Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.</p><p><b>METHODS</b>It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.</p><p><b>RESULTS</b>The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.</p><p><b>CONCLUSIONS</b>Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.</p><p><b>TRIAL REGISTRATION</b>chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.</p>

Mycophenolate mofetil affects monocyte Toll-like receptor 4 signaling during mouse renal ischemia/reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mycophenolate mofetil (MMF) has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure. The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 (TLR4) signaling in the early stages of renal ischemia/reperfusion injury (IRI) of mice.</p><p><b>METHODS</b>Sixty BALB/C mice were randomly divided into two groups: an IRI group, in which renal IRI was induced by clamping the renal pedicles for 45 minutes, and an MMF group, in which MMF was given (40 mg×kg(-1)×d(-1), intraperitoneally) from 2 days before renal IRI. The plasma creatinine level and renal tissue damage of each group mice were observed 6, 12, 24, and 48 hours after reperfusion. The concentration of plasma high-mobility group box 1 (HMGB-1) (TLR4 ligand), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) and the expression of TLR-4 on monocytes were determined.</p><p><b>RESULTS</b>The plasma creatinine concentration in the MMF group was lower compared to the IRI group (after reperfusion of 6, 12, 24, or 48 hours, P < 0.05). Pathological analysis showed that the renal damage was slighter, TLR-4 expression was reduced (after reperfusion of 6, 12, 24, or 48 hours, P < 0.05), and the concentration of cytokines in the plasma was lower (P < 0.05) in the MMF group. No differences in the concentrations of HMGB-1 were observed (P > 0.05).</p><p><b>CONCLUSION</b>Monocyte TLR4 signaling is important in the early stage of kidney IRI, but MMF can inhibit it and improve renal function.</p>

Efficacy observation on acupuncture and moxibustion combined with hot compress of TCM herbs for scleroderma / 中国针灸

<p><b>OBJECTIVE</b>To assess the clinical efficacy and safety of surrounding needle, moxibustion and hot compress of TCM herbs for localized scleroderma.</p><p><b>METHODS</b>Forty-two cases of localized scleroderma were randomly divided into an acupuncture + herb group (23 cases, group A) and a heparin sodium group (19 cases, group B). Both the two groups were orally administrated with centella triterpenes tablets and vitamin E, group A was additionally treated with surrounding needle at local area, moxibustion at affected site and Hegu (LI 4), Zu sanli (ST 36) as well as hot external application of "hot compress herbs" at local location, while group B was treated with external application of heparin sodium cream. Both the two groups were treated for consecutive 6 months, and scores of skin sclerosis, joint pain and function were compared before and after the treatment. Also the efficacy and safety of TCM syndrome were assessed.</p><p><b>RESULTS</b>Compared with that before the treatment, the scores of skin sclerosis, joint pain and joint function in the group A after treatment were significantly decreased (all P < 0.01), the score of skin sclerosis in the group B was improved (P < 0.05), and the three types of score in the group A was obviously lower than those in the group B (both P < 0.05). The total effective rate was 86.4% (19/22) in the group A, which was superior to 52.6% (10/19) in the group B (P < 0.05).</p><p><b>CONCLUSION</b>The surrounding needle, moxibustion and external application of "hot compress herbs" could improve skin sclerosis in patients with localized scleroderma, which has obvious efficacy and relative safety.</p>

Association of two polymorphisms in ubiquitin carboxy-terminal hydrolase-L1 gene with Parkinson's disease in Shanghai / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship of polymorphisms in the ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) gene with Parkinson's disease(PD)in Shanghai Han Nationality.</p><p><b>METHODS</b>The distribution of a Serine18Tyrosine polymorphism in exon 3(C/A) and a Serine89Phenylalanine polymorphism in exon 4(C/T)of UCH-L1 gene were detected in 164 PD cases and 172 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method.</p><p><b>RESULTS</b>(1)The C allelic frequency in exon 3 of UCH-L1 gene in PD patients(62.2%) was significantly higher than that of the healthy controls(51.7%) (OR=1.53, P=0.006), as was the C/C genotype(OR=1.90, P=0.008). (2)There was no significant difference in the distribution of the C/T allele and genotypes in exon 4 between PD patients and healthy controls.</p><p><b>CONCLUSION</b>The C allele in exon 3 of UCH-L1 gene might be one of the risk factors for PD in Shanghai Han Nationality, but the polymorphisms of C/T in exon 4 showed no association with the onset of PD.</p>

Functional expression of adenylyl cyclase and phosphodiesterase in ejaculated human spermatozoa / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the differences of expressions of adenylyl cyclase (AC) and phosphodiesterase (PDE) in ejaculated spermatozoa between healthy volunteers and the patients with asthenospermia.</p><p><b>METHODS</b>Ejaculated spermatozoa were collected from healthy volunteers and the patients with asthenospermia. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of AC and PDE subtypes in human spermatozoa. The concentrations of cAMP and cGMP in the samples were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with healthy volunteers, expression of sAC mRNA and concentration of cAMP were significantly decreased in the patients with asthenospermia (P < 0.01) , while the expression of PDE4C mRNA was significantly increased at the same time (P <0.01). There were no marked differences in the expression of ACIII mRNA and concentration of cGMP between the two groups.</p><p><b>CONCLUSION</b>The sAC down-regulation and PDE4C up-regulation are possible reasons for asthenospermia.</p>

Analysis of p53 gene mutation in esophageal exfoliative cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of detecting p53 gene mutation in exfoliative esophageal cells, and compare gene mutation between precancerous lesions and normal esophageal exfoliative cells and correlate p53 gene mutation with esophageal carcinogenesis.</p><p><b>METHODS</b>Forty-eight samples (24 normal squamous epithelia and 24 severe squamous dysplasia) were obtained by balloon cytologic technique from a high incidence area, Yanting county, Sichuan Province, China in 1982. p53 gene mutations in exons 5 and 7 were analyzed by PCR-SSCP.</p><p><b>RESULTS</b>p53 genes were detected in all samples. Five samples with p53 mutation were detected in exon 7 and no mutation was detected in exon 5 in 24 severe dysplasia samples. Three of the 5 samples with mutation in exon 7 developed esophageal cancer in 1992, 1994 and 1996 respectively. No p53 gene mutation was detected in exon 5 and 7 in normal exfoliative samples.</p><p><b>CONCLUSION</b>p53 mutation may have occurred in the precancerous lesions which contributes in the initiation of human esophageal carcinogenesis.</p>