Skin-patch of Xin Huang Pian on relieving joint symptoms in patients with acute gouty arthritis: A Randomized, Double-Blind, Active-Controlled Trial.

AIMS: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis. BACKGROUND: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported. DESIGN: A Randomized, Double-Blind, Active-Controlled Trial. METHODS: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment. CONCLUSION: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate. IMPACT: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.

[Effects of Jianpi Jiedu Recipe on TCRVßCDR3 Spectratyping of Liver Cancer Rats with Pi Deficiency Syndrome].

OBJECTIVE: To observe anti-cancer effects of Jianpi Jiedu Recipe (JJR) on liver cancer (LC) rats with Pi deficiency syndrome (PDS) and its relation with the third complementary-determining region gene spectratyping of TCRVß-chain (TCRVßCDR3). METHODS: Rats were divided into 8 groups according to random digit table, i.e., the blank control group (normal), the PDS group, the LC model group, the LC-PDS group, high, middle, and low dose JJR groups (75.00, 37.50, 18.75 g/kg, respectively by gastrogavage, once per day), the thymus pentapeptide group (5 mg/kg, intramuscular injection, twice per week), 8 in each group. Rats in the normal group were administered with physiological saline by gastrogavage once per day. PDS rat model was prepared by bitter-cold purgation. LC model was prepared by orthotopic transplantation method. Twenty gene subfamilies of TCRßCDR3 in the thymus, liver, and LC tissues were detected by Gene Scan. RESULTS: High and middle dose JJR could postpone the growth of LC volume (P < 0.05), with equivalent liver index and thymus index to those of the normal group (P > 0.05). In thymus and liver tissue of the normal group, the number of clones (20 and 19), gene fragment number (220 and 113), Quasi-Gaussian distribution ratio of TCRVßCDR3 gene repertoire (100.0% and 42.1%), and fragment fluorescence peak area (6,539 ± 2,325 and 1,238 ± 439) were at the highest level among the 8 groups. TCRVßCDR3 expressions in thymus and liver tissue of high and middle dose JJR groups were approximate to those of the normal group. They were in the middle of the thymus pentapeptide group, the PDS group, the LC model group, and poorest in the LC-PDS group. TCRVßCDR3 in liver tissue expressed the best in the thymus pentapeptide group. CONCLUSION: JJR might inhibit the growth of LC cells, and its mechanism might be related to enhancing TCRVßCDR3 spectratype expression.

Total saponins from dioscorea septemloba thunb reduce serum uric acid levels in rats with hyperuricemia through OATP1A1 up-regulation.

The aim of this study is to evaluate the efficacy of total saponins of Dioscorea (TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), and organic anion transporting polypeptide 1A1 (OATP1A1) levels were measured. Comparison between the model group and treatment (allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.

[Exploring the Correlation between Pi and Shen from the Excretion of AA-I and Expressions of Or- ganic Anion Transporting Polypeptide 2al and 2 b1 in Pi Deficiency Model Rats].

OBJECTIVE: To explore the correlation between Pi and Shen by observing the relationship between the metabolism of aristolochic acid (AA) and mRNA and protein expression levels of organic anion transporting polypeptide (oatp) superfamily member 2a1 and 2 b1 (oatp2al and oatp2bl) in renal, small intestinal, and large intestinal tissues of Pi deficiency syndrome (PDS) model rats. METHODS: Totally 46 Sprague-Dawley (SD) rats were randomly divided into four groups, i.e., the blank group (n = 12), the PDS group (n = 22), the AA-I group (n = 6), and the PDS AA-I group (n = 6). PDS model was established by subcutaneously injecting Reserpine at the daily dose of 5 mg/kg for 16 successive days. Carotid intubation was performed in 6 rats selected from the blank group and the PDS group. Pharmacokinetics of AA-I were detected at 5, 15, 30, 45, and 60 min after gastrogavage of AA-I. AA-I concentrations in renal, small intestinal, and large intestinal tissues of 10 rats selected from the PDS group were determined. Normal saline was administered to 6 rats selected from the PDS group and the blank group by gastrogavage. Renal, small intestinal, and large intestinal tissues were collected in the AA-I group and the PDS AA-I group at 60 min after gastrogavage of AA-I. mRNA and protein expression levels of oatp2a1 and oatp2b1 in each tissue were detected using real-time polymerase chain reaction (RT- PCR) and Western blot. RESULTS: Compared with the blank group, plasma concentrations of in vivo AA-I were obviously higher in the PDS group at 15, 30, 45, and 60 min after gastrogavage of AA-I with statistical difference (P < 0.05). Plasma concentrations of AA-I were obviously decreased at 60 min after gastrogavage of AA-I; AA-I concentrations in renal and large intestinal tissues were elevated; AA-I concentrations in small intestinal tissues were obviously reduced in the PDS group. There was no statistical difference in mRNA expression levels of oatp2a1 and oatp2b1 in the aforesaid three tissues of rats between the blank group and the PDS group. Compared with the blank group, mRNA expression levels of oatp2a1 and oatp2b1 decreased in small intestinal tissues of the AA-I group, and the mRNA expression level of oatp2a1 in large intestinal tissues significantly decreased (P < 0.05, P < 0.01). Compared with the PDS group, mRNA expression levels of oatp2a1 and oatp2b1 increased in renal tissues of the PDS AA-I group (P < 0.05); mRNA expression levels of oatp2b1 increased in large intestinal tissues of the PDS AA-I group (P < 0.05). CONCLUSIONS: The difference in AA-I metabolism might be associated with changed expression levels of oatp2a1 and oatp2b1 in renal, small intestinal, and large intestinal tissues under Pi deficiency induced loss of transportation. Shen and Dachang played important roles in substance metabolism under Pi deficiency state, which proved Pi-Shen correlated in Chinese medical theories.

[Effect of invigorating spleen and detoxification decoction on MHC I/MHC II in spleen-deficiency liver cancer rats survival].

OBJECTIVE: To explore that Invigorating Spleen and Detoxification Decoction (ISD) enhanced the survival of spleen-deficiency liver cancer rats and the effect on major histocompatibility complex I (MHC I) and major histocompatibility complex II (MHC II). METHODS: 105 male Wistar rats were randomly divided into blank control group, liver cancer model group, spleen-deficiency model group, spleen-deficiency liver cancer model group, Thymopentin group and spleen-deficiency liver cancer model groups treated by low and high-concentration ISD for modeling and intervention. Recorded the animals' weight, survival time, moribund state and cachexia score of liver cancer rats, and collected specimens in the experiment. Immunohistochemistry and Western blot were used to detect MHC I/MHC II expression in liver tissue and liver cancer tissue. RESULTS: The cumulative survival of high concentration ISD group and Thymopentin group were higher than that of the other groups (P < 0.05), and whose cachexia score were lower than the rest (P < 0.05). In the spleen-deficiency liver cancer model groups, MHC I expression in liver tissue was higher than that in liver cancer tissue, both in these two tissues, expression of high-concentration ISD group was the strongest (P < 0.01). MHC II expression in liver cancer tissue was stronger than that in liver tissue, expression of high-concentration ISD group was the strongest in liver tissue, but in liver cancer tissue, the spleen-deficiency liver cancer model group was the strongest (P < 0.01). CONCLUSION: ISD can significantly decrease the progression of cachexia caused by transplantable tumor and prolong the survival time, the effect may be related to increasing MHC I/MHC II expression.

Observations of TCRVß Gene Expression in Rats with Dampness Syndrome.

Environmental dampness is one factor which can cause human diseases. The effects of exposure to humidity on human immune function are diverse and numerous. In the theory of traditional Chinese medicine (TCM), dampness is defined as one of the major pathogenic factors in the human body. It is divided into "external dampness" and "internal dampness." However the molecular mechanism leading to humidity-induced immunosuppression is obscure. In the present study, we investigated the expression of the T-cell antigen receptor variable ß (TCRVß) subfamilies in rats which were fed in different humid environment. And the expression levels of the TCRVß subfamilies were detected using FQ-PCR. We found that the dampness might reduce the immunological recognition function of rats. And the obstruction of the immunological recognition function might be caused by internal dampness rather than external dampness.

Acupuncture of the Five Shu Acupoints in spleen meridian to lower blood uric acid level.

BACKGROUND: Based on the principle of "spleen governing transportation and transformation", we have found that acupuncture of the Five Shu Acupoints in spleen meridian can remarkably lower the blood uric acid levels in patients with primary hyperuricemia. OBJECTIVE: To explore the clinical efficacy of the acupuncture of the Five Shu Acupoints in spleen meridian in reducing the blood uric acid level and its relevant mechanism. METHODS: A total of 32 patients with primary hyperuricemia were enrolled in this study. They were allowed to have free access to diets. The initial treatment for the concomitant diseases (but not including the therapy that might affect uric acid metabolism) was kept unchanged. The observation was formally initiated at 8:00 am on day 1. Acupuncture was not performed within the 48 hours, and only the 24-hour urine volume was recorded. The urine uric acid concentration and urinary creatinine concentration were measured from 25 to 48 hours. On the 46th hour, venous blood samples were collected to detect blood uric acid and creatinine concentrations. After the 48th hour, the patients received acupuncture of the Five Shu Acupoints in spleen meridian each morning. Once Qi was encountered, retain the needle for 30 min. The acupuncture was performed once daily for ten consecutive days. The 24-hour urine volume was recorded daily, and the fasting indicators were detected on the morning of the 11th day. RESULTS: After the acupuncture, the blood uric acid level significantly decreased in patients with increased production (overproduction) of uric acid, decreased excretion (underexcretion) of uric acid, and mixed type (all P<0.01). In the underexcretion type, the urine uric acid concentration significantly increased after the treatment (P<0.01). After the acupuncture, the fraction excretion of uric acid (FEUA) significantly increased in the underexcretion type and mixed type (P<0.01) and decreased in the overproduction type (P<0.01). After the acupuncture, the serum uric acid concentration decreased by 16.32-18.29% whereas the 24-hour urine volume increased by 24.22-29.32%. CONCLUSIONS: Acupuncture of the Five Shu Acupoints in spleen meridian can lower the blood uric acid levels by promoting uric acid excretion the and increasing urine volume.

[Organic anion transporting polypeptide (oatp4a1) mRNA and protein expressions in high fat and over-fatigue impairing Pi rats].

OBJECTIVE: To study organic anion transporting polypeptide (OATP) superfamily member 4a1 (oatp4a1) mRNA expression in the Pi deficiency model rats, thus exploring its mechanism for transporting and transforming the dampness. METHODS: Six SD rats of SPF grade were used to prepare over-fatigue impairing Pi model. Another 12 SD rats were randomly divided into the blank control group and the high fat diets group, 6 in each. The special binding tube was used for the over-fatigue impairing Pi model group on the odd day, 3 h each time. Then the rats were forced to swim in the cold water (10 degrees C +/- 1 degrees C) for 7 min on the even day, for 2 successive weeks. Rats in the model group and the blank control group were granulated feed for 12 weeks, while rats in the high fat group were fed with high fat diet for 12 weeks. All rats were free to take food and drink water. The mRNA and protein expressions of oatp4al were detected in the Fei, Pi, Gan, Shen, Wei, Xiaochang, and Dachang using Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and Western blot. RESULTS: Rats in the model group were idled together with lousy defecate and coarse skin. They ate and drank less, and lost body weight (P<0.05). They were consistent with clinical manifestations of Pi deficiency syndrome, indicating that the over-fatigue impairing Pi animal model was successfully established. Rats in the high fat group started to have poor appetite and languish spirit, move lazily and addict to sleep, have coarse, dark, and colorless hair 9 weeks later, indicating phlegm dampness syndrome. Compared with the blank control group, the average body weight increased in the high fat group at the 9th week (P<0.05). The oatp4a1 mRNA expressed in the Fei, Pi, Gan, Shen, Wei, Xiaochang, and Dachang. There was no statistical difference in the oatp4al mRNA expression among all tissues (P>0.05). The oatp4al mRNA expressions were higher in the Fei and Shen of the high fat group than in the Gan (P<0.05). CONCLUSIONS: oatp4al might be one of the basic substances in the transportation and transformation of phlegm dampness. Of them, Fei, Shen, and Dachang might play important roles in the transportation and transformation of phlegm dampness.

Expression of phosphatase and tensin homolog deleted on chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction.

AIM: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last, athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry. RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P < 0.01). The survival rate in group A, B, C was higher than in group D, and except group A with D, there was significant differences (Fisher's Exact Test P = 0.05 or 0.01). And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors (P > 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). The result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal-Wallis test, chi2 = 60.67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90, P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and chi2 = 26.08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P < 0.05, r = 0.01. respectively). However, there was no significant statistic difference between group A and group C (P > 0.05). CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.

[Clinical study of method of strengthening body resistance and disintoxication disintoxication in patients with HCC of post-TACE].

OBJECTIVE: To research the effect of a complex prescription of Chinese crude drug with the function of strengthening body resistance and disintoxication disintoxication in patients with HCC of post-TACE. METHOD: 45 patients with HCC of post-TACE, as the treatment group, were treated by a complex prescription of Chinese crude drug with the function of strengthening body resistance and disintoxication disintoxication and routine methods of protecting liver. Other 37 patients, as the control group, with the same clinical feature were treated by routine methods of protecting liver only. In the later 1 month, accumulated points of clinical symptom, hepatic function and AFP were observed in all of the patients. And the clinical effect of the two groups was compared. RESULT: One week later, in the treatment group, there is no improvement in anorexia but nausea, abdominal distention and lassitude were improved more obviously than pretherapy in both a week and one month later (P < 0.01 or P <0.05). In the control group, anorexia were improved a week later (P <0.05), but there is no improvement in nausea, abdominal distention and lassitude at the same time, and one month later all of the indexes above improved (P <0.01 or P <0.05). Accumulated points of clinical symptom was decreased more obviously in the treatment group than in the control group in both a week and one month later (P <0.05). At the end of the therapy, in the both groups, ALT, TBIL and AFP all improved except ALB, (P <0.01 or P <0.05). And TBIL improved more obviously in the treatment group than in the control one month later (P <0.05). CONCLUSION: This complex prescription of Chinese crude drug can lighten the adverse reaction of post-TACE. And also it can promote the recovery of liver function and evaluate the quality of lives of such patients.

[Expression of PTEN in athymic mice with HCC treated by complex prescription of Chinese crude drug].

OBJECTIVE: To research the treatment effect of complex prescription of Chinese crude drug in BALB/c athymic mice with human liver cancer, which were built by Bel-7402. METHOD: 48 male BALB/c athymic mouse models were built by Bel-7402 with an indirect method. After 24 hours of postoperation, the 48 athymic mice were distributed randomly into 4 groups which were treated by intragastric administration with complex prescription of Chinese crude drug that had been deliquated into 3 groups by the different density as the low, middle, and high and FT207 (Tegafur) for 4 weeks. At last, athymic mice were put to death and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry (PowerVision Two-Step Histostaining Reagent). RESULT: All of the 48 athymic mice survived 12 to 28 days (Ms 24 days) and every mouse with liver cancer demonstrated by dissection. The result of immunohistochemistry represents that the intensity of PTEN in latero-cancer tissue is the highest, and then the hepatic tissue, the lowest is cancer tissue, P < 0.01. It also represents that the intensity of PTEN in treatment groups (A, B, C) is more higher than the control group (D), P < 0.05 or P < 0.01, and group B is the highest in the treatment groups, P < 0.05 or P < 0.01. However, there is no significant statistic difference between group A and group C. CONCLUSION: The higher expression of PTEN in the laterocancer tissue can represent the protective reaction of stress of the organism. And anticancer effect of this complex prescription of Chinese crude drug relates to an eligible density of it. Mechanisms of this complex prescription of Chinese crude drug healing HCC may partially be explained by enhancing the expression of PTEN in liver.

[Study of antitumous effect of the complex prescription of Chinese crude drug in athymic mice with HCC].

OBJECTIVE: To research the treatment effect of a complex prescription of Chinese crude drug in BALB/c athymic mice. METHODS: 48 male BALB/c athymic mouse models were built by Bel-7402 with an indirect method. After 24 hours of postoperation, they were distributed randomly into 4 groups which were treated by intragastric administration with complex prescription of Chinese crude drug of different density as the low, middle, high and FF207 (Tegafur) for 4 weeks. At last, athymic mice were put to death and survial time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry. RESULTS: 4 weeks later, the total survival rate in treatment group (A + B + C) was 50% and more higher than the control group (0%) treated by FT207, P < 0.01. The survival rate in group A, B, C was higher than group D, except group A, there was significant differences, P < 0.05 or 0.01. And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors, P > 0.05. Tumor metastasis in livers of the treatment group is less than the control's, P < 0.05. Negative correlation between volume of tumors and survival time, positive correlation between tumors volume and spleen exponent were observed, P < 0.01. The result of immunohistochemistry represented that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue, P < 0.01. It also represented that the intensity of PTEN in treatment groups (A, B, C) was more higher than the control group (D), and group B was the highest in the treatment groups, P < 0.05 or P < 0.01. However, there was no significant statistic difference between group A and group C, P > 0.05. CONCLUSION: This complex prescription of Chinese crude drug can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Too large tumor volume is an main death cause of model. Mechanisms of this complex prescription of Chinese crude drug healing HCC may partially be explained by enhancing the expression of PTEN in liver.

[A clinical research of Jiawei simiaosan oral administration combined with the external application of Sihuangshuimi in the treatment of acute gouty arthritis].

OBJECTIVE: To investigate the clinical curative effect in the treatment of acute gouty arthritis with Chinese traditional medicine. METHODS: All the 65 patients of acute gouty arthritis were randomly divided into two groups. The treatment group was treated by jiawei simiaosan and combined with the external application of Sihuangshuimi. The control group was treated by gclchicine. Then an evaluation was made on the clinical effect just referring to clinical symptoms and physical sign after a week. RESULTS: Two groups were therapeutic equivalence (P >0.05). The changes of the two groups in clinical symptoms physical signs and integral signs were so obviously after treatment (P <0.01), except for the UA of control group (P >0.05). Howerer, the level of UA of the treatment group had an advantage to the control group (P <0.05). CONCLUSION: The effect of using sihuangshuimi combined with Jiawei simiaosan to cure acute gouty arthritis is not only to improve joint function and cut down UA level obviously, but also to decline the body temperature and decrease swelling to relieve pain.