1.Blocking IL-17A protects against lung injury-induced pulmonary fibrosis through promoting the activation of p50NF-kappaB.
Su MI ; Zhe LI ; Hong LIU ; Zhuowei HU ; Fang HUA
Acta Pharmaceutica Sinica 2012;47(6):739-44
This study is to determine the preventive effect and mechanism of targeting IL-17A on pulmonary inflammation and fibrosis after acute lung injury. Mice were treated with anti-IL-17A antibody on the day 7 and sacrificed on the day 14 after bleomycin lung injury. The pulmonary inflammatory status and the deposition of collagen were measured by HE and Sirius stains staining. The contents of hydroxyproline and collagen were measured by using commercial kits. The survival rate of mice was calculated by Kaplan-Meier methods. The inflammatory cytokines in bronchoalveolar lavage fluid were measured by ELISA and the expressions of inflammation-related molecules were detected by Western blotting assay. Targeting of IL-17A could prevent the development of lung inflammation, decrease collagen deposition and the contents of hydroxyproline, and protect against the development of pulmonary fibrosis, which together led to an increase in the animal survival. Moreover, blocking IL-17A decreased the expression ofpro-fibrotic cytokines such as IL-17A, TGF-beta1 and IL-13; increased the expression of anti-fibrotic or anti-inflammatory factors such as IFN-gamma, COX-2, 5-LOX, 15-LOX. Indeed, IL-17A antagonism suppressed the activation of pro-inflammatory p65NF-kappaB but enhanced the activation of pro-resolving p50NF-kappaB. In conclusion, that blockade of IL-17A prevents the development of pulmonary fibrosis from acute lung injury, is because blocking IL-17A may prevent acute inflammation converting to chronic inflammation.
2.Autophagy in ageing and ageing-related diseases.
Fang HUA ; Jiaojiao YU ; Ke LI ; Zhuowei HU
Acta Pharmaceutica Sinica 2014;49(6):764-73
Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
3.Use of posterior or anterior renal lip incision for partial nephrectomy in the treatment of renal hilum endophytic renal cell carcinoma
Zhiling ZHANG ; Yonghong LI ; Pei DONG ; Zhuowei LIU ; Fangjian ZHOU
Chinese Journal of Urology 2015;36(3):172-174
Objective To introduce our experience of performing posterior or anterior renal lip incision for partial nephrectomy in the treatment of renal hilum endophytic renal cell carcinoma.Methods From Jan.2010 to Jan.2014,five female patients with renal hilum tumors were treated in our institute.The median age was 54 (51-72) years.The median tumor diameter was 4.0 (2.8-4.8) cm.The median preoperative creatinine was 53.9 (52.6-75.4) μmol/L.One of them was solitary kidney with absolute indication; three cases had basic disease with relative indication; one was with selective indication.The patients were put in supine or lateral position.After general anesthesia,we preformed partial nephrectomy by cutting posterior renal lip in 3 cases and the anterior lip in 2 cases.We clamped the renal artery,opened the renal posterior or anterior lip,then dissected the tumor beside the pseudo-capsule.After removing the tumor,we used 3-0 absorption suture to control bleeding and repair the opened collecting system.Finally,we used 2-0 absorption suture to close the renal defect.Results The median operation time was 195 (155-215) min; the median renal warm ischemia time was 35 (15-70) min; the median postoperative hospital stay was 8 (7-9) d.There was no secondary bleeding and urine leakage happened.The pathological results showed that 3 cases with clear cell carcinoma,1 with papillary carcinoma and 1 with renal medullary interstitial cell tumor.All patients showed normal kidney shape.The median postoperative creatinine was 63.0 (59.4-75.4) μmol/L.After a median follow up of 24.2 mon,all patients survive without tumor recurrence.Conclusions The short-term result of posterior or anterior renal lip incision partial nephrectomy in treating endophytic renal hilum endophytic renal cell carcinoma is safe and feasible.
4.Establishment and application of TLR2 receptor-based cell screening model.
Ke LI ; Fang HUA ; Xiaoxi Lü ; Jiaojiao YU ; Zhuowei HU
Acta Pharmaceutica Sinica 2013;48(5):694-9
TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.
5.Clinical observation of Shangke Huangshui Gauze on preventing vascular crisis after digital replantation
Haiwen PAN ; Zhaohui WANG ; Zhuowei LI ; Chongzhi ZHAO ; Qingbin LI ; Zhenyu HUANG
Chinese Traditional Patent Medicine 2017;39(5):916-921
AIM To investigate the preventive effects of Shangke Huangshui Gauze (Scutellariae Radix,Coptidis Rhizoma,Phellodendri chinensis Cortex,etc.) on vascular crisis after digital replantation.METHODS Sixty-eight cases of patients with amputated digits meeting the inclusion criteria were randomly divided into observation group (36 cases with 57 fingers) and control group (32 cases with 54 fingers),the former was wet-dressed with Shangke Huangshui Gauze,the latter was bandaged with sterile dry gauze.The observation and comparison were made between the two groups on four coagulation indexes,visual analog scores (VAS),improvement of swelling degrees,the occurrence rates and survival rates of vascular crisis after operation,together with the evaluation of efficacy and adverse reaction.RESULTS In the observation group,the 7th day after operation,the prothrombin time,activated partial thromboplastin time,international normalized ratio,thrombin time and swelling improvement rate were higher than those in the control group;but the fibrinogen and postoperative 4 days' VAS pain score were lower than those in the control group.The incidence rates of vascular crisis and adverse reaction in the observation group were lower than those in the control group,and the survival rate of replanted fingers was higher than that in the control group.CONCLUSION Shangke Huangshui Gauze can prevent the occurrence of vascular crisis after digital replantation to a certain extent without obvious adverse reaction.
6.Clinical research on repairing large area soft tissue defects in heel and crus by flaps with double blood-supply of posterior tibial artery perforators and saphenous nerve nutrient vessels
Haoyu CHEN ; Junqing GAO ; Bin HE ; Jile FU ; Zhuowei LI ; Ying ZENG
Chinese Journal of Microsurgery 2013;(3):225-228
Objective To summarize the curative effect of repairing large area soft tissue defects in heel and crus by flaps with double blood-supply of posterior tibial artery perforators and saphenous nerve nutrient vessels.Methods From January 2006 to February 2012,twenty cases took operation under the guide of Continuous Wave Doppler and design of tibial artery perforator as rotation point.And in all cases,island flaps with the blood supply from saphenous nerve nutrient vessels and tibial artery perforator were retained to repair large area soft tissue defects in heel and crus.In operations,the range of flap area were ranged from 19 cm × 11 cm to 11 cm × 8 cm.Skin flaps incision was up to the patella margin level,low to medial malleolus on edge,former to crus former median line,rear to after crus median line and farthest to the surface of wound on the metatarsophalangeal joint.Results Nineteen cases survived,and 1 case of skin flap mild necrosis at the farthest side took a second-phase line skin flap to repair.Followed-up from 6 months to 24 months was taken in all cases at the mean time of 10 months,with a result of good recovery and no ulceration for the flaps.To varying degree,all flaps recover sense of pain and deep touch.Conclusion There is no wound to posterior main tibial artery in repairing large area soft tissue defects in heel and crus by flaps with double blood-supply from posterior tibial artery perforators and saphenous nerve nutrient vessels,meanwhile to maintain double blood-supply from posterior tibial artery perforators and saphenous nerve nutrient vessels and expand the range of blood supply of posterior tibial artery perforators.In this operation,a blood circulation for the flap can be guaranteed so as for a large wound in heel and crus.
7.Is it essential to excise ipsilateral adrenal in radical nephrectomy?
Zhiling ZHANG ; Zhuowei LIU ; Yonghong LI ; Guoliang HOU ; Hui HAN ; Zike QIN ; Xueqi ZHANG ; Fangjian ZHOU
Chinese Journal of Urology 2010;31(1):35-37
Objective To explore if it is essential to excise ipsilateral adrenal gland in radical nephrectomy.Methods Two hundred and sixty-three patients underwent radical nephrectomy were analyzed retrospectively.The duration of operation,bleeding volumn,complications and survival rates were compared between the adrenalectomy and adrenal preserved groups.The clinical data of the patients with adrenal gland involvement were analyzed as well.Results There were 214 clinical localized(T_(1-2)N_0M_0 )renal cell carcinoma (RCC) patients,26 local advanced RCC(T_(3-4)N_(0-2)M_0 ) patients and 23 metastatic RCC(T_(1-4)N_(0-2)M_1) patients in this study.In the 263 patients,146 cases received ipsilateral adrenal gland excisions,while 117 cases had the ipsilateral adrenal glands preserved.The duration of operation,estimated blood loss and the complications did not differ significantly between these two groups.Only 8 patients had adrenal gland involvement.The mean size of the 8 tumors was 9.7 cm and 5 of them had a diameter ≥8 cm.In the 8 patients,6 had the tumor in the upper pole and 2 had the whole kidney involved.One hundred and twenty-nine clinical stage Ⅰ and Ⅱ patients had ipsilateral adrenal excised,while only 4 (3.1%) had adrenal gland involvement.Seventeen clinical stage Ⅲ and Ⅳ patients had ipsilateral adrenal excised,and 4 (23.5%) had adrenal gland involvements.The clinical stages of these 8 patients were stage Ⅲand Ⅳ.The patients were followed up for 28 months (3-102 months).There was no significant difference of 5-year survival rates between the ipsilateral adrenal gland excised and preserved patients categorized according to pathological stage.Conclusion For patients with renal cancer larger than or equal to 8 cm,localized in upper pole of kidney or with the whole kidney involve and with a clinical stage higher or equal to Ⅲ,it is essential to excise ipsilateral adrenal gland in radical nephrectomy,otherwise the ipsilateral adrenal can be preserved.
8.Feasibility of QOL score in functional assessment of orthotopic neobladder after radical cystectomy
Hui HAN ; Fangjian ZHOU ; Bin WANG ; Yonghong LI ; Zike QIN ; Zhuowei LIU ; Xiaofeng CHEN
Chinese Journal of Urology 2008;29(6):411-414
Objective To estimate the feasibility of QOL score in functional assessment of or-thotopic neobladder after radical cystectomy. Methods Questionnaire survey,QOL score sheet and urodynamic examination were done in 22 patients with orthotopic neobladder.Investigations were fo-CUS on the micturition interval during daytime and nighttime.Micturition time,degree of incontinence and their relationship with QOI.scores and urodynamic parameters wete also analyzed. ResuIts There were 3,6,7,1,2,3 and 0 cases which QOI.score were 0 to 6 accordingly.In the dav time,2 patients complained a light incontinence while 1 patient of moderate incontinence.In the nighttime.3 patients had the complaint of moderate incontinence while 4 patients of light incontinence.The average daytime mlcturltlon interval was 136 min(45-210 rain).The average maximum urinary flow rate,maximal urethral closure pressure and postvoid residual were 12.9 ml/s(2.7-22.1 ml/s),69.3 cm H2O(33-114 em H20)and 91.8 ml(5-300 m1)respectively.QOL scores had D.sitive correlation with the degree of incontinence during daytime and nighttime(daytime:r-0.510,P=0.015,night time:r=0.911,P<0.001).The QOL scores had negative correlation with daytime micturition inter-val(r=-0.749,P<0.001).The factors which influenced the QOL scores included the maximaI ure-thral closure pressure,postvoid residual and the maximum urinary flow rate. Conclusions QOL score reflects the patients"continent ability,subjective feelings on quality of life.It is correlated with the common urodynamic parameters.QOI.score might be used as a new index to estimate the function of orthotopic neobladder.
9.Modified technique of radical inguinal lymphadenectomy to reduce the complication of skin necrosis for penile carcinoma
Hui HAN ; Kai YAO ; Zijun ZOU ; Yonghong LI ; Zike QIN ; Zhuowei LIU ; Fangjian ZHOU
Chinese Journal of Urology 2011;32(12):811-814
Objective To report a modified radical inguinal lymphadenectomy the aim of which is to reduce the incidence of the complication of skin necrosis.Methods One hundred and twenty-six modified radical inguinal dissections were performed in 63 patients with penile carcinoma from June 2002 to June 2010.A modified radical inguinal dissection characterized by an S-shaped incision and precisely separating layers using an anatomical mark was performed.The boundaries of dissection were the same as classic radical inguinal lymphadenectomy.The incidences of complications of skin flap necrosis were retrospectively analyzed.Results The follow-up time ranged from 12 to 93 months.A total of 37 complications occurred,including 7 minimal skin necroses (5.6%),3 wound infections (2.4%),19 lymphedemas (15.1%),2 seroma formations (1.6%),5 lymphocele (4.0%),and 1 deep venous thrombosis (0.8%).There were no complications in 106 dissections (84.1% ),and 20 dissections had one or two minor complications ( 15.9% ).Conclusions The complication of skin necrosis related to groin dissection in patients with penile carcinoma could be reduced by using this modified inguinal dissection technique,which characterized by an S-shaped incision and precisely separating layers with using an anatomical landmark.
10.Laparoscopic nephroureterectomy for local renal pelvic carcinoma with poorly differentiated tumor:comparison with open nephroureterectomy
Zhuowei LIU ; Fangjian ZHOU ; Cuoliang HOU ; Hui HAN ; Zike QIN ; Shaolong YU ; Yonghong LI ; Kai YAO ; Harabayashi TORU
Chinese Journal of Urology 2008;29(z1):19-21
Objective To evaluate the efficacy and application value of retroperitoneal laparoscopic nephroureterectomy for localized and poor differentiated renal pelvic carcinoma by comparing with open nephroureterectomy.Methods Thirty-three pelvic carcinoma patients underwent radical nephroureterectomy were retrospeetively analyzed.All tumors were confirmed to be localized,stage T1-T3 and grade 3.Retroperitoneal laparoscopic nephroureterectomy was performed in 12 patients,the ureteral orifice was resected in traditional way through a small incision in lower abdomen.Open radical nephroureterectomy was performed in 21 cases.Clinical outcomes of the patients were compared between the 2 surgery groups.Results Mean operative time was 232 vs 212 min(P=0.100)and blood loss volume was 162 vs 233 ml(P=0.001)in the laparoscopic and open nephroureterectomy groups.Mean postoperative hospitalization was 7.6 vs 9.8 d(P<0.001)for the laparoscopic and open groups.During the followup for 7-67 months,all the 33 patients survived.There was no recurrence or metastasis in laparoscopic group.While there was 1 retroperitoneal recurrence,and 3 cases suffering from superficial bladder cancer in open surgery group.Conclnsion Retroperitoneal laparoscopic nephroureterectomy may be performed safely in local renal pelvic carcinoma patients with poor differentiated tumors,with less intraoperative blood loss and early recovery.