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.

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection / 中华医学杂志(英文版)

BACKGROUND@#Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.@*METHODS@#We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.@*RESULTS@#Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.@*CONCLUSION@#This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

Values of combination of urinary L-FABP and NGAL in early diagnosis of acute kidney injury after cardiac surgery in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the values of combination of urinary liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in children.</p><p><b>METHODS</b>A total of 97 children with congenital heart disease undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples were collected before and after surgery. Levels of serum creatinine (Scr), urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79) were measured, and the postoperative dynamic changes in these markers were compared between the two groups. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to assess the values of these markers alone or in combination in the prediction of postoperative AKI.</p><p><b>RESULTS</b>The levels of urinary L-FABP and NGAL in the AKI group were significantly higher than those in the non-AKI group at 2 and 6 hours after surgery, and the changes in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896 respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively. Those of their combination were 0.942 and 0.929 respectively.</p><p><b>CONCLUSIONS</b>Urinary L-FABP and NGAL significantly increase in the early stage of AKI after cardiac surgery in children, which are significantly earlier than the changes in Scr. They can be used to predict the occurrence of AKI in the early stage. A combination of the two biomarkers can further improve the accuracy of diagnosis.</p>

Clinical observation on two-way quintuple puncture in the treatment of ganglion / 中国针灸

<p><b>OBJECTIVE</b>To explore the better therapy in the treatment of ganglion.</p><p><b>METHODS</b>Ninety cases of ganglion were randomized into a two-way quintuple puncture group, a common quintuple puncture group and a fire needling group, 30 cases in each one. In the two-way quintuple puncture group, the "9-in-1" multiple penetrating needling technique was used. In the common quintuple puncture group, the traditional "5-in-1" multiple penetrating needling technique was applied. In the fire needling group, the traditional multiple fire needling technique was adopted. The treatment was given once a day, 3 treatments made one session and the efficacy was analyzed statistically after 1 session treatment in the three groups.</p><p><b>RESULTS</b>All of the three therapeutic methods achieved the efficacy on ganglion. The curative rate was 96. 7% (29/30) in the two-way quintuple puncture group, which was better obviously than 66.7% (20/30) in the common quintuple puncture group and 60. 0% (18/30) in the fire needling group (both P<0. 01).</p><p><b>CONCLUSION</b>The two-way quintuple puncture technique achieves the remarkably superior efficacy on ganglion as compared with the common quintuple puncture technique and fire needling technique.</p>

Adhesive and invasive effects and mechanism of neiyi recipe on the endometriosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the inhibitory effects of Neiyi Recipe by comparing adhesive and invasive effects of eutopic and ectopic endometrial tissues from endometriosis women and the endometrium from endometriosis-free women.</p><p><b>METHODS</b>The invasive capacity of endometrial stromal cells from endometriosis-free women, eutopic and ectopic endometrial stromal cells from women with endometriosis were compared using Boyden chamber, the chick chorioallantoic membrane (CAM) ectopy transplant, and immunohistochemical EnVision method. The expressions of adhesion and invasion correlated cytokines in the transplanted tissue and effect of Neiyi Recipe on them were observed.</p><p><b>RESULTS</b>The numbers of invasion stromal cells of eutopic and ectopic endometrial tissues were obviously more than those in the endometriosis-free women (P<0.05). After treatment with Neiyi Recipe and danazol respectively, the number of invasion stromal cells was significantly less in the Neiyi Recipe group than in the danazol group (P<0.05). Compared with endometriosis-free women, the expression of ICAM-1 in the ectopic endometrium tissue, and MMP-9 expressions in the eutopic and ectopic endometrium were significantly higher (all P<0.05) and TIMP-1 expressions obviously lower (P<0.01). In the eutopic endometrium, Neiyi Recipe and danazol serum could significantly lower the expression of MMP-9, and up-regulate expressions of TIMP-1 and ICAM-1 (P<0.01). In the ectopic endometrium, Neiyi Recipe could significantly lower the expression of MMP-9 (P<0.01) and ICAM-1 (P<0.05), and danazol serum could lower the expression of ICAM-1 (P<0.05). Compared with danazol, Neiyi Recipe showed more obvious effect in down-regulating MMP-9 (P<0.05).</p><p><b>CONCLUSIONS</b>High expression of MMP-9 and low expression of TIMP-1 existed in eutopic and ectopic endometrial tissues of endometriosis, which could enhance the ectopic invasion and transplant of endometrial cells. Neiyi Recipe could inhibit the invasion of endometrial stromal cells and the expression of MMP-9.</p>

Fosinopril up-regulates and ameliorates the Ang II induced down-expression of klotho gene in NRK-52E / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene.</p><p><b>METHODS</b>Culture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively.</p><p><b>RESULTS</b>Fos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E.</p><p><b>CONCLUSION</b>Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.</p>

Effect of spironolactone on the expression of Toll-like receptor 4 in renal tubular epithelia cells exposed to high glucose / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the expression of Toll-like receptor 4 (TLR4) in renal tubular epithelial cells exposed to high glucose and the effect of spironolactone on the TLR4 expression.</p><p><b>METHODS</b>In vitro renal tubular epithelial cells (NRK-52E) were randomly exposed to DMEM culture solution with low glucose (5 mmol /L), high glucose (25 mmol/L) or 10(-7) mol/L spironolactone plus 25 mmol/L glucose. Immunohistochemistry, RT-PCR and Western blot were used to determine TLR4 protein and mRNA expression. The levels of IL-6 and TNF-alpha in the cell culture supernatant were determined using ELISA.</p><p><b>RESULTS</b>The expression of TLR4 mRNA in the high glucose group began to increase 6 hrs and remained at a higher level up to 24 hrs after exposure as compared with the low glucose group. The TLR4 mRNA expression in the spironolactone treatment group was significantly lower than that in the high glucose group, although it was higher than that in the low glucose group between 6 and 24 hrs after exposure. TLR4 protein expression increased significantly in the high glucose group 24 and 48 hrs after exposure compared with that in the low glucose group. The TLR4 protein expression in the spironolactone treatment group was lower than that in the high glucose group, but higher than that in the low glucose group. IL-6 and TNF-alpha expression in the supernatant from the NRK-52E cells in the high glucose groups increased significantly as compared with the low glucose group. The spironolactone treatment group had significantly reduced IL-6 and TNF-alpha expression compared with the high glucose group.</p><p><b>CONCLUSIONS</b>High glucose triggers an increase in the expression of TLR4 and inflammatory factors in NRK-52E cells. TLR4 may participate in the progress of diabetic nephropathy. Spironolactone can reduce expression of TLR4 and inflammatory factors, which might be attributed to one of the mechanisms of protection by spironolactone against diabetic nephropathy.</p>

Effects of fosinopril and losartan on the expression of Toll- like receptor 4 in renal tubular epithelia cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the mechanism of Toll-like receptor 4(TLR4) in hypertensive renal injury and the protective effect of fosinopril(Fos) and losartan(Los).@*METHODS@#NRK-52E was incubated into 5 groups: NRK-52E (normal control), NRK-52E+AngII, NRK-52E+AngII+Fos(10(-5) mmol/L),and NRK-52E+AngII+Los(10(-5) mmol/L), NRK-52E +AngII+Fos(10(-5) mmol/L)+Los(10(-5) mmol/L). TLR4-specific RNAi plasmids were stably transfected into NRK-52E. After 24 h, TLR4, IL-6, and TNF-alpha mRNAs were examined by reverse transcription-polymerase chain reaction(RT-PCR). TLR4 proteins were detected by Western blot, NF-kappaB nuclear translocations were tested by immunocytochemistry,and IL-6 and TNF-alpha supernatant levels were tested by enzyme linked immuno-sorbent assay(ELISA).@*RESULTS@#TLR4, NF-kappaB, IL-6,and TNF-alpha were highly expressed in AngII induced NRK-52E(P<0.01). In NRK-52E that was stably transfected TLR4-special RNAi plamids, TLR4 protein and mRNA expression were obviously inhibited(P<0.05). After stimulation by AngII, the TLR4, IL-6, TNF-alpha levels in the stabe transfection group were increased compared with the normal group(P<0.05). Fos or/and Los down-regulated TLR4, IL-6, and TNF-alpha expressions(P<0.05), but no cooperation was observed.@*CONCLUSION@#TLR4 may lead to inflammatory reaction in hypertensive renal injury. Fos or/and Los can decrease the expressions of TLR4 and correlate inflammatory factors, which may be part of the renal protective mechanism.

Clinical study on effect of Bushen Huayu Qutan Recipe in treating polycystic ovarian syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect and the possible mechanism of Bushen Huayu Qutan Recipe (BHQR, a Chinese recipe formulated according to the therapeutic principle of nourishing Shen, resolving stasis and dispelling phlegm) on polycystic ovarian syndrome (PCOS).</p><p><b>METHODS</b>BHQR was used, both internally and externally, to treat 46 patients with PCOS, and combined with diformin if necessary. Six successive months treatment was regarded as one course. The clinical symptoms and signs, including obesity, polytrichia, acne and acanthosis, were observed and scored before and after treatment; and serum levels of hormones and insulin were measured as well.</p><p><b>RESULTS</b>After treatment, the scores of symptoms and signs of patients were significantly lowered (P<0.05 for obesity and P <0.01 for others), significant lowering was also found in serum level of testosterone (P<0.05), fasting serum insulin (P<0.01) and the values of insulin and insulin area under curve (P<0.05) 30 min and 60 min after glucose load.</p><p><b>CONCLUSION</b>BHQR could not only significantly relieve the symptoms and signs of patients with PCOS, but also regulate well the ovarian function.</p>

Changes of podocyte ultrastructure and expression of podocyte-associated molecules in rats with diabetic nephropathy / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of podocyte ultrastructure and changes of nephrin and the podocin expression on the pathogenesis of diabetic nephropathy (DN) in rats.@*METHODS@#Twenty Wistar rats were divided into 2 groups: a normal control group and a DN model group.We determined the 24h proteinuria and other biochemical indexes, measured the ultrastructures of podocytes with electronic microscope, and detected the expression of nephrin and podocin with immunohistochemical technique and RT-PCR at the 4th and 8th weeks.@*RESULTS@#The 24h proteinuria increased in the DN group; the number of podocytes was significantly lower; and the foot process width (FPW) obviously increased in the DN group compared with the normal group (P<0.01). The protein and mRNA expressions of nephrin and podocin reduced in the DN group.There was a negative correlation between the proteinuria and the protein expression of nephrin and podocin (P<0.01).@*CONCLUSION@#The reduction in glomerular podocyte number,the increased FPW, and the down-regulated expression of nephrin and podocin appear at the early stage of DN and become more serious with the disease progression.The podocyte lesion not only is associated with the degree of proteinuria,but also correlates with the development of glomerulosclerosis and damage of renal function.

Application of continuous renal replacement therapy in the rescue of MODS patients / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of continuous renal replacement therapy (CRRT) on patients with emergency and serious diseases.@*METHODS@#The patients were divided into 2 groups: Group A [71 patients with multiple organ dysfunction syndrome (MODS)] were treated by CRRT for 175 times. Group B (30 patients) were treated with common hematodialysis (HD). Blood urea nitrogen (BUN), serum creatinine (Scr), natrem (Na(+)), kalium (K(+)), chlorine (Clj), power of hydrogen (pH), bicarbonate (HCO3-), carbon dioxide partial pressure (PCO(2)), and oxygen pressure (PO(2)) were measured before and after the treatment.@*RESULTS@#After the treatment, all patients' general state of health, water-electrolyte and acid base disorder were improved. The levels of BUN, Scr, K(+) (All P(s)<0.01), and Na(+) (P<0.05 in Group A, P<0.01 in Group B) were all lower and the levels of CO(2)CP (P<0.01 in Group A, P<0.05 in Group B) were higher than that before the pretherapy in both Group A and Group B. There was significant difference on the levels of BUN, Scr, K(+)(All P(s)<0.01), Cl(-) and CO(2)CP (All P(s)<0.05) between Group A and Group B, which indicated the therapeutic effect in Group A was better than that in Group B. Furthermore, the levels of pH, PO(2) and HCO(3)(-) were higher (P<0.01) and PCO(2) was lower (P<0.05) obviously than that before the CRRT in 30 patients with acute respiratory distress syndrome (ARDS) in Group A. Among the 9 patients with poisoning, 7 were alleviated completely and 2 died after the CRRT plus hemoperfusion (HP). The survival time of patients was lengthened in Group A. No blood or bleed aggravation occurred in patients with bleeding inclination or 48 h before the operation after using the method of heparin soaking the blood filter.@*CONCLUSION@#CRRT has better curative effect on removing the toxin effectively, rapidly correcting the turbulence of water electrolyte and sour-alkali balance for patients compare with HD. At the same time, it can increase the level of PO(2) and reduce CO(2) retention, improve the lung function and brain edema, and increase the patient's survival rate. Using CRRT as early as possible is very important and it can improve the prognosis of the patients who had MODS or other dangers because the death rate of MODS patients is very high.

Continuous veno-venous hemofiltration treatment for acute hypernatremia / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of continuous veno-venous hemofiltration (CVVHF) for acute hypernatremia.@*METHODS@#Seven patients with hypernatremia were studied and treated with CVVHF. The serum sodium concentration and its remedy speed, creatinine, osmolarity, and blood pressure, etc were observed before and after CVVHF.@*RESULTS@#The patients were treated with CVVHF averagely for 40 hours. The serum sodium concentration, creatinine, osmolarity after the treatment decreased significantly and the APACHE II scores significantly improved. Among the 5 coma patients, 2 patients's consciousness was improved.@*CONCLUSION@#CVVHF is effective and can be a new method for treating acute hypernatremia.