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 evaluate the value of S-Detect technology of ultrasonography in the diagnosis of thyroid tumors. Methods Ninety-three thyroid tumors in 93 patients were enrolled in the group.A varied image features of the thyroid masses in gray-scale ultrasonography were analyzed by S-Detect technology and experienced doctor separately.The results were compared and the diagnostic ability were also compared between the two methods. Results There were 44 malignant tumors and 49 benign tumors in these thyroid nodules.The sensitivity of S-Detect technology in the diagnosis of thyroid malignant tumors was higher,up to 88.7%. In the five image features of the thyroid tumors in gray-scale ultrasonography,the result of composition of the mass obtained by S-Detect was the most consistent with that of the doctors and Kappa value was 0.89.Conclusions S-Detect is a kind of computer-aided diagnosis system,which is suitable for the ultrasound beginners in the diagnosis of thyroid tumors.

Objective To observe and analyze the effects of transcutaneous electrical acupoint stimulation (TEAS) combined withparaffin therapy on hand function and limb rehabilitation in patients with hemiplegia after stroke.Methods A total of 162 patients with hemiplegia complicated with hand dysfunction after stroke were selected as the research subjects and randomly divided into the observation group and the control group,81 cases in each group.The patients in the control group were treated with routine rehabilitation training and paraffin therapy for rehabilitation treatment,while the patients in the observation group were treated with TEAS treatment on the basis of the control group.The indexes of hand function such as Fugl-Meyer motor assessment upper extremity (FMA-UE) score,the wrist flexor modified Ashworth scale (MAS) score,the hand movement function score before and after the treatment were evaluated and compared.The Wolf motor function test (WMFT) score,the modified Barthel index (MBI) score,the national institutes of health stroke scale (NIHSS) score before and after the treatment were evaluated and compared.The therapeutic effects of the two groups were evaluated and compared.Results After the treatment,the FMA-UE score and the hand movement function score of the observation group were significantly higher than those of the control group,and the wrist flexor MAS score was significantly higher than that the control group(P<0.05). The WMFT score and the MBI score of the observation were significantly higher than those of the control group,and the NIHSS score was significantly lower than the control group (P<0.05).The clinical efficiencies of the observation group and the control group were 90.1% and 69.1% respectively,and there was significant differences between the two groups (P<0.05).Conclusion The application of TEAS combined with paraffin therapy in treatment and rehabilitation of patients with stroke can improve the hand function,promote the rehabilitation of limb movement function,and improve the quality of life and therapeutic effects.

Objective To observe and analyze the effects of transcutaneous electrical acupoint stimulation (TEAS) combined withparaffin therapy on hand function and limb rehabilitation in patients with hemiplegia after stroke.Methods A total of 162 patients with hemiplegia complicated with hand dysfunction after stroke were selected as the research subjects and randomly divided into the observation group and the control group,81 cases in each group.The patients in the control group were treated with routine rehabilitation training and paraffin therapy for rehabilitation treatment,while the patients in the observation group were treated with TEAS treatment on the basis of the control group.The indexes of hand function such as Fugl-Meyer motor assessment upper extremity (FMA-UE) score,the wrist flexor modified Ashworth scale (MAS) score,the hand movement function score before and after the treatment were evaluated and compared.The Wolf motor function test (WMFT) score,the modified Barthel index (MBI) score,the national institutes of health stroke scale (NIHSS) score before and after the treatment were evaluated and compared.The therapeutic effects of the two groups were evaluated and compared.Results After the treatment,the FMA-UE score and the hand movement function score of the observation group were significantly higher than those of the control group,and the wrist flexor MAS score was significantly higher than that the control group(P<0.05). The WMFT score and the MBI score of the observation were significantly higher than those of the control group,and the NIHSS score was significantly lower than the control group (P<0.05).The clinical efficiencies of the observation group and the control group were 90.1% and 69.1% respectively,and there was significant differences between the two groups (P<0.05).Conclusion The application of TEAS combined with paraffin therapy in treatment and rehabilitation of patients with stroke can improve the hand function,promote the rehabilitation of limb movement function,and improve the quality of life and therapeutic effects.

Objective To explore the diagnostic value of contrast-enhanced ultrasonography (CEUS) in ureteral lesions.Methods The ultrasonogram of conventional ultrasound and CEUS were retrospectively analyzed in 19 confirmed ureteral lesions cases by operation and pathology.The size,inner echoes,boundary and color blood signal of ureteral lesions were observed by conventional ultrasound.The modality and phases of enhancement,including arrival time,peak time,washout time and appearance of internal structure,were observed by CEUS.Results The 19 ureteral tumors were of maximum widths between 2.1 to 7.7 cm.Conventional ultrasound showed 7 hypoechoic masses,10 isoechoic masses,1 hyperechoic mass and 1 unclear mass.Color Doppler flow imaging showed fairly rich blood signal in 8 tumors,a small amount of blood signal around tumor in 6 tumors and no blood signal in the rest.In early phase,CEUS showed enhancement in all 19 ureteral lesions,including synchronously enhancement in 8 tumors and delayed enhancement in 11 tumors.In peak time,hypoechogenicity compared to the normal renal cortex was shown in 3 tumors,hyperechogenicity in 11 tumors and isoechogenicity in 5 tumors.In late phase,fast wash-out was displayed in 16 tumors,isochronously wash-out in 1 tumor,delayed wash-out in 1 tumor and unclear in 1 tumor.The detection rates of blood supply and clear boundary in ureteral lesions and the diagnostic sensitivity for ureteral cancer were 74% (14/19),16% (3/19),50% (8/16) by conventional ultrasound respectively.The detection rates of blood supply and clear boundary in ureteral lesions and the diagnostic sensitivity for ureteral cancer were 100% (19/19) ,58% (11/19) ,94% (15/16) by CEUS respectively.The change of these performances was statistically significant between conventional ultrasound and CEUS.Conclusions CEUS can improve blood supply,boundary and the diagnostic sensitivity of ureteral lesions.

Objective To evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis with different stenostic degree as a clinical tool to study intraplaque neovascularization.Methods Fifty-eight patients suspected of carotid stenosis with 73 plaques were studied by standard and contrast-enhanced ultrasound.Plaque echogenicity at standard ultrasound were evaluated.Contrast enhancement within the plaques was categorized as 0 - 4 degree and compared to the stenosis degree and the plaque echogenicity.The degree of stenosis was determined by intravenous digital subtraction angiography.Results In the group with stenosis less than 90% ,stenosis degree was not associated with the grade of contrast enhancement (P =0.358),while the grade of enhancement was significantly higher in the group with sever stenosis(＞90%).The grades of enhancement were significantly different between plaques with different echogenicity (P =0.000).Conclusions Contrast-enhanced real-time ultrasound imaging can demonstrate the enhancement of carotid plaques non-invasively,which is helpful for assessing intraplaque neovascularization and provide valuable information for plaque risk stratification

Objective To evaluate the value of quantitative analysis of real-time elastosonography in the differential diagnosis of benign and malignant thyroid nodules. Methods The elastograms of eight-six patients with 98 thyroid nodules were observed. The strain ratio of each lesion and the averages of those of benignancy and malignancy were calculated. With the ROC curve, the critical point of the strain ratio of different lesions was gotten. All the lesions were confirmed with surgery and pathologic examination. Results The average of strain ratio of benign nodules was 2. 18,while that of malignancy was 8. 48. The strain ratio of benign and malignant lesions were of significant difference statistically (P <0.05). According to ROC curve, the critical point of strain ratio between benign and malignant lesions was 3. 3. Conclusions The quantitative analysis of real-time elastosonography is a newly valuable technique of ultrasonography which is helpful in the differential diagnosis of thyroid lesions.

Objective To evaluate the value of contrast-enhanced ultrasound (CEUS) with high mechanical index(MI) in the diagnosis of renal artery stenosis(RAS). Methods Twenty-one patients with RAS including 3 patients after renal transplantation were studied. Ultrasound contrast agent SonoVue was used and MI was set at about 1 when the CEUS was performed. All patients were examined with conventional color Doppler sonography and CEUS. The diagnostic results of ultrasound were compared with those of intravenous digital subtraction angiography ( DSA), CT angiography(CTA) and MR angiography (MRA). Results The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of conventional color Doppler sonography were 85. 7%, 57. 1 % , 80. 0% , 66. 7% and 76. 2%, respectively, those of CEUS were 100%, 66.7%, 88.2%, 100% and 90.5%, respectively. Conclusions CEUS with high MI which improves the imaging of renal artery depicts the margin of the vascular lumen directly and clearly. It may be more helpful in the diagnosis of RAS.

Objective To assess the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of focal liver lesions before microwave ablation. Methods One hundred and seven patients with 128 focal liver lesions underwent CEUS and color Doppler flow imaging (CDFI) before microwave ablation therapy. The diagnostic performance of CEUS and CDFI was compared with pathologic findings through biopsy. Results The sensitivity, specificity, positive and negative predictive value, accuracy of CEUS for diagnosing liver lesions was 98.35% (119/121), 100% (7/7), 100% (119/119), 77.78% (7/9) and 98.44% (126/128), respectively, higher than those of CDFI (P＜0.001). According to CEUS, 119 malignant lesions were treated with timely microwave ablation, while unnecessary microwave ablation was excluded for 7 benign lesions. Conclusion CEUS is useful in the characterization of focal liver tumors before microwave ablation, and is helpful to reduce the misdiagnosis and mistreatment of the patients.