Aim To investigate the effects of Ang Ⅱ receptor antagonist irbesartan on the expressions of connective tissue growth factor(CTGF) and membrane-type 1 matrix metalloproteinase(MT1-MMP) in high glucose-cultured rat glomerular mesangial cells(GMCs).Methods High concentration glucose and irbesartan were used to stimulate the cultured rat GMCs in vitro.The mRNA and protein expressions of CTGF and MT1-MMP were detected with semi-quantitative RT-PCR and Western blot.The secreted collagen Ⅳ in the supernatants of the GMCs was detected by enzyme-linked immunoadsorbent assay(ELISA).Results Compared with control group,the expressions of CTGF were continuously increased in GMCs under high concentration glucose medium;otherwise the mRNA and protein levels of MT1-MMP in GMCs were decreased in a time-dependent manner at the same time.These changes were accompanied by increased secretion of collagen Ⅳ.Irbesartan could inhibit those changes induced by high glucose.Conclusions High glucosecould induce the expression of CTGF and inhibit the expression of MT1-MMP in GMCs.Irbesartan could inhibit the secretion of ECM in GMCs under high concentration glucose medium,partly by regulating the expressions of CTGF and MT1-MMP.

Recent years, China has released a series of policies to encourage drug research and development in pediatric populations, aiming to meet pediatric populations' medical needs. Because of the physical and psychological developmental characteristics, tolerance of aversive feelings when taking medications are different between pediatric population and adults. So pediatric populations are at a relatively higher risk of not taking medications as prescribed when the medication tasted unpleasant. Therefore, sound design and evaluation of oral sensory features have important clinical significance and value in developing pediatric medications. "Technical guidance for the design and evaluation of the oral sensory features of pediatric drugs (trial version) " was released in November 2022, by Centre for Drug Evaluation, National Medical Products Administration of China. Based on the guidance, this article will introduce the drafting background and review considerations, hoping to provide reference for the design and evaluation of oral sensory features, and promote drug developing in pediatric population.

Objective To investigate the significance of neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the patients of primary nephmpathy syndrome (PNS) complicated with acute kidney injury (AKI) by detecting urinary level of NGAL and KIM-1.Methods Senventy-two patients of PNS were selected as our subjects including 34 case with minimal change disease (MCD),23 cases with membranous nephropathy(MN),15 cases with mesangial proliferative glomerulonephritis (MsPGN).Fifteen cases of healthy physical examination were selected as control group.Meanwhile subjects were also divided into PNS with ATN group (15 cases) and PNS without ATN group (57 cases) according to their pathology check.ELISA was applied to detect the urinary level of NGAL and KIM-1,whose correlation with pathological type and clinical index were analyzed.Results The urinary level of NGAL and KIM-1 in patients with PNS were (42.37 ± 28.24) μg/L,(2.76 ± 1.11) μg/L respectively,higher than that of control group (P ＜0.01).The urinary level of NGAL in the MCD group,MN group,MsPGN group were higher than that of control group (46.81 ± 15.75) μg/L,(22.09 ± 7.69) μg/L,(15.31 ± 3.74) μg/L,(8.03 ± 0.35) μg/L respectively,P ＜ 0.05).The urinary level of NGAL in MCD group was significantly highest than that in the other groups (P ＜ 0.05).The urinary level of KIM-1 in the MCD group,MN group,MsPGN group were higher than that of control group(2.41 ±0.58) μg/L,(2.54 ±0.67) μg/L,(2.87 ±0.50) μg/L,(0.73 ±0.35) μg/L respectively,P ＜0.05).But there was no significant difference among MCD,MN,MsPGN groups(P ＞ 0.05).The urinary level of NGAL and KIM-1 in patients PNS were (42.37 ± 28.34) μg/L and (2.76 ± 1.11) μg/L,significantly higher than that of control group (t =4.668,12.665,P ＜ 0.05).The urinary level of NGAL and KIM-1 in patients PNS with ATN were significantly higher than patient without ATN (NGAL:(74.98 ±9.52) μg/L vs.(31.31 ±2.34) μg/L;KIM-1:(3.60 ±0.92) μg/L vs.(2.54 ±0.81) μg/L,P ＜0.05).The correlation analysis showed that the urinary level of NGAL and KIM-1 was positively correlated with serum β2-MG,serum creatinine,serum blood urea nitrogen and 24-hour urine protein.(r =0.432,0.299,0.234,0.254,0.434,0.650,0.276,0.301 respectively,P ＜ 0.05).Conclusion The urinary level of NGAL and KIM-1 could be considered as the early,non-invasive biologic factors to reflect in patients of PNS with ATN.

The chemical components of mainstream smoke were trapped by the artifical salvia. A novel method) for the analysis of the trapped chemical components was established using stir bar sorptive extraction(SBSE)) followed by a thermal desorption-gas chromatography-mass spectrometry(TD-GC-MS). The major) factors including desorption temperature, desorption time, cryofocusing temperature, extraction time and the addition of sodium chloride were studied. Under the optimized conditions, the average relative standard deviation(RSD) of peak areas of 44 components which were identified from the artifical saliva for 6 determinations was less than 10%, which showed the good repeatability of this method. The experiment result indicated that the SBSE-TD-GC-MS technique provided a powerful tool for the analysis of smoke components of some cigarette) trapped and dissolved in the saliva.

Objective To report our surgical experience in treating 19 cases of solitary iliac aneurysms (SIA). Methods The clinical data of 19 consecutive patients with SIA between January 1985 and January 2008 were retrospectively reviewed. There were 18 men and 1 woman, aging from 39 to 77 years ( mean 62 ± 7 years). Results There were 30 SIAs in the 19 patients, including 25 ( 83.3% ) common iliac aneurysms, 4 (13.3%) internal ihac aneurysms and 1 (3. 3% ) external iliac aneurysm. Eleven patients ( 57.9% ) had multiple ancurysms, with 9 patients ( 47.4% ) having bilateral SIA. Two patients had coexistent peripheral vascular occlusive disease. There were 2 patients suffering form ruptured SIA, one was saved by emergency operation and one died before an surgery could be attempted. Seventeen patients underwent successful open aneurysmectomy and artificial graft implantation leaving no ischemic complications of the pelvic organs. One patient with right common iliac aneurysm underwent endovascular repair without endoleak. There was no operative death during porioperative period. The surviving patients remained stable and had good patency of grafts during the follow-up period. Conclusions Early management of SIA is important, CT angiogarphy (CTA) is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term follow-up is mandatory for the early detection of the formation of new anearysms.

Objective To summarize and analyze the surgical therapies for liver and gastric multiple primary cancers. Methods The clinical data of 14 patients with liver and gastric carcinomas surgically treated in our hospital from January 2004 to January 2008 were retrospectively analyzed.Results Of the 14 patients, 12 underwent simultaneous resection of liver and gastric carcinomas,1 resection of the gastric carcinoma 2 months after the liver surgery and 1 removal of liver cancer found 2 years after the surgery for antral adenocarcinoma. The median survival time of these patients was 23 months. The 1-and 3-year survival rate was 78.6% and 35.7%, respectively. Conclusion Due to different pathological characteristics, the therapies of liver and gastric multiple primary cancers are completely different from that of the recurring and metastatic carcinoma. Both tumors can be treated by radical resection and the effect is similar to single cancer. Positive treatment is crucial for long-term survival of the patients.

Objective To evaluate the safety and efficacy of induction chemotherapy with gemcitabine followed by concurrent chemoradiotherapywith capecitabine in patients with locally advanced pancreatic cancer (LAPC).Methods A total of 42 patients with locally advanced pancreatic cancer were enrolled.All patients received seven cycles of induction chemotherapy of gemcitabine 1 000 mg/m2,once a week.Concurrent chemoradiotherapy began 1 week after completion of induction chemotherapy.Radiotherapy was delivered with a median dose of 54 Gy (34-64 Gy) with 1.8-2.0 Gy in a fraction.The radiotherapy was combined with capecitabin at a dosage of 825 mg/m2 twice daily,5 d/week.Results Twenty patients (47.6％) were evaluated as clinical benefit response (CBR).Two cases were observed with complete remission (CR),8 with partial remission (PR),27 with stable disease (SD),and 5 with progressive disease (PD).The median overall survival was 10.1 months (range of 4-36 months).The 1-,2-year overall survival rate was 38.2％ and 18.2％,respectively.Myelosuppression was recorded in 20 patients with grades 1-2,and 5 patients with grade 3.Twenty-two patients suffered from grade 1-2 gastrointestinal toxicities,while 4 patients suffered from grade 3.Conclusions The preliminary results showed that induction chemotherapy with gemcitabine followed by concurrent chemoradiotherapy with capecitabine in patients with LAPC might achieve encouraging efficacy with better tolerance.

Objective To investigate the diagnosis and treatment methods of traumatic renal infarction.Methods A retrospective analysis was performed on 6 cases of traumatic renal infarction treated between September 2008 and February 2013.There were 5 males and 1 female,at age of 5-65 years (average,36.2 years).Causes of injury included vehicle collisions in 4 cases and high falls in 2.Out of 6 cases,segmental renal infarction was identified in 2 and total infarction in 4.According to American Association for the surgery of trauma renal trauma grading system,2 cases were classified to grade Ⅳ and 4 to grade Ⅴ.Results Three cases were managed conservatively,which showed segmental infarction in 1 case and total infarction in 2.Three cases underwent surgical exploration,followed by partial nephrectomy in 1 case,left kidney removal plus partial pancreectomy in 1 and right kidney removal in 1.There were no major complications intraoperatively or postoperatively and no cases received blood transfusion.Period of follow-up was 3-34 months.In conservative management,there were no renal atrophies in segmental renal infarction cases and some degree of atrophies in total renal infarction cases,but none presented with arterial hypertension.Conclusions Enhanced CT is the preferred diagnostic tool for evaluation of traumatic renal infarction.Conservative therapy is the optimal option for most cases,but nephrectomy is reserved for cases of infection or renal hypertension.

Objective To study intermediate and long term efficacy of uterine arterial embolization (UAE)with sodium alginate microspheres(KMG)at diameters 500-700μm in treatment of diffuse adenomyosis.Methods Totally 40 patients with standard difluse adenomyosis were enrolled and treated with UAE.KMG at diameters 500-700 μm for vascular embolization were used to embolize the arteries.The degree of dysmenorrhea,amount of menorrhea and uterine volume,as well as the level of serum CA125,follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2)were investigated before andafter UAE.Results The follow up rates were 100%(40/40),100%(40/40),80%(32/40),68%(27/40),58%(23/40)after uterine arterial UAE 12,24,36,48 and 60 months respectively.The early,intermediate and long-term effective rates were 90%(36/40),88%(28/32),83%(19/23).The degree of dysmenorrhea,the amount of menorrhea and the uterine volume,as well as serum CA125 all decreased significantly 3 mouths after UAE at varying degrees(P＜0.05).Compared with other follow-up time,thedegree of dysmenorrhea and the amount of menorrhea declined to their lowest point at 6 month after UAE (P＜0.01).Paralleled with the decrease of volume of uterine,serum CA125 also decreased significantly and reached the lowest level 12 months later compared with other follow-up times(P＜0.01).Even at the 12th month after UAE serum CA125was not normal and FSH,LH and E2 did not change all the times after UAE(P>0.05).No recurrence was found during the 60 months after UAE.Condusion KMG used in UAE at diameters 500-700 μm has good intermediate and long term effectiveness in treatment of diffuse adenomyosis with no side effects.

Aim To investigate the effects of irbesartan on Wnt/β-catenin signaling pathway in tubular epithelial-mesenchymal transition(EMT)in HKCs induced by high-glucose.Methods Human kidney proximal tubular epithelial cell line(HKCs)cultured in vitro was divided into four groups:normal-glucose group,mannitol control group,high-glucose group and high-glucose plus irbesartan group.Immunocytochemistry staining was used to observe the expression of β-catenin;the protein expression of Wnt4,β-catenin,E-cadherin and α-SMA was assessed by Western blot;Wnt4 and β-catenin mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with normal-glucose and mannitol control group,both the protein and the mRNA of Wnt4 were up-regulated in HKCs stimulated by high-glucose.α-SMA expression significantly increased but E-cadherin decreased in HG group.The cytoplastic and nuclear fraction of β-catenin enhanced with highglucose stimulation.But no difference of the total protein and mRNA of β-catenin was observed between highglucose-treatment and control groups.Highglucose induced Wnt4 and β-catenin expression in a time-dependent manner,both peaking at 24 h.Irbesartan reduced the promotional effect of HG on Wnt4 and α-SMA expression,and nuclear translocation of β-catenin.HG-mediated inhibition of E-cadherin was also restored by irbesartan.Conclusion These data supported a functional role for Wnt/β-catenin signaling pathway during epithelial-mesenchymal transition of HKCs induced by high glucose and suggested that irbesartan might reverse tubular EMT by regulating activity of Wnt/β-catenin pathway.