Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Objective:To explore the repairing effect and mechanism of tangeretin in rats with spinal cord injury.Methods:The rats were divided into sham-operation group, model group and tangeretin group according to random number table, with 8 rats in each group. Except for the sham-operation group, Allen hit method was used to make rat models in the other groups. After the model was successfully established, the tangeretin group was intragastrically administered with tangeretin 50 mg/kg, and the sham-operation group and the model group were intragastrically administered with an equal volume of normal saline once a day for 14 days. On days 0, 3, 7, and 14 after modeling, the motor function recovery of rats was assessed using the Basso-Beattie-Bresnahan (BBB) score; the morphological changes of the spinal cord tissues were observed using HE staining and Nissl staining; the SOD and GSH activities and MDA, IL-1β, TNF-α, and IL-10 levels in the spinal cord tissues of rats in each group were measured using ELISA kit detection; the GFAP and Neun expressions in the spinal cord tissues were detected by immunofluorescence; the IL-1β, TNF-α, IL-10, nuclear factor E2-related factor 2 (Nrf-2), and NAD (P) H-quinone oxidoreductase 1 (NQO-1) expressions in the spinal cord tissues were detected by Western blot.Results:Compared with the model group, the BBB score increased in the tangeretin group ( P<0.05), HE staining score decreased ( P<0.05), and the number of Nissl bodies increased ( P<0.05); the level of IL-10, SOD and GSH activities increased ( P<0.05), and IL-1β, TNF-α and MDA levels decreased in the spinal cord tissue ( P<0.05); GFAP fluorescence intensity decreased ( P<0.05) and NeuN fluorescence intensity increased ( P<0.05); the relative expression of IL-1β and TNF-α decreased ( P<0.05), and the relative expressions of IL-10, Nrf-2 and NQO-1 protein increased ( P<0.05). Conclusions:Tangeretin can exert anti-inflammatory and anti-oxidative stress effects through the Nrf2/NQO1 signaling pathway and alleviate early spinal cord injury in rats. On the other hand, it may promote the recovery of spinal cord injury by reducing glial scar generation and promoting neural cellogenesis.

Objective To explore the enhancement pattern and characterization of hepatic hemangionmas with contrast enhanced ultrasound (CEUS).Methods A total of 44 patients with 49 nodules preliminary diagnosed of liver hemangioma were included in this study.For each nodule,the enhancement pattern,level,and dynamic change of CEUS were evaluated,and the features of hemangionmas were groups as echoic and compared with those on CEUS.Results All hemangiomas enhanced in arterial phase with centripetal progression in venous and late phase on CEUS,among which 41 lesions showed peripheral nodular enhancement while 8 showed peripheral rim-like enhancement.The whole-tumor enhancement pattern was seen in 13 lesions and part-tumor enhancement was shown in 36 lesions.The performance of part-tumor was independent of tumor echoic and hypoechoic tumors mostly presented to be whole tumor enhancement pattern.During portal venous and late phase,42 lesions showed hyperenhancement,while 7 lesions showed isoenhancement.Conclusions CEUS can suggest the enhancement dynamic characters of hepatic giant hemangionmas and reveals the relationship of grey-scale echoic and enhancement pattern of hemangiomas.It is important to diagnose the hepatic giant hemangionmas for CEUS.

OBJECTIVE:To establish a method for the qualitative identification and content determination of berberine hydro-chloride in Huangjin paste. METHODS:TLC was adopted for the qualitative identification of berberine hydrochloride and HPLC was conducted for the content determination of berberine hydrochloride in preparation. The column was Symmetry Shield Rp-18 with mobile phase of acetonitrile-0.1% phosphoric acid(50∶50,V/V)at a flow rate of 1.0 ml/min,detection wavelength was 265 nm,column temperature was 30 ℃ and injection volume was 10 μl. RESULTS:TLC spots of berberine hydrochloride in prepara-tion were clear and well-separated. The linear range of berberine hydrochloride was 2.5-20.0 μg/ml(r=0.999 0);RSDs of preci-sion,stability and reproducibility tests were lower than 3%;recovery was 97.7%-102.1%(RSD=1.68%,n=6). CONCLUSI-ONS:The method is simple,accurate and reproducible,and can be used for the qualitative identification and content determination of berberine hydrochloride in Huangjin paste.