 0.139 9 D, 0.045 9, respectively. The regression equation between the predicted value and the true value of the diopter was y=0.97 x+ 0.014 8, R2=0.97, with good correlation. In the internal verification, MAE values of the diopter at three, six, nine, and twelve months of follow-up were 0.110 1, 0.136 0, 0.153 7, and 0.184 8 D, respectively, which achieved clinically acceptable performance (less than 0.25 D). In the external validation, the errors were less than 0.25 D at all ages. Conclusions:A prediction method of diopter based on sequence of ocular biological parameters was successfully developed.