A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

The impact of vedolizumab therapy on extraintestinal manifestations in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Extraintestinal manifestations (EIMs) pose a significant threat in inflammatory bowel disease (IBD) patients. Vedolizumab (VDZ) primarily affects the gastrointestinal tract. However, its impact on EIMs remains uncertain. Therefore, we conducted this meta-analysis to examine the effects of VDZ on EIMs during treatment. METHODS: Relevant studies were identified by conducting thorough searches across electronic databases, including PubMed, Ovid Embase, Medline, and Cochrane CENTRAL. Primary outcomes focused on the proportion of patients with resolution for pre-existing EIMs in IBD patients receiving VDZ. Secondary outcomes included the proportion of patients with EIM exacerbations and new onset EIMs during VDZ treatment. RESULTS: Our meta-analysis encompassed 21 studies. The proportion of patients with resolution of pre-existing EIMs in VDZ-treated IBD patients was 39% (150/386; 95% confidence interval [CI] 0.31-0.48). The proportion of patients with EIM exacerbations occurred at a rate of 28% (113/376; 95% CI 0.05-0.50), while new onset EIMs had a rate of 15% (397/2541; 95% CI 0.10-0.20). Subgroup analysis revealed a 40% (136/337) proportion of patients with resolution for articular-related EIMs and a 50% (9/18) rate for erythema nodosum. Exacerbation rates for arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, and aphthous stomatitis during VDZ use were 28% (102/328), 18% (7/38), and 11% (3/28), respectively. The incidence rate of newly developed EIMs during treatment was 11% (564/4839) for articular-related EIMs, with other EIMs below 2%. CONCLUSION: VDZ demonstrates efficacy in skin-related EIMs like erythema nodosum and joint-related EIMs including arthritis, arthralgia, spondyloarthritis, and peripheral joint diseases. Some joint and skin-related EIMs may experience exacerbation during VDZ therapy.

Infliximab-induced psoriasis in an ulcerative colitis patient successfully treated with guselkumab.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract. Tumor necrosis factor (TNF) inhibitors such as infliximab (IFX) are used to treat UC. But TNF inhibitors can induce psoriasis, which was characterized by IL-17/IL-22 expressing Th17 cells and IFN-γ expressing Th1 cells, with increased expression of Th17 cells correlated with more severe skin lesions and a need for Ustekinumab (UST) therapy1. UST is a monoclonal antibody that binds to the p40 subunit of the interleukin (IL)-12 and IL-23. It has shown remarkable efficacy in psoriasis and UC2. Guselkumab, a subcutaneously administered fully human IgG1 monoclonal antibody that selectively inhibits the p19 subunit of IL-23, is approved for the treatment of patients with moderate-to-severe plaque psoriasis3. It was shown to be efficacious in patients with prior failure of other biologics such as UST and was also observed in the treatment of psoriasis localized in difficult-to-treat body regions including the scalp, palms, soles, and fingernails. We report a case of successful use of guselkumab to treat a UC patient with IFX-induced psoriasis that was refractory to UST therapy.

Development and validation of a nomogram to predict non-response to 5-aminosalicylic acid in patients with ulcerative colitis.

BACKGROUND: there are some patients with ulcerative colitis (UC) who have non-response (NR) to 5-aminosalicylic acid (5-ASA). To promote individualized treatment in UC patients, it is crucial to identify valid predictors to estimate NR to 5-ASA. Therefore, this study aimed to identify the predictive value of clinical and biochemical markers and to construct a nomogram model predicting NR to 5-ASA in patients with UC. METHODS: data of patients diagnosed with UC in the First Hospital of China Medical University between January 2012 and December 2020 were retrospectively analyzed. Primary outcome was the proportion of NR to 5-ASA. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. RESULTS: of 284 UC patients who were treatment-naive, 86 (30.3 %) had NR to 5-ASA. Univariate regression analysis showed that disease classification (DC) (p = 0.008), monocytes (MONO) (p = 0.041), platelet distribution width (PDW) (p = 0.027), serum total cholesterol (TC) (p = 0.031) and α1 globulin (p < 0.001) were strongly associated with NR to 5-ASA. Receiver operating characteristics (ROC) analysis indicated the AUC was 0.852, it showed that this model has a good degree of discrimination. The DCA curve showed that the predicted probability is 0.0-96.0 %. CONCLUSION: this study developed a predictive model with good discrimination and calibration, and high clinical validity, which can effectively estimate the risk of NR to 5-ASA. DC, MONO, PDW, TC and α1 globulin can be used as predictors for NR to 5-ASA in UC patients.

[Clinical metabolomics of Zicuiyin in treatment of diabetic kidney disease].

This study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula. Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8). Both groups received routine chemical medicine treatment. In addition, the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks. The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, with the ethical approval No. 2017-023-01, and all the patients signed the informed consent form. The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP), 24 h urinary microalbumin(24hmAlb), urine albumin-to-creatinine ratio(UACR), and estimated glomerular filtration rate(eGFR) of the patients with 24hUP<3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP<3.5 g and subgroup B with 24hUP≥3.5 g). The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients. Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups, and their correlations with clinical indicators were analyzed. Zicuiyin lowered the levels of phenylalanine, pseudouridine, and adenosine [fold change(FC)<0.5, P<0.05] in subgroup A. The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels, and its targets were involved in phenylalanine metabolism and nucleoside metabolism.

[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Thioridazine protects against disturbed flow-induced atherosclerosis by inhibiting RhoA/YAP-mediated endothelial inflammation.

Atherosclerotic diseases remain the leading cause of adult mortality and impose heavy burdens on health systems globally. Our previous study found that disturbed flow enhanced YAP activity to provoke endothelial activation and atherosclerosis, and targeting YAP alleviated endothelial inflammation and atherogenesis. Therefore, we established a luciferase reporter assay-based drug screening platform to seek out new YAP inhibitors for anti-atherosclerotic treatment. By screening the FDA-approved drug library, we identified that an anti-psychotic drug thioridazine markedly suppressed YAP activity in human endothelial cells. Thioridazine inhibited disturbed flow-induced endothelial inflammatory response in vivo and in vitro. We verified that the anti-inflammatory effects of thioridazine were mediated by inhibition of YAP. Thioridazine regulated YAP activity via restraining RhoA. Moreover, administration of thioridazine attenuated partial carotid ligation- and western diet-induced atherosclerosis in two mouse models. Overall, this work opens up the possibility of repurposing thioridazine for intervention of atherosclerotic diseases. This study also shed light on the underlying mechanisms that thioridazine inhibited endothelial activation and atherogenesis via repression of RhoA-YAP axis. As a new YAP inhibitor, thioridazine might need further investigation and development for the treatment of atherosclerotic diseases in clinical practice.

Treatment of steroid-refractory immune checkpoint Inhibitor-induced intestinal pseudo-obstruction with infliximab.

Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a relatively new therapeutic approach for patients with several cancer types including non-small cell lung cancer1. Targeted monoclonal antibodies based drugs can activate anti-tumor immunity by blocking immune checkpoint receptors (CTLA-4, PD-1 receptor and its ligand PD-L1), in order to restore T-cell effector function2,3. However, the use of immune checkpoint inhibitors can lead to a unique side effect profile termed as immune-related adverse events (irAEs). Loss of T-cell inhibition results in an enhanced immune response driven by T-cell activation and is capable of inducing an autoimmune-related inflammation in normal tissue as a consequence of impaired self tolerance4. These irAEs can potentially involve every organ system including gastrointestinal, dermatologic, hepatic, and endocrine toxicities. For example, Fernandez-Gordon Sanchez et al reported a patient with immune-mediated colitis and nonimmune-mediated cholestasic injury induced by pembrolizumab that was successfully treated with Ustekinumab5. We report a steroid-refractory case of lung adenocarcinoma patient with an unusual irAE (intestinal pseudo-obstruction) during the treatment with immune checkpoint inhibitors that could be successfully managed by the administration of infliximab.

Successful treatment of Crohn's disease, aseptic liver abscess and psoriasis with ustekinumab.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is commonly known to affect the ileum and colon. Aseptic abscess (AA) has been pathologically described as sterile abscess with a predominance of polymorphonuclear leucocyte infiltrates, and is considered a rare extraintestinal manifestation of CD. AA presents a great challenge to physicians in determining if it is an extraintestinal manifestation of CD or an actual infection with pathogenic microorganisms. There is a strong association between CD and psoriasis. But the coexistence of AA and psoriasis in CD was unusual. Ustekinumab, as an IL 12/23 inhibitor, is the only treatment with a similar mechanism currently available for both CD and psoriasis. We report a case of successful use of ustekinumab to treat a CD patient with hepatic AA and psoriasis.

Reply: SARS-CoV-2 vaccination in inflammatory bowel disease patients with different biological agents.

We thank Dr Mungmunpuntipantip and colleague for their interest and thoughtful comments on our publication. The authors have highlighted several important considerations for the impact of SARS-CoV-2 vaccination in inflammatory bowel disease (IBD) patients with different biological agents. We fully agree with the author's point of view, and we also point out the limitations in our meta-analysis.

Impact of SARS-CoV-2 vaccination in inflammatory bowel disease patients with different biological agents: a systematic review and meta-analysis.

BACKGROUND: There are concerns regarding the effect of biological agents on SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD). A systematic review and meta-analysis was performed about the serological responses, breakthrough infections and clinical relapse of IBD patients treated with biological agents following SARS-CoV-2 vaccination. METHODS: Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled seroconversion rates, breakthrough infection rates and clinical relapse rates after SARS-CoV-2 vaccination in IBD patients treated with biological agents. Secondary outcomes were the comparison of seroconversion rates, breakthrough infection rates and clinical relapse rates in IBD patients treated with biological agents and control cohort after SARS-CoV-2 vaccination. RESULTS: Thirty-five studies were included in this meta-analysis. A high percentage of seroconversion (96.6%, 99% and 99.2%) was achieved in IBD patients treated with anti-TNF-α therapy, vedolizumab and ustekinumab after SARS-CoV-2 vaccination, respectively. The pooled breakthrough infection rate was 2.5% and 3.9% in IBD patients treated with anti-TNF-α therapy and vedolizumab, respectively. The breakthrough infection rate in IBD patients treated with anti-TNF-α therapy was significantly lower than control cohort (RR 0.178, 95% CI 0.084-0.378). The pooled clinical relapse rate in IBD patients treated with anti-TNF-α therapy, vedolizumab and ustekinumab was 6.9%, 5.4% and 5.3%, respectively. CONCLUSION: The overall seroconversion rate after SARS-CoV-2 vaccination in IBD patients treated with biological agents is high. The overall breakthrough infection rate and clinical relapse rate in IBD patients treated with biological agents were low.

Long-term clinical outcomes after the discontinuation of anti-TNF agents in patients with inflammatory bowel disease: a meta-analysis.

BACKGROUND: there are concerns regarding the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). A systematic review and meta-analysis were performed to evaluate the risk of relapse after discontinuation of anti-TNF agent in patients, and the response to retreatment with the same anti-TNF agent. METHODS: electronic databases were searched to identify relevant studies. Primary outcomes were the pooled percentage of relapses after the withdrawal of anti-TNF agents. Secondary outcomes were the pooled percentage of the response to retreatment with the same anti-TNF agent after relapse. RESULTS: thirty-seven studies were included in this meta-analysis. The overall risk of relapse after discontinuation of anti-TNF agent was 43 % for ulcerative colitis (UC) and 43 % for Crohn's disease (CD). In UC, the relapse rate was 37 % at 1-2 year, and 58 % at 3-5 years. In CD, the relapse rate was 38 % at 1-2 year, 53 % at 3-5 years, and 49 % at more than five years. When clinical remission was the only criterion for stopping anti-TNF agent, the relapse rate was 42 % in UC and 45 % in CD, which decreased to 40 % in UC and 36 % in CD when clinical remission and endoscopic healing were required. Retreatment with the same anti-TNF agent induced remission again in 78 % of UC patients and 76 % of CD patients. CONCLUSION: our meta-analysis showed that a high proportion of IBD patients will relapse after discontinuation of anti-TNF agent. The response to retreatment with the same anti-TNF agent is generally favorable in patients who relapse.

Effectiveness of 4 L, 2 L, and 1 L PEG bowel preparation for colonoscopy in patients with ulcerative colitis: a retrospective study.

An adequate bowel preparation (BP) is essential for a high quality colonoscopy. Patients with ulcerative colitis (UC) show low compliance with BP due to the large volume of lavage solution to be ingested. We sought to evaluate the efficacy of 4 L, 2 L, and 1 L polyethylene glycol (PEG) for BP and identify the related factors of suboptimal BP (SOBP) in patients We conducted a retrospective analysis of UC patients who underwent colonoscopies from January 2017 to March 2022 at our hospital. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS). BBPS score ≤ 6 is considered SOBP. The related factors associated with SOBP were evaluated using logistic regression analyses. In total, 282 patients with UC were enrolled in our study. The bowel cleansing by BBPS was 8.44±0.84 in 4 L PEG-based BP, 8.29±0.95 in 2 L PEG-based BP, and 7.59±1.17 in 1 L PEG-based BP. On multivariable analysis, extensive colitis (E3), moderate disease activity (mayo score: 6-10) to severe disease activity (mayo score: 11-12), severe endoscopic activity (EMS: 3), biological therapies (infliximab and vedolizumab), and 1 L PEG-based BP were associated with an increased odds of SOBP. Our study demonstrated that 2 L-based and 4 L-based BP is highly effective in UC patients undergoing colonoscopy. Moderate to severe disease activity, severe endoscopic activity, and the use of biological therapies were associated with an increased risk of SOBP in UC patients undergoing colonoscopy.

Cultivation of compound ability of postgraduates with medical professional degree: the importance of double tutor system.

As we all know, medical postgraduate education is very important for training high-quality clinicians, and can have a long-term impact on the promotion of the global health service system. In recent years, following the example of developed countries in Europe and America, the Chinese government has reformed the training mode of medical postgraduates and implemented the double tutor system. Although this system will bring many positive effects in theory, the difficulties encountered in implementing this system are real and need the joint efforts of schools, tutors and students to solve them. This article closely follows the background of the current era, compares the differences between Chinese and foreign graduate training modes, and emphatically discusses the significance and problems of the double tutor system in the postgraduate education reform in China.

Pharmacological effects of Eleutherococcus senticosus on the neurological disorders.

Eleutherococcus senticosus is a medicinal plant widely used in traditional medicine and edible remedies with effects on anti-fatigue, sleep improvement, and memory enhancement. Recently, the application of E. senticosus to neurological disorders has been a focus. However, its overall pharmacological effect on neural diseases and relevant mechanisms are needed in an in-depth summary. In this review, the traditional uses and the therapeutic effect of E. senticosus on the treatment of fatigue, depression, Alzheimer's disease, Parkinson's disease, and cerebral ischemia were summarized. In addition, the underlying mechanisms involved in the anti-oxidative damage, anti-inflammation, neurotransmitter modulation, improvement of neuronal growth, and anti-apoptosis were discussed. This review will accelerate the understanding of the neuroprotective effects brought from the E. senticosus, and impetus its development as a phytotherapy agent against neurological disorders.

Dual biologic therapy for severe ulcerative colitis, concomitant extraintestinal manifestations and an orbital osteoma: a successful treatment.

It is difficult to manage UC patients with tumor and extraintestinal manifestations (EIMs). We present this case of acute severe UC patient with peripheral arthritis and orbital tumor could be successfully managed by the concomitant use of two biologics (Dual targeted therapy, DTT) including vedolizumab (VDZ) and ustekinumab (UST). VDZ is approved for the treatment of patients with moderate-to-severe UC, but might have limited efficacy in treating EIMs due to its gut specific mechanism. UST shows clinical efficacy in the treatment of EIMs and is used for UC treatment.

[Mechanism of Zicui Decoction in treatment of diabetic kidney disease based on network pharmacology and molecular docking].

This study aimed to explore the potential mechanism of Zicui Decoction in the treatment of diabetic kidney disease(DKD) based on network pharmacology and molecular docking. The DKD-related targets were searched from DrugBank, Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man Database(OMIM), GeneCards, DisGeNET, Comparative Toxico-genomics Database(CTD), and PharmGKB. The targets of the serum active ingredients of Zicui Decoction were predicted from the SwissTargetPrediction. The obtained results were then mapped to harvest the potential targets of Zicui Decoction against DKD. Cytoscape 3.8.2 was employed to construct the "serum active ingredient of Zicui Decoction-potential target-DKD" network. The protein-protein interaction(PPI) network was constructed using the STRING. The key targets were then subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis using the DAVID V6.8 for uncovering its action mechanims. The serum active ingredients of Zicui Decoction were then docked to the core terget proteins with PyMOL and AutoDock Vina. The results of network analysis showed that there were 173 targets associated with 12 serum active ingredients and 6 756 targets related to DKD. The mapping revealed 124 potential targets, of which 26 were the key targets of Zicui Decoction against DKD and 3 were the core teargets. GO analysis yielded 34 entries(P≤0.01 and benjamini≤0.01), and in the treatment of DKD with Zicui Decoction, such biological processes as ERK cascade, regulation of apoptosis, proliferation and migration, and regulation of fibroblast proliferation and ligand receptor binding were involved. According to the KEGG analysis, 19 signaling pathways(P≤0.01 and benjamini≤0.01) were screened out, among which the PI3 K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and VEGF signaling pathway were closely associated with DKD. Molecular docking verified a good binding ability of the three serum active ingredients to the core targets. In conclusion, Zicui Decoction alleviates DKD possibly by inhibiting inflammation, regulating autophagy, and anti-fibrosis.

Rice root exudates enhance desorption and bioavailability of phthalic acid esters (PAEs) in soil associating with cultivar variation in PAE accumulation.

Phthalic acid esters (PAEs) is a class of prevalent pollutants in agricultural soil, threating food safety through crop uptake and accumulation of PAEs. Accumulation of PAEs varies largely among crop species and cultivars. Nevertheless, how root exudates affect PAE bioavailability, dissipation, uptake and accumulation is still not well understood. In the present study, desorption and pot experiments were designed to investigate how root exudates from high-(Peizataifeng) and low-(Fengyousimiao) PAE accumulating rice cultivars affect soil PAE bioavailability, dissipation, and accumulation variation. Rice root exudates including low molecular weight organic acids (LMWOAs) of Peizataifeng and Fengyousimiao could enhance desorption of two typical PAE compounds, di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP), from aged soil to their available fractions by increasing soil dissolved organic carbon (DOC), thus improving their bioavailability in soil. Peizataifeng produced twice higher amounts of oxalic acid, critic acid and malonic acid in root exudates, and exhibited stronger effects on enhancing desorption and bioavailability of DBP and DEHP than Fengyousimiao. Higher (by about 50%) total organic carbon contents of root exudates from Peizataifeng led to higher (by 10-30%) soil microbial biomass carbon and nitrogen than Fengyousimiao, and thus promoted more PAE dissipation from soil than Fengyousimiao. Nevertheless, higher (by 20-50%) soil DOC and significantly higher PAE bioavailability in the soils planted Peizataifeng resulted in greater (by 53-93%) PAE accumulation in roots and shoots of Peizataifeng than Fengyousimiao, confirming by higher (by 1.82-3.48 folds) shoot and root bioconcentration factors of Peizataifeng than Fengyousimiao. This study reveals that the difference in root exudate extent and LMWOAs between Peizataifeng and Fengyousimiao differentiates PAE accumulation.