Efficacy and safety of Abelmoschus manihot in treating chronic kidney diseases: A multicentre, open-label and single-arm clinical trial.

RATIONALE AND OBJECTIVE: The efficacy of Abelmoschus manihot (AM) in treating of chronic kidney disease (CKD) has been confirmed by prior trials. AM is also commonly combined to other medicines among CKD patients in clinic. This trial aimed at evaluating the safety of AM combination application, and further verifying the efficacy of AM in treating various types of CKD. STUDY DESIGN: A multicentre, prospective, open-label, single-arm trial SETTING AND PARTICIPANTS: Approximately 2000 CKD patients with proteinuria (≥ 150 mg/d), from 105 centres across China INTERVENTIONS: AM was administered to patients three times per day for 24 weeks: the daily dose was based on age (> 12 years old: 2.5 g tid; 6∼12 years old: 1.5 g tid; 2∼6 years old: 1 g tid) OUTCOMES: The efficacy outcomes were the change in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) from baseline to week 24. Safety outcomes included adverse events and laboratory tests. RESULTS: 2054 CKD patients from 105 centres were enrolled in this trial, with 1843 (89.7%) completing the 24-week follow-up. The participants' median age was 44 years old and 44.6% were female. Compared to baseline, 24-hour proteinuria decreased 471 mg (95% confident interval, 367 to 575, p < 0.001) at week 24. eGFR did not change significantly relative to baseline with the mean increase as 1.7 ml/min/1.73 m2 (95% confident interval, -0.3 to 3.7, p = 0.09). 902 (43.9%) participants combined medication to AM during follow-up. The total incidence of adverse events was 12.9%; and the most common adverse events were hyperlipidaemia (4.1%), abnormal liver function (2.3%), upper respiratory infection (1.8%), and hyperglycaemia (1.1%). Combined medications did not change the risk for hyperlipidaemia and upper respiratory infection. The combination application with antiplatelet reagents increased the risk of abnormal liver function, and with calcium channel blockers increased the risk of hyperglycaemia. LIMITATIONS: Single-arm clinical trial and short observation time CONCLUSION: We have provided safety information of AM on various types of CKD in a large trial, especially when combination to medications most commonly prescribed to CKD patients. AM also showed to decrease proteinuria with stable kidney function during follow up. AM is a promising treatment for CKD patients.

Effects of Traditional Chinese Medicine herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 to 5 years old.

OBJECTIVE: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) herbs for tonifying Qi and kidney, and replenishing spleen on intermittent asthma in children aged 2 and 5 years. METHODS: A randomized, single-blind, placebo controlled trial was conducted. Children with intermittent asthma were enrolled and their baseline conditions were measured using a questionnaire. A total of 60 participants, aged 2 to 5, were randomized into either the treatment group (n = 40) or the placebo group (n = 20). The treatment group was treated with granules of TCM herbs for tonifying Qi and kidney, and replenishing spleen, and the placebo group was given placebo granules for 3 months. The number of asthma attacks was counted and TCM syndrome scores were measured at 1, 2, 3, 6, 9, and 12 months. The airway resistance and levels of eosinophil cationic protein for the two groups were observed before and after 3 months. The results were statistically analyzed. RESULTS: Compared with the placebo group, the number of asthma attacks significantly decreased in the treatment group (P < 0.05). For the treatment group, the TCM syndrome scores decreased after 1 and 2 months; there was also a significant difference in scores between the two groups (P < 0.05). The difference remained after the medicine was stopped for 9 months (P < 0.05). After the 3-month treatment, compared with the placebo group, the airway resistance decreased in the treatment group (P < 0.05). No adverse events were reported in the treatment group. CONCLUSION: The TCM herbs for tonifying Qi and kidney, and replenishing spleen reduced the number of intermittent asthma attacks, decreased the TCM syndrome scores, and reduced the airway resistance in the children aged 2 to 5.

[Correlation Study on Pathological Characteristics of Target Organs and Excess Evil Syndrome in IgA Nephropathy].

OBJECTIVE: To explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy. METHODS: Data were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed. RESULTS: Four syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters. CONCLUSIONS: Excess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

Quinacrine synergizes with 5-fluorouracil and other therapies in colorectal cancer.

Although treatments have improved patient prognosis in surgically resectable colorectal cancer, new effective drugs with improved safety profiles are needed to improve the currently poor outcomes of patients with recurrent or metastatic colorectal cancer. Quinacrine, a small molecule anti-malarial agent that has activity in giardiasis, lupus, prion disease, and used as a means of non-surgical sterilization, has shown cytotoxic activity across a broad range of cancers. Here, we evaluate the potential of adding quinacrine to anticancer chemotherapeutics and targeted agents as a potential novel combinatorial therapy for advanced colon cancer. We show that quinacrine synergizes with 5-fluorouracil and significantly enhances the cytotoxicity of sorafenib in a panel of 10 human colorectal cancer cell lines, including those with KRAS mutations protein gel blot analysis confirmed that quinacrine's anticancer activity partially arises from its ability to stabilize p53 and lower anti-apoptotic protein levels. In a series of in vivo studies, quinacrine monotherapy lowered the tumor load of nu/nu mice bearing human colorectal cancer xenografts. In combination, quinacrine and 5-Fluorouracil significantly delayed tumor growth of a variety of different xenografts, as compared to each agent administered alone. Our results suggest that the administration of quinacrine in combination with chemotherapeutic agents and targeted agents should be further explored in patients with recurrent, locally advanced, or metastatic colorectal cancer.

FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy.

FDG (18F-deoxy-glucose) is the current gold standard for PET imaging. FLT (3'-deoxy-3'-(18F-fluorothymidine), a PET imaging marker of proliferation, has been proposed as an alternative to FDG for the assessment of therapeutic response. We examined the therapeutic predictive value of FLT-PET and FDG-PET using CALU-6, a human, p53-null, non-small cell lung cancer cell line with comparison of combined targeted therapy, TRAIL and sorafenib, versus combined conventional chemotherapy, docetaxel and cisplatin. CALU-6 tumor-bearing nu/nu mice (n=46) were evaluated in 3 therapeutic trials measuring FLT and FDG prediction of tumor response at 72 h following initiation of daily combination therapy with targeted agents, TRAIL (200 µg i.v.) and sorafenib (30 mg/kg i.p.) and compared to conventional chemotherapeutics cisplatin (3 mg/kg i.p.) and docetaxel (7.5 mg/kg i.p.). PET imaging response was compared to morphological and histological indicators of therapeutic response, including decreased vascularity (in vivo AngioSense imaging and anti-CD31 staining), slowed tumor growth (caliper measurements), decreased cellular proliferation (Ki-67 staining) and increased apoptosis (TUNEL staining). Decreases in tumor accumulation of FLT (FLTMAX -30%, p=0.03) at 72 h post treatment were observed in response to TRAIL and sorafenib combination therapy resulting in smaller, less vascular, more apoptotic tumors. No similar reduction in tumor accumulation of FLT (FLTMAX -2%, p=0.67) was observed 72 h following initiation of cisplatin and docetaxel combination therapy, despite histological and morphological evidence of drug response. In contrast, tumor imaging with FDG did demonstrate a decrease in accumulation in both treatment groups, -21% (p=0.30) in response to cisplatin/docetaxel and -8% (p=0.59) in response to TRAIL/sorafenib, but did not reach statistical significance. FLT, but not FDG, is predictive of therapeutic response to the targeted regimen TRAIL/sorafenib. However, FLT-PET may not predict therapeutic response to DNA damaging agents in p53-null tumors, likely due to loss of cell cycle control of thymidine kinase 1 (TK1). Thus, tumor imaging response by FLT may be limited in human tumors without functional p53.

[Effect of qingfei oral liquid on protein expression of transforming growth factor-beta1 and platelet derived growth factor-BB of adenovirus type 3I, 7b induced human embryonic lung fibroblast cells].

OBJECTIVE: To explore the effect of qingfei oral liquid (QOL) contained serum on protein expression of transforming growth factor-beta1 (TGF-beta1) and platelet derived growth factor-BB (PDGF-BB) of adenovirus type 3I, 7b induced human embryonic lung fibroblast cells. METHODS: The cells were divided into 5 groups, the normal cells group (NCG), the virus control group (VCG), the blank serum group (BSG), the ribavirin group (RVG) and the QOL contained serum group (QSG). All the cells except those in the NCG were challenged by adenovirus type 3I, 7b and treated with correspondent medicine. The contents of TGF-beta1 and PDGF-BB in the supernatant of cell culture were monitored by ELISA and compared among groups. RESULTS: Contents of TGF-beta1 and PDGF-BB in VCG were significantly higher, while those in QSG were significantly lower than those in VCG (P < 0.01). CONCLUSION: Adenovirus infection can increase the protein expression of TGF-beta1 and PDGF-BB of human embryonic lung fibroblast cells. QOL can decrease the protein expression of these cytokines, which maybe one of the mechanisms of its antiviral effect.