Urinary protein quantification is critical for assessing the severity of chronic kidney disease (CKD). However, the current procedure for determining the severity of CKD is completed through evaluating 24-h urinary protein, which is inconvenient during follow-up. To quickly predict the severity of CKD using more easily available demographic and blood biochemical features during follow-up, we developed and compared several predictive models using statistical, machine learning and neural network approaches. The clinical and blood biochemical results from 551 patients with proteinuria were collected. Thirteen blood-derived tests and 5 demographic features were used as non-urinary clinical variables to predict the 24-h urinary protein outcome response. Nine predictive models were established and compared, including logistic regression, Elastic Net, lasso regression, ridge regression, support vector machine, random forest, XGBoost, neural network and k-nearest neighbor. The AU-ROC, sensitivity (recall), specificity, accuracy, log-loss and precision of each of the models were evaluated. The effect sizes of each variable were analysed and ranked. The linear models including Elastic Net, lasso regression, ridge regression and logistic regression showed the highest overall predictive power, with an average AUC and a precision above 0.87 and 0.8, respectively. Logistic regression ranked first, reaching an AUC of 0.873, with a sensitivity and specificity of 0.83 and 0.82, respectively. The model with the highest sensitivity was Elastic Net (0.85), while XGBoost showed the highest specificity (0.83). In the effect size analyses, we identified that ALB, Scr, TG, LDL and EGFR had important impacts on the predictability of the models, while other predictors such as CRP, HDL and SNA were less important. Blood-derived tests could be applied as non-urinary predictors during outpatient follow-up. Features in routine blood tests, including ALB, Scr, TG, LDL and EGFR levels, showed predictive ability for CKD severity. The developed online tool can facilitate the prediction of proteinuria progress during follow-up in clinical practice.

Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. Short-term, 16-week treatment period. Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Background: Mounting studies have shown that hyperuricemia is related to kidney diseases through multiple ways. However, the application of urinary uric acid indicators in patients with reduced renal function is not clear. In this study, we aim to determine the effects of renal function on various indicators reflecting uric acid levels in patients with chronic kidney disease (CKD). Methods: Anthropometric and biochemical examinations were performed in 625 patients with CKD recruited from Dept of Nephrology of Huadong hospital affiliated to Fudan University. Multiple regression analyses were used to study correlations of the estimated glomerular filtration rate (eGFR) with serum uric acid (SUA) and renal handling of uric acid. For further study, smooth curve plots and threshold effect analyses were applied to clarify associations between renal function and uric acid levels. Results: The nonlinear relationships were observed between eGFR and urinary uric acid indicators. The obvious inflection points were observed in smooth curve fitting of eGFR and fractional excretion of uric acid (FEur), excretion of uric acid per volume of glomerular filtration (EurGF). In subsequent analyses where levels of eGFR< 15 mL/min/1.73m² were dichotomized (CKD5a/CKD5b), patients in the CKD5a showed higher levels of FEur and EurGF while lower levels of urinary uric acid excretion (UUA), clearance of uric acid (Cur) and glomerular filtration load of uric acid (FLur) compared with CKD5b group (all P < 0.05). And there was no significant difference of SUA levels between two groups. On the other hand, when eGFR< 109.9 ml/min/1.73 m² and 89.1 ml/min/1.73 m², the resultant curves exhibited approximately linear associations of eGFR with Cur and FLur respectively. Conclusion: FEur and EurGF showed significantly compensatory increases with decreased renal function. And extra-renal uric acid excretion may play a compensatory role in patients with severe renal impairment to maintain SUA levels. Moreover, Cur and FLur may be more reliable indicators of classification for hyperuricemia in CKD patients.

Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD < 8%. Differential proteins are mainly related to cell cycle, cell proliferation, DNA replication, RNA splicing and apoptosis. Abberant binding function, catalysis activity and transportor activity of differential proteins might contribute to the malignant transformation of OLK. Of the 34 identified differential proteins with RSD < 8%, 13 novel cancer-related proteins were reported in the present study. This study might provide a new insight into the mechanism of OLK malignant transformation and the potent biomarkers for early diagnosis, meanwhile further facilitate the application of the quantification proteomics to carcinogenesis research.

Increasing evidence has shown that albuminuria is related to serum uric acid. Little is known about whether this association may be interrelated via renal handling of uric acid. Therefore, we aim to study urinary uric acid excretion and its association with albuminuria in patients with chronic kidney disease (CKD). A cross-sectional study of 200 Chinese CKD patients recruited from department of nephrology of Huadong hospital was conducted. Levels of 24 h urinary excretion of uric acid (24-h Uur), fractional excretion of uric acid (FEur) and uric acid clearance rate (Cur) according to gender, CKD stages, hypertension and albuminuria status were compared by a multivariate analysis. Pearson and Spearman correlation and multiple regression analyses were used to study the correlation of 24-h Uur, FEur and Cur with urinary albumin to creatinine ratio (UACR). The multivariate analysis showed that 24-h Uur and Cur were lower and FEur was higher in the hypertension group, stage 3–5 CKD and macro-albuminuria group (UACR> 30 mg/mmol) than those in the normotensive group, stage 1 CKD group and the normo-albuminuria group (UACR< 3 mg/mmol) (all P < 0.05). Moreover, males had higher 24-h Uur and lower FEur than females (both P < 0.05). Multiple linear regression analysis showed that UACR was negatively associated with 24-h Uur and Cur (P = 0.021, P = 0.007, respectively), but not with FEur (P = 0.759), after adjusting for multiple confounding factors. Our findings suggested that urinary excretion of uric acid is negatively associated with albuminuria in patients with CKD. This phenomenon may help to explain the association between albuminuria and serum uric acid.

Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA).Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression.Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro.Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA.