Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis.

Liver fibrosis is a leading contributor to chronic liver diseases such as cirrhosis and liver cancer, which pose a serious health threat worldwide, and there are no effective drugs to treat it. Qijia Rougan decoction was modified from Sanjiasan, a traditional Chinese medicine (TCM) described in the "Wenyilun" manuscript. Qijia Rougan decoction possesses hepatoprotective and antifibrotic effects for clinical applications. However, its underlying mechanisms remain largely unknown. In this study, fibrotic rats induced by carbon tetrachloride (CCl4) were treated with two doses of Qijia Rougan decoction. Histopathological and serum biochemical analyses were carried out to assess liver structure and function, respectively. High-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) was performed to identify bioactive compositions in Qijia Rougan decoction. Transcriptome analysis using mRNA-sequencing (mRNA-Seq) was used to explore the underlying mechanisms and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Qijia Rougan decoction significantly attenuated CCl4-induced hepatic fibrotic injury, supported by promoted liver function and improved liver fibrosis. Eight main representative components originating from raw materials in the Qijia Rougan decoction were found to possess an antifibrotic role. Mechanistically, Qijia Rougan decoction regulated biological processes such as oxidation-reduction, fatty acid metabolism, cell adhesion, and transforming growth factor beta (TGFß) signaling. We determined that Qijia Rougan decoction reversed the expression of inflammatory cytokines and inhibited the activation of fibrosis-related TGFß signaling. It also reversed the deterioration of liver structure and function in rats induced by CCl4. Overall, Qijia Rougan decoction significantly mediated metabolism-associated processes, inhibited inflammatory reactions, and repressed fibrosis-related TGFß signaling, which prevented liver fibrosis deterioration. Our study deepens our understanding of TCM in the diagnosis and treatment of liver fibrosis.

Study on efficacy and safety of Huangqi Guizhi Wuwu decoction treatment for oxaliplatin induced peripheral neurotoxicity: A protocol for a randomized, controlled, double-blind, multicenter trial.

BACKGROUND: Oxaliplatin can cause severe peripheral neurotoxicity, which is an important reason for clinical oxaliplatin reduction and cessation of treatment. Oxaliplatin induced peripheral neurotoxicity (OIPN) can cause paresthesia and dysesthesia, even affect the quality life of patients. So far, there are no recognized and effective measures to prevent OIPN. Huangqi Guizhi Wuwu decoction is a classical prescription of ancient Chinese medicine recorded in "the synopsis of the Golden Chamber," which can be used in the treatment of various neurotoxicity. However, there is a lack of large-scale and high-quality clinical studies on the prevention of OIPN by Huangqi Guizhi Wuwu decoction. The purpose of this study is to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction on preventing OIPN. METHODS/DESIGN: This study is a randomized, controlled, double-blind, and multicenter clinical trial. Three hundred sixty patients will be randomly assigned into Huangqi Guizhi Wuwu decoction group and Huangqi Guizhi Wuwu decoction mimetic agent group. Patients will receive chemotherapy with FOLFOX of 8 cycles of 3 weeks with Traditional Chinese Medicine (TCM) for 6 months and 1-year follow-up. The primary outcome measure is the differences in the incidence of chronic neurotoxicity of grade 2 and above during and after treatment. The secondary outcome measure is the improvement in other symptoms associated with chemotherapy. Four methods will be used to evaluate the efficacy of neurotoxicity, including oxaliplatin specific toxicity grading standard (Levi classification); CTCAE4.02 version; EORTC QLQ-CIPN20 scale, EORTC QLQ C30 scale, and EORTC QLQ-CR29 scale are used at the same time; Electromyography. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Huangqi Guizhi Wuwu Decoction on preventing OIPN. TRIAL REGISTRATION: Clinical Trials.gov (Identifier: NCT04261920).

Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice.

BACKGROUND: Chemoresistance is a major obstacle that limits the benefits of 5-Fluorouracil (5-Fu)-based chemotherapy for colon cancer patients. Autophagy is an important cellular mechanism underlying chemoresistance. Recent research advances have given new insights into the use of natural bioactive compounds to overcome chemoresistance in colon cancer chemotherapy. As one of the multitargeted and safer phytomedicines, curcumin has been reported to work as cancer-specific chemosensitizer, presumably via induction of autophagic signaling pathways. The precise therapeutic effect of curcumin on autophagy in determining tumorous cells' fate, however, remains unclear. This study was conducted to investigate the differential modulations of the treatments either with 5-Fu alone or 5-Fu combined with curcumin on cellular autophagic responses and viabilities in the human colon cancer cells HCT116 and HT29, and explore molecular signaling transductions underlying the curcumin-mediated autophagic changes and potentiation of 5-Fu's cytotoxicity in vitro and in vivo. METHODS: Cell proliferation assay and morphology observation were used to identify the cytotoxicity of different combinations of curcumin and 5-Fu in HCT116 and HT29 cells. Cell immunofluorescence assay, Flow cytometry and Western blot were employed to detect changes of autophagy and the autophagy-related signaling pathways in the colon cancer cells and/or xenograft mice. RESULTS: Curcumin could significantly augment the cytotoxicity of 5-Fu to the tumorous cells, and the pre-treatment with curcumin followed by 5-Fu (pre-Cur) proved to be the most effective one compared to other two combinations. The chemosensitizing role of curcumin might attribute to the autophagy turnover from being activated in 5-Fu mono-treatment to being inhibited in the pre-Cur treatment as indicated by the changes in expression of beclin-1, p62 and LC3II/LC3I and the intensity of Cyto-ID Green staining. The autophagic alterations appeared to be contributed by down-regulation of not only the phospho-Akt and phospho-mTOR expressions but the phospho-AMPK and phospho-ULK1 levels as well. The cellular activation of AMPK by addition of A-769662 to the pre-Cur combination resulted in reversed changes in expressions of the autophagy protein markers and apoptotic status compared to those of the pre-Cur combination treatment. The findings were validated in the xenograft mice, in which the tumor growth was significantly suppressed in the mice with 25-day combination treatment, and meanwhile expressions of the autophagy markers, P-AMPK and P-ULK1 were all reversely altered in line with those observed in HCT116 cells. CONCLUSION: Pre-treatment with curcumin followed by 5-Fu may mediate autophagy turnover both in vitro and in vivo via AMPK/ULK1-dependent autophagy inhibition and AKT modulation, which may account for the increased susceptibility of the colon cancer cells/xenograft to the cytotoxicity of 5-Fu.

[Nasal resorption of prim-O-glucosylcimifugin and 5-O-methylvisammioside in rats].

In this experiment, rat nasal mucosa absorption characteristics of prim-O-glucosylcimifugin and 5-O-methylvisammioside were studied to provide a basis for drug delivery of Toutongning nasal spray. The nasal mucosa absorption test in rats was conducted with in situ nasal perfusion method after pH 6 buffer solution was used to prepare high, medium and low concentrations of prim-O-glucosylcimifugin, 5-O-methylvisammioside mixed solution as liquid circulation in nasal cavity. Then the concentrations of the circulating liquid compositions to be measured were determined by HPLC, and the absorption rates of prim-O-glucosylcimifugin and 5-O-methylvisammioside under different pH conditions were also investigated. According to the results, the absorption rate constant was (0.588±0.041)×10⁻³, (0.547±0.023)×10⁻³, (0.592±0.063)×10⁻³ min⁻¹ for prim-O-glucosylcimifugin high, middle and low concentrations, and (0.438±0.041)×10⁻³, (0.407±0.023)×10⁻³, and (0.412±0.063)×10⁻³ min⁻¹ for 5-O-methylvisammioside high, middle and low concentrations. There was no significant difference among high, middle and low concentration groups, and the absorption under pH 6 was better than that under other pH conditions. Therefore, we can get the conclusion that the main active ingredient of Toutongning nasal sprays can be absorbed through the nasal mucosa, and it is feasible to make nasal spray; in addition, pH 6 of nasal spray is scientific and reasonable.

[Characteristics and influencing factors of phosphorus adsorption on sediment in Lake Taihu and Lake Hulun].

Lake Taihu and Lake Hulun in southern and northern China were selected for the investigation of differences in the characteristics and influencing factors of phosphorus (P) adsorption on the sediments of these two lakes by laboratory simulation experiment. The results showed that: (1) The P adsorption capacity of sediment in Lake Taihu was much higher than that in Lake Hulun, and the maximum adsorption capability for the sediments in these two lakes was 1428.57 mg x kg(-1) and 56.81 mg x kg(-1), respectively; (2) Compared with the sediments in Lake Hulun, the particle diameters from sediments in Lake Taihu were much smaller, and their specific surface areas were much larger, so their P adsorption capacity were much higher; (3) The equilibrium adsorbed amounts in these two lakes were correlated with the total amounts of Al, Fe, Mn (P < 0.05) and significantly correlated to the contents of active Al, Fe, Si, Mn (P < 0.01). However, there was significant negative correlation between the equilibrium adsorbed amounts and total Si contents for the sediments in these two lakes (P < 0.01); (4) The P adsorption capacity decreased as pH values in the overlying water increased, and the increase of pH values affected the adsorption behavior of phosphorus on the sediments in Lake Taihu much more obviously. Therefore, the characteristics of sediments and the variations of pH values in the overlying water affected the adsorption behavior of P on sediments in lake water body.

[Study of different enteral nutrition formulation treatment after esophagectomy].

OBJECTIVE: To compare the efficiency of different early enteral nutrition (EN) with Ensure, Nutrison, and Peptison in postoperative patients with esophageal carcinoma. METHODS: A total of 45 postoperative patients with esophageal carcinoma were randomly divided into three groups using random digit table: Ensure group (n=15), Nutrition group (n=15), and Peptison group (n=15). Enteral nutrition was given using nasogastric tube from the 2nd postoperative day for 8 days. Albumin and prealbumin were detected on the day before surgery and postoperative day 9 after fasting. The time to gastrointestinal tract function recovery, complications, and the cost of enteral nutrition were compared among the three groups. RESULTS: There were no significant differences in postoperative nutrition indices(albumin and prealbumin) and EN-related complications among the three groups(all P>0.05). The time to gastrointestinal tract function recovery in Ensure group [(52.4±15.7) h] and Nutrison group [(50.8±12.4) h] was less than that in Peptison group [(60.3±16.8) h] (P<0.05). The expense of Ensure group [(443.3±45.8) RMB] was obviously less than that of Nutrison group[(639.5±52.6) RMB] and Peptison group [(990.5±95.5) RMB](both P<0.01). CONCLUSIONS: Ensure, Nutrison and Peptison can be used for postoperative early enteral nutrition in patients with esophageal carcinoma, and the efficacy and complication are comparable. The cost of Ensure is the lowest.

[Effect of disturbance on growth of Microcystis aeruginosa in different nutrient levels].

The specific growth of Microcystis aeruginosa was studied under different nutrient levels and different disturbance in laboratory. It is shown that the algae get better growth under disturbance than stationary state in oligotrophic nutrient water, the specific growth rate can increase from 0.1 d(-1) to 0.3 d(-1). The algae can get the maximum specific growth rate under the wind speed of 4.0 m/s, relatively low disturbance doesn't have obvious impact on algae but relatively high disturbance has evident inhibition effect on algae. In eutrophic nutrient, disturbance has little effect on the growth rate and the biomass, the specific growth is 0.27-0.29 d(-1). The results show the effect of disturbance on the distribution of nutrients is more important than other factors when the nutrient conditions are quite different in water body. On the condition of nutrient in Lake Taihu, the disturbance doesn't have evident effect on the growth of algae.

Separation and determination of active components in Radix Salviae miltiorrhizae and its medicinal preparations by nonaqueous capillary electrophoresis.

A nonaqueous capillary electrophoresis (NACE) method was developed for simultaneous assay of three bioactive components (1: cryptotanshinone; 2: tanshinone IIA, and 3: tanshinone I) in Radix Salviae miltiorrhizae and in its herbal preparations for the first time. After optimization of separation conditions, a buffer of 250 mmol L(-1) ammonium acetate containing 30% acetonitrile and 1.0% acetic acid (V:V) in methanol was selected for separating the three analytes, but baseline separation of tanshinon I and tanshinone IIA was not obtained. Therefore second-order derivative electropherograms were applied for resolving overlapping peaks. Regression equations revealed good linear relationships (correlation coefficients 0.9943-0.9991) between peak heights in second-order derivative electropherograms and concentrations of the three analytes. The relative standard deviations (RSD) of the migration times and the peak height of the three constituents were in the range of 0.81 -0.88% and 0.34-1.13% (intra-day), 1.57-1.86% and 3.05-5.52% (inter-day), respectively. The recoveries of three constituents ranged from 90.2 to 108.5%. The results indicated that baseline separation of the analytes was sometimes hard to obtain and second-order derivative electropherograms were applicable for the resolving and analysis of overlapping peaks.