Regulation of Yes associated protein in diabetic nephropathy mice by Yishen Huashi Granule / 中国药理学通报

Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin / 中国中药杂志

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.</p><p><b>METHODS</b>Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.</p><p><b>RESULTS</b>In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.</p><p><b>CONCLUSIONS</b>Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.</p>

Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.</p><p><b>METHODS</b>Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.</p><p><b>RESULTS</b>Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.</p><p><b>CONCLUSIONS</b>The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.</p>

Clinical observation of Shen No. 9 Recipe with Qingre Moshen Granule on the treatment of idiopathic membranous nephropathy after treated by multiple Western drugs with no efficacy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Shen No. 9 Recipe (SR) combined with Qingre Moshen Granule (QMG) in treatment of idiopathic membranous nephropathy (IMN) patients with no efficacy after treated by hormone or immunosuppressive agent, and further to explore the possible mechanism of this method in treatment of IMN by detecting the cellular immune function and cytokine interleukin-2 (IL-2).</p><p><b>METHODS</b>Forty-four IMN patients with no efficacy after treated by multiple Western drugs were recruited from October 2007 to October 2009. They took SR (one dosage daily, oral administration in two portions) and QMG (each package each time, thrice daily) for 24 weeks. The 24-h urine protein, glomerular filtration rate (GFR), plasma albumin (Alb), serum creatinine (SCr), urea nitrogen (BUN), triglyceride (TG), serum total cholesterol (TC), levels of cellular immune function (CD4+, CD8+, CD4+/CD8+ ratio), and IL-2 were detected before and after treatment. The changes of Chinese medicine syndrome and adverse reactions were observed and recorded.</p><p><b>RESULTS</b>After treatment the complete remission rate, the basic remission rate, and the total effective rate was 4.5%, 68.2%, 84.1%, respectively. The total markedly-effective rate of Chinese medicine syndrome was 90.9%. The Chinese medicine syndrome was significantly lower than before treatment (P < 0.01). The 24-h urine protein obviously decreased (P < 0.01), Alb obviously increased (P < 0.01), levels of TC and TG obviously decreased (P < 0.01, P < 0.05). There was no obvious change in levels of SCr and BUN (P > 0.05). The GFR significantly increased (P < 0.05). CD4+ and the ratio of CD4+/CD8+ were obviously elevated (P < 0.01) and the CD8+ obviously decreased (P < 0.01). The expression level of IL-2 obviously increased, but it still was lower than the normal value, showing statistical difference (P < 0.01).</p><p><b>CONCLUSIONS</b>SR + QMG showed definite efficacy in treatment of IMN patients with no efficacy after treated by multiple Western drugs. It could improve the level of cellular immunity and improve abnormal expression levels of IL-2.</p>

Researches on the establishment of chronic nephropathy models and the effect of TCM on these models / 中国中西医结合杂志

Following contents were reviewed in this article: More and more experimental studies related with chronic uratic nephropathy were carried out in recent years. In most of these studies, the animal models were established mainly from viewpoints of gene recombination, urinary uric acid inhibition and blood uric acid production promoting. TCM showed good effects in lowering blood uric acid, regulating levels of cytokines and postponing interstitial fibrosis. However, further studies on Chinese herbs and their extracts is necessary.

Clinical study on treatment of mid-advanced crescentic nephritis by qingre huoxue recipe / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of integrative Chinese and Western medicine in treating mid-advanced crescentic nephritis (MACN).</p><p><b>METHODS</b>Thirty-two patients, their diagnosis was confirmed as MACN by renal biopsy, were divided, adopting randomized, controlled method, into two groups, the treated group and the control group, they were all, excepting one, treated with impact therapy of methyl-prednisolone followed with oral intake of prednisone, to part of them cyclophosphamide or mycophenolate mofetil was given in addition, to those with hypo-hemoglobin (< 90 g/L), subcutaneous injection of erythropoietin was administered. Decoction of Qingre Huoxue recipe (QHR), consisted of oldenlandia herb 30 g, honey-suckle stem 30 g, violet herb 30 g, red peony root 15 g, rehmannia root 15 g, solomonseal rhizome 15 g, asiabell root 30 g, red sage root 30 g, prepared rhubarb 12 g and giant-hyssop herb 12 g, were additionally given one dose per day to patients in the treated group. The renal function, improvement of anemia and immunosuppressive agents needed in patients were observed after 3 months treatment.</p><p><b>RESULTS</b>After treatment, renal function was improved in both groups, but the effect in the treated group was better than that in the control group (P < 0.05). Anemia was partially alleviated in the two groups with no significant difference. The dosage of glucocorticoids used in the treated group was obviously lesser than that used in the control group (P < 0.01).</p><p><b>CONCLUSION</b>Integrative Chinese and western medicine could treat crescentic nephritis to obtain good effect, and reduce the quantity of glucocorticoid necessity for treatment.</p>