WNT1-inducible signaling protein-1 mediates TGF-β1-induced renal fibrosis in tubular epithelial cells and unilateral ureteral obstruction mouse models via autophagy

Renal fibrosis is a common pathway for the progression of all chronic kidney diseases to end-stage kidney disease. Studies show that WNT1-inducible signaling pathway protein-1 (WISP-1) is involved in the fibrosis of various organs. The aim of the study was to explore the functional role and potential mechanism of WISP-1 in renal fibrosis. We observed that overexpression of WISP-1 in rat tubular epithelial cells (TECs) enhanced transforming growth factor-β1 (TGF-β1)-induced production of fibrotic markers, including collagen I (Col I), fibronectin (FN) and TGF-β1, while inhibition of WISP-1 suppressed such production. In vivo, the messenger RNA and protein levels of Col I, FN, and α-smooth muscle actin were significantly inhibited after anti-WISP-1 antibody treatment for 7 days in unilateral ureteral obstruction mouse models. Moreover, blockade of WISP-1 by anti-WISP-1 antibody significantly reduced autophagy-related markers, including anti-microtubule-associated protein-1 light chain 3 (LC3) and beclin 1, while increasing sequestosome 1. In addition, overexpression of WISP-1 in TECs increased autophagy as evidenced by greater numbers of GFP-LC3 puncta and increased expression of LC3 and beclin 1 in response to TGF-β1. In contrast, knockdown of WISP-1 by small interfering RNA decreased the number of GFP-LC3 puncta and the expression of LC3 and beclin 1 in TGF-β1-treated TECs. Collectively, these data suggest that WISP-1, as a profibrotic protein, may mediate renal fibrosis by inducing autophagy in both obstructive nephropathy and TGF-β1-treated TECs. WISP-1 may serve as an effective therapeutic target for the treatment of renal fibrosis.     

超声引导下肝内胆管置管治疗肝内胆管结石并发梗阻的临床效果观察

目的:探究超声引导下肝内胆管置管治疗肝内胆管结石并发梗阻的临床效果和安全性。方法:选择2014年1月至2018年1月于我院接受治疗的98例肝内胆管结石并发梗阻患者为研究对象,将患者按照入院顺序统一编号后,根据随机数字表法进行分为实验组与对照组,每组各49例患者。对照组患者于常规X线引导下行肝内胆管置管治疗,实验组患者在超声引导下实施肝内胆管置管治疗,对比两组患者穿刺次数、手术时间、术后并发症的发生情况,并对两组患者随访3个月,比较其结石残余率及治疗效果。结果:(1)实验组患者穿刺次数及操作时间均显著少于对照组(P0.05);(2)实验组患者术后各类并发症发生率为4.08%,明显低于对照组(20.41%,P0.05);(3)对照组患者后3个月的结石残余率为14.29%(7/49),实验组为2.04%(1/49),显著低于对照组(P0.05);(4)术后3个月,实验组患者治疗总有效率为97.96%,明显高于对照组(81.63%,P0.05)。结论:与常规X线引导下行肝内胆管置管治疗相比,超声引导下肝内胆管置管在治疗肝内胆管结石并发梗阻中具有较更好的治疗效果和安全性。     

奥曲肽治疗急性粘连性肠梗阻疗效观察

目的:探讨生长抑素对腹部手术后急性粘连性肠梗阻的治疗作用。方法:70例急性粘连性肠梗阻患者随机分为观察组与对照组各35例。对照组予胃肠减压、灌肠、补液及抗感染治疗等常规治疗;观察组在此基础上加用奥曲肽(生长抑素类似物)0.1 mg皮下注射,每8h一次,治疗72 h。观察两组患者腹痛评分、腹痛缓解时间、胃肠减压量、肛门恢复排气时间、立卧位腹部平片、临床缓解情况。结果:观察组34例(97.1%)临床缓解,明显高于对照组的28例(80.0%)(P<0.05)。与对照组相比,观察组在治疗第1、2天后腹痛评分明显下降(均为P<0.01),腹痛缓解时间显著缩短(P<0.01),治疗第1、2、3天的胃肠减压量均显著减少(均为P<0.01),恢复排气时间也明显缩短(P<0.01)。结论:急性粘连性肠梗阻在常规治疗基础上加用生长抑素,可明显改善临床症状,提高疗效。     

肾包膜下积液的临床分析(附23 例报告)

目的:探讨肾包膜下积液的成因和治疗方法。方法:回顾分析23例肾包膜下积液的临床资料。结果:本组23例中,除1例因肿瘤致尿路梗阻放弃治疗,余均经治疗后肾包膜下积液治愈。结论:肾包膜下积液病因以梗阻性为多见,解除梗阻后可治愈;原因不明的特发性肾包膜下积液,肾包膜下穿刺引流术因创伤小,是首选方法,对穿刺引流术治疗后复发病例,可选择手术治疗。     

Prediction of stenting related adverse events through patient-specific finite element modelling

Right ventricular outflow tract (RVOT) calcific obstruction is frequent after homograft conduit implantation to treat congenital heart disease. Stenting and percutaneous pulmonary valve implantation (PPVI) can relieve the obstruction and prolong the conduit lifespan, but require accurate pre-procedural evaluation to minimize the risk of coronary artery (CA) compression, stent fracture, conduit injury or arterial distortion.Herein, we test patient-specific finite element (FE) modeling as a tool to assess stenting feasibility and investigate clinically relevant risks associated to the percutaneous intervention.Three patients undergoing attempted PPVI due to calcific RVOT conduit failure were enrolled; the calcific RVOT, the aortic root and the proximal CA were segmented on CT scans for each patient. We numerically reproduced RVOT balloon angioplasty to test procedure feasibility and the subsequent RVOT pre-stenting expanding the stent through a balloon-in-balloon delivery system.Our FE framework predicted the occurrence of CA compression in the patient excluded from the real procedure. In the two patients undergoing RVOT stenting, numerical results were consistent with intraprocedural in-vivo fluoroscopic evidences. Furthermore, it quantified the stresses on the stent and on the relevant native structures, highlighting their marked dependence on the extent, shape and location of the calcific deposits. Stent deployment induced displacement and mechanical loading of the calcific deposits, also impacting on the adjacent anatomical structures.This novel workflow has the potential to tackle the analysis of complex RVOT clinical scenarios, pinpointing the procedure impact on the dysfunctional anatomy and elucidating potential periprocedural complications.     

Foreign body urethral obstruction in a chimpanzee (Pan troglodytes)

Background  A 34-year-old, captive-born, vasectomized male chimpanzee ( Pan troglodytes ) presented with lethargy and scrotal swelling.
Methods  Urethral obstruction was diagnosed via urethroscopy.
Results  Removal of the grass stem foreign body resolved the obstruction. Scrotal and preputial ulceration developed from urine scald, which was managed with surgical debridement and antibiotics.
Conclusions  After 7 weeks, the animal was reintroduced to its troup and has been healthy for 11 months.     

骨性Ⅲ类错合畸形患者正颌术后呼吸道情况随访调查

目的：通过评估骨性Ⅲ错合畸形患者正颌手术后睡眠时期的呼吸功能情况,研究该类患者正颌手术后存在呼吸道梗阻的可能性。为临床治疗提供依据。方法：分析56例接受正颌手术的骨性Ⅲ类错合畸形患者的术前及术后1周、1月、3月和术后6月的多导睡眠图报告。设计问卷调查表评估手术影响日间嗜睡度的变化。从PSG报告上获得的术前术后有代表性的2项参数睡眠呼吸暂停低通气指数与最低氧饱和度分别进行比较。结果：数据显示术前和术后AHI指数及SpO2无显著性差异（统计学上无差异）。54例病人术后均未出现睡眠呼吸障碍症状。2例病人术后出现睡眠时期打鼾,但术后随访6月后打鼾逐渐消失。结论：骨性Ⅲ类错合畸形患者正颌术后无明显呼吸道梗阻症状。但若患者同时具有超重、短颈、舌体大等其他危险因素及仅行下颌骨后退手术可能导致睡眠呼吸暂停低通气综合症的发生。     

Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells

Cell stress may give rise to insuperable growth arrest, which is defined as cellular senescence. Stenotic kidney (STK) ischemia and injury induced by renal artery stenosis (RAS) may be associated with cellular senescence. Mesenchymal stem cells (MSCs) decrease some forms of STK injury, but their ability to reverse senescence in RAS remains unknown. We hypothesized that RAS evokes STK senescence, which would be ameliorated by MSCs. Mice were studied after 4 weeks of RAS, RAS treated with adipose tissue‐derived MSCs 2 weeks earlier, or sham. STK senescence‐associated β‐galactosidase (SA‐β‐Gal) activity was measured. Protein and gene expression was used to assess senescence and the senescence‐associated secretory phenotype (SASP), and staining for renal fibrosis, inflammation, and capillary density. In addition, senescence was assessed as p16+ and p21+ urinary exosomes in patients with renovascular hypertension (RVH) without or 3 months after autologous adipose tissue‐derived MSC delivery, and in healthy volunteers (HV). In RAS mice, STK SA‐β‐Gal activity increased, and senescence and SASP marker expression was markedly elevated. MSCs improved renal function, fibrosis, inflammation, and capillary density, and attenuated SA‐β‐Gal activity, but most senescence and SASP levels remained unchanged. Congruently, in human RVH, p21+ urinary exosomes were elevated compared to HV, and only slightly improved by MSC, whereas p16+ exosomes remained unchanged. Therefore, RAS triggers renal senescence in both mice and human subjects. MSCs decrease renal injury, but only partly mitigate renal senescence. These observations support exploration of targeted senolytic therapy in RAS.     

METTL3/N6-methyladenosine/ miR-21-5p promotes obstructive renal fibrosis by regulating inflammation through SPRY1/ERK/NF-κB pathway activation

Renal fibrosis induced by urinary tract obstruction is a common clinical occurrence; however, effective treatment is lacking, and a deeper understanding of the mechanism of renal fibrosis is needed. Previous studies have revealed that miR-21 impacts liver and lung fibrosis progression by activating the SPRY1/ERK/NF-kB signalling pathway. However, whether miR-21 mediates obstructive renal fibrosis through the same signalling pathway has not been determined. Additionally, studies have shown that N6-methyladenosine (m⁶A) modification-dependent primary microRNA (pri-microRNA) processing is essential for maturation of microRNAs, but its role in the maturation of miR-21 in obstructive renal fibrosis has not yet been investigated in detail. To address these issues, we employed a mouse model of unilateral ureteral obstruction (UUO) in which the left ureters were ligated for 3, 7 and 14 days to simulate the fibrotic process. In vitro, human renal proximal tubular epithelial (HK-2) cells were transfected with plasmids containing the corresponding sequence of METTL3, miR-21-5p mimic or miR-21-5p inhibitor. We found that the levels of miR-21-5p and m⁶A modification in the UUO model groups increased significantly, and as predicted, the SPRY1/ERK/NF-kB pathway was activated by miR-21-5p, confirming that miR-21-5p plays an important role in obstructive renal fibrosis by enhancing inflammation. METTL3 was found to play a major catalytic role in m⁶A modification in UUO mice and drove obstructive renal fibrosis development by promoting miR-21-5p maturation. Our research is the first to demonstrate the role of the METTL3-m⁶A-miR-21-5p-SPRY1/ERK/NF-kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis.     

多层螺旋CT检查与腹部X线平片对急性肠梗阻的诊断价值比较研究

目的:研究比较多层螺旋CT(MSCT)检查与腹部X线平片对急性肠梗阻(AIO)的诊断价值。方法:选择2016年1月到2018年4月间在蚌埠医学院附属阜阳医院接受手术治疗的200例AIO患者作为研究对象,对所有患者先常规予以腹部X线平片诊断,12h后再通过MSCT为患者实施诊断,对比两种方法的诊断结果、诊断体验效果以及漏诊率和误诊率。结果:MSCT的肠梗阻检出率为94.50%,明显较腹部X线平片的69.00%更高(P0.05)。MSCT所诊断的肠梗阻中,梗阻类型为绞窄型及梗阻病因为肠肿瘤者均占100.00%,较腹部X线平片的36.21%和54.26%明显更高(P0.05)。MSCT的诊断舒适度评分、图像清晰度评分较腹部X线平片明显更高,而操作复杂度评分较腹部X线平片明显更低(P0.05)。MSCT的漏诊率、误诊率分别为4.00%、1.50%,较腹部X线平片的22.00%、9.00%明显降低(P0.05)。结论:对于AIO患者,MSCT较腹部X线平片具有更高的诊断价值,诊断体验效果更好,漏诊率和误诊率偏低。