Candesartan early or late treatment reduced advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mice kidney / 中国医师杂志

Objective The effects of candesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) were investigated on advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mouse kidneys.MethodsKK/Ta mice(n=72)were random divided into three groups(n=24) and it was treated with candesartan [4 mg/(kg·d)] or vehicle from 6 or 12 to 28 weeks of age.BALB/c mice(n=24) treated with vehicle were used as controls.Body weight,blood pressure,blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks,renal expressions of carboxymethyllysine and RAGE were evaluated by immunohistochemistry and/or competitive RT-PCR.Results KK/Ta mice developed high body weight,high blood glucose,and high urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age,and it was significantly higher than that of BALB/c mice [(427.49±89.37)mg/g vs (9.54±3.25)mg/g,P＜0.01 ].Protein and mRNA expressions of RAGE were upregulated in KK/Ta kidneys with increased immunostaining intensities of carboxymethyllysine.Candesartan treatment has markedly reduced urinary microalbumin/creatinine ratio [Early treatment group (32.18±9.41)mg/g,Late treatment group (53.20±7.26)mg/g,P＜0.01 ].Treatment with candesartan down-regulated the protein and mRNA expressions of RAGE and reduced the accumulation of carboxymethyllysine.There were no significant differences between the two treatment groups (from 6 or 12 weeks).ConclusionsThe results suggest that candesartan,an ARB,reduces advanced glycation end-products accumulation and subsequent albuminuria by down-regulating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.

Syndecan-4 is a candidate gene for diabetic nephropathy / 中华肾脏病杂志

Objective To identify the candidate genes in the vicinity of a susceptibility locus (urinary albumin 1,UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice. Methods Total RNA was extracted from the kidneys of KK/Ta (n=3) and BALB/c (n=2) mice at 20 weeks of age.The gene expression profile in kidney was investigated using the Affymetrix Murine Genome U74Av2 array.Competitive RT-PCR was used to confirm the differential expression of syndecan-4 which located in the vicinity of UA-1.Genome DNA was extracted from KK/Ta and BALB/c mice.DNA sequence analysis of the coding and promotor region of syndecan-4 gene was conducted. Results In the vicinity of the susceptibility locus (UA-1)contributing to the development of albuminuria in type 2 diabetic KK/Ta mice,10 candidate genes that showed differential expression were identified.Among them,the gene expression of syndecan-4in KK/Ta kidneys at 20 weeks of age was up-regulated by 26.1 times of age-matched BALB/c kidneys.Sequence analysis revealed two synonymous polymorphisms in the coding region (A93C and T216C) and three polymorphisms in the promoter region (-T263C,-T396C and -G669A) of the syndecan-4 gene.The TATA box was found at 321 bp upstream from the transcription start site,and the T263C polymorphism was located in the binding site of transcription factor Clox.Conclusions Syndecan-4 gene is mapped in the vicinity of the susceptibility locus contributing to the development of albuminuria in type 2 diabetes.The gene expression of syndecan-4 in KK/Ta kidneys is up-regulated than that in age-matched BALB/c kidneys at 20 weeks of age.Thus syndecan-4 may be one of the potential candidate genes responsible for diabetic nephropathy.Sequence differences in the promoter region influence the expression levels of syndecan-4 genes in KK/Ta kidneys.

Mesenchymal stem cells implantation increases the myofibroblasts congregating in infarct region in a rat model of myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI).</p><p><b>METHODS</b>MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-β(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot.</p><p><b>RESULTS</b>(1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-β(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05).</p><p><b>CONCLUSIONS</b>MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-β(1)-Smad2 signaling pathway in this model.</p>

Treatment of advanced non-small cell lung cancer with extracorporeal high frequency thermotherapy combined with Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and benefit response of extracorporeal high frequency thermotherapy (EHFT) combined with Chinese medicine (CM) in the treatment of patients with advanced nonsmall cell lung cancer.</p><p><b>METHODS</b>The study adopted a prospective, small sample and randomized controlled method, and the advanced non-small cell lung cancer patients were assigned to two groups according to the table of random digits, one having the treatment of EHFT combined with CM (the treatment group), the other only with CM (the control group). The patients in the treatment group were treated with EHFT one hour once per day, together with CM differentiation decoction, 250 mL orally taken, twice daily for 14 days as one cycle, and 3-4 cycles was performed. The patients in the control group were treated only with CM differentiation decoction using the same dose as the treatment group. The efficacies were evaluated after three to four cycles of treatment. Primary endpoints were disease control rate (DCR) and time to progression (TTP). Secondary endpoints were overall survival time and 1-year survival rate.</p><p><b>RESULTS</b>Sixty-six patients accomplished the study. After the patients underwent different treatments, none of the patients got a complete response or partial response in both groups. In the treatment group, DCR was 72.2%, and 10 had progression of disease (28.8%), while the DCR of the control group was 63.3%, and 11 had progression of disease (36.7%); there was a significant statistical difference (P <0.05), suggesting that the combined regimen had superiority on the DCR. As for long-term efficacy, the median survival time (MST) of the treatment group was 7.5 months, TTP was 5.5 months, and 1-year survival rate was 21.4 %; in the control group, the results were 6.8 months, 4.5 months and 16.6% respectively. There was significant statistical difference on TTP (P <0.05), but no difference on MST or 1-year survival rate.</p><p><b>CONCLUSION</b>EHFT combined with CM differentiation has better tolerance and short-term efficacy in the treatment of patients with advanced NSCLC.</p>

Study on Mental Characteristics of Children's with Light Lead Poisoning / 实用儿科临床杂志

Objective To study mental characteristics of children with light lead poisoning. Methods Eighty - six children with light lead poisioning and 33 control children were evaluated with WISC - R and social adaptive capacity(SAB). Results 1. Intelligence quotient( IQ)and SAB of children with light lead poisoning were lower than normal children. 2. There was also deficiency of perception factor and memory/ concentration factor among children with lead poisioning and the blood lead level had negative association with perception factor. Conclusion Light lead poisioning may affect children's IQ, especially in the perception factor and memory /concentration factor.

Mandibular fracture fixed with PDLLA/nano-HA compound plates: an animal study / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the applicability of PDLLA/nano-HA compound plates used in internal fixation of mandibular fractures.</p><p><b>METHODS</b>Rabbit mandibular fracture model was used in this study. Clinical observation, the amount of callus, histological observation were studied and compared with PDLLA plates.</p><p><b>RESULTS</b>All fractures were fixed rigidly. There was 1 animal experienced local inflammation and then forming fistula in the side of PDLLA plate at postoperative 2 and 3 weeks. No side-effects were found in the side of compound plates. During the early stage of bone healing, the quality of callus in the side of compound plates was apparently more than that in the other side, and histological study showed that the osteoblasts and fibroblasts were more active in the side of compound plate in the early healing stage.</p><p><b>CONCLUSIONS</b>PDLLA/nano-HA compound plate has a proper degradation time. Compared with PDLLA plates, it is more effective and safer when used in mandibular fracture.</p>