Clinical Efficacy on Addition and Subtraction Therapy of Zhibai Dihuangwan Combined with Wulingsan on Children with Refractory Nephrotic Syndrome / 中国实验方剂学杂志

Objective:This study aims to investigate the clinical effect of addition and subtraction therapy of Zhibai Dihuangwan combined with Wulingsan in the treatment of refractory nephrotic syndrome （RNS） with Yin deficiency of liver and kidney and its regulatory effect on immune inflammatory response. Method:In this study， 108 children were randomly divided into observation group （54 cases） and control group （54 cases）. Patients in two groups were treated with prednisone acetate tablets combined with tacrolimus capsules . Patients in control group took Liuwei Dihuang oral liquid， 5-10 mL/time， twice a day. Patients in control group were prescribed the addition and subtraction therapy of Zhibai Dihuangwan combined with Wulingsan， 1 dose/day. The course of treatment for both groups was 6 months. The 24 h urine total protein （24 h-UTP）， serum albumin （ALB）， serum creatinine （Scr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， low density lipoprotein （LDL）， high density lipoprotein （HDL）， liver and kidney Yin deficiency syndrome score， fibrinogen （FIB）， <italic>D</italic>-dimer （<italic>D</italic>-D）， prothrombin time （PT） and activated partial thromboplastin time （APTT） were compared before and after treatment. Also， tumor necrosis factor-<italic>α</italic> （TNF- <italic>α</italic>）， interleukin-6（IL-6）， IL-10， IL-17， CD4⁺ and CD8⁺， helper T lymphocytes17 （Th17）， regulatory T cell （Treg） were detected before and after treatment， and CD4⁺/CD8⁺andTh17/Treg were also calculated. Result:The levels of 24 h-UTP， TC， TG， LDL， FIB， <italic>D</italic>-D， TNF-<italic>α</italic>， IL-10， IL-6 and IL-17 in observation group were all lower than those in control group （<italic>P</italic><0.01）， and the levels of CD8⁺， Th17 and Th17/Treg were alsolower than those in control group （<italic>P</italic><0.05）. While the levels of HDL，ALB， CD4⁺， Treg and CD4⁺/CD8⁺ in observation group were higher than those in control group （<italic>P</italic><0.05）. The comprehensive efficacy in observation group was better than that in control group （<italic>Z</italic>=2.02， <italic>P</italic><0.05）， and the traditional Chinese medicine （TCM） syndrome efficacy of observation group was better than that of control group （<italic>Z</italic>=2.10， <italic>P</italic><0.05）. Conclusion:Based on the treatment of hormone combined with Tacrolimus， Zhibai Dihuangwan combined with Wulingsan can reduce urinary protein， improve lipid metabolism disorder and hypercoagulability， and regulate immune inflammatory reaction in patients with RNS and Yin deficiency of liver and kidney， with remarkable comprehensive effect and TCM syndrome effect.

Clinical and Experimental Research Progress of Wulingsan in Treatment of Renal Diseases： A Review / 中国实验方剂学杂志

Wulingsan， a classic prescription first recorded in the Treatise on Cold Damage （Shang Han Lun） by ZHANG Zhong-jing for patients with water retention syndrome due to the disturbance of Qi transformation in bladder， has often been modified by ancient and modern doctors for the treatment of renal diseases. It produced satisfactory outcomes without inducing adverse reactions. The databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， and PubMed were searched for articles concerning the clinical application and pharmacological mechanism of Wulingsan in the treatment of renal diseases published by domestic and foreign scholars in recent years. The summary of the included articles revealed that Wulingsan has been widely employed for the treatment of renal edema， diabetic nephropathy， acute and chronic glomerulonephritis， nephrotic syndrome， renal insufficiency， abnormal urination， etc.， and the resulting outcomes were satisfactory. Wulingsan alone or in combination with western medicine yielded better clinical outcomes than the western medicine alone. In the exploration of its pharmacological mechanism， there existed some individual reports by Korean scholars， while Chinese scholars tended to work as a team. After years of research， each team has found that Wulingsan was superior to Wulingsan decoction in excreting water， which might be related to the absence of massive low-polarity and volatile components in the decoction that were responsible for regulating the expression of aquaporins （AQP） in kidney of saline-loaded rats. Wulingsan regulates the endocrine state of rats with kidney yang deficiency， inhibits the reabsorption of water， increases the activity of Na+-K+-ATPase， and reduces the expression of AQP 1， AQP 2， AQP 3， and AQP 4. Besides， it bi-directionally regulates the human water metabolism， which is achieved via the dual-directional regulation of purinergic P2X3 receptor expression on bladder detrusor. The efficacy of Wulingsan in treating chronic renal failure is attributed to its protection against the damaged renal tissue，structure and fanction. Hence， this paper summarized the research progress of Wulingsan in the treatment of renal diseases in recent years， aiming to provide a reference for the clinical and basic exploration of Wulingsan against renal diseases in the future.

Effect of Xiao Chaihutang and Wulingsan on Protection of Residual Renal Function in Patients with Maintenance Peritoneal Dialysis and Effect on Peritoneal Fibrosis and Micro-inflammation / 中国实验方剂学杂志

Objective: To observe the protective effect of Xiao Chaihutang and Wulingsan on residual renal function in patients with maintenance peritoneal dialysis (PD) and investigate its effect on peritoneal fibrosis and microinflammation.Method: The 65 patients with PD who were admitted to our hospital from June 2016 to June 2017 were enrolled in the study, and divided into control group (32 cases) and study group (33 cases) according to the random number table. The control group received routine treatment. The study group received routine treatment+Xiao Chaihutang and Wulingsan. The fasting venous blood was taken before treatment and 3 months after treatment to measure serum creatinine (SCr) and urea nitrogen (BUN). Urine was collected; 24 hour urine volume was recorded; 24 h urine protein (24 h UP) was measured by colorimetry; glomerular filtration rate (eGFR) was calculated; residual renal function (RRF) was expressed with residual renal creatinine clearance. Inflammatory factors were detected by using chemiluminescence, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels. Serum Janus Kinase (JAK) 2 as well as signal transducer and activator of transcription (STAT) 3 levels were determined by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). E-cadherin and α-smooth muscle actin (α-SMA) levels were determined by Western blot.Result: Before treatment, there was no significant difference in the residual renal function between two groups. After treatment, the residual renal function of the study group was significantly better than that of control group (PPα in study group were lower than those in control group (PPPα-SMA protein was significantly increased after treatment (Pα-SMA protein after treatment.Conclusion: Xiao Chaihutang and Wulingsan can protect the residual renal function of PD patients, and the mechanism may be related to the improvement of peritoneal fibrosis and the reduction of micro-inflammation of the body, showing a high application value.

Mechanism of Wulingsan in Treatment of Rheumatoid Arthritis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To study the mechanism of Wulingsan (WLS) in the treatment of rheumatoid arthritis (RA) by network pharmacology. Method:The active components of WLS were screened on traditional Chinese medicine systems pharmacology(TCMSP) platform, and the targets were predicted in DragBank database. The "component-target" network was constructed by Cytoscape 3.2.1 software. Disease targets were searched in TTD, DrugBank and DisGenet databases. The Venn diagram was built to extract the target of WLS in the treatment of RA, and the gene oesthetics(GO) function annotation and Kyoto Encyclopedin of Genes and Genomes(KEGG) signal pathway enrichment analysis were performed by cluego plugin. The TCM-component-target-pathway network of WLS was constructed, and the network feature analysis was made by Network Analyzer. Result:Totally 52 components and 297 potential targets in WLS and 1 845 targets relating to RA were excavated, and 49 common targets of WLS-RA were obtained. The common targets were mainly enriched in 322 biological processes and 31 signaling pathways. Conclusion:WLS may regulate targets, such as prostaglandin epoxide synthase 2 (PTGS2), transforming growth factor-β1 (TGF-β1), cysteine aspartate protein-3 (Caspase-3), transcription factor p65 (RELA), progesterone receptor (PGR), and adjust cancer-related pathways, tumor necrosis factor(TNF) signaling pathways, interleukin-17(IL-17) signaling pathways, nuclear factor-κB(NF-κB) signaling pathways, Th17 cell differentiation, so as to inhibit the inflammatory response, regulate immune function and adjust apoptosis to treat rheumatoid arthritis.

Differences between the Effects of Sho-saiko-to, Gorei-san and Toki-shakuyaku-san on the Sphincter of Oddi. An intraoperative cholangiomanometric study / 日本東洋医学雑誌

Female patients suffering from gallbladder stone disease were administered Sho-saiko-to (Xiao-Chai-Hu-Tang), Gorei-san (Wu-Ling-San) or Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) preoperatively, and were examined by cholangiomanometry during operation. Perfusion pressure was significantly elevated, when Sho-saiko-to or Gorei-san were administered, meaning that the pressure threshold of the sphincter of Oddi for volume load in the bile duct was lowered. This phenomenon tended to be more obvious in Gorei-san group, and will prevent duodenal fluid from transpapillary reflux. Parameters concerning the declining curve (T_1/2, T_1/4, T_1/5) showed a significantly rapid relaxation of the sphincter of Oddi only in Sho-saiko-to group, which will result in a prevention of stasis of bile. These modulating functions of Sho-saiko-to and Gorei-san for the sphincter of Oddi would be one of the main reasons why these formulas are used for hypochondriac fullness and distress or excessively accumulated intestinal fluid. Toki-shakuyaku-san showed no such effects on the sphincter of Oddi.