An Overview of Traditional Chinese Medicine in the Treatment After Radical Resection of Hepatocellular Carcinoma.

According to the Barcelona Clinic Liver Cancer (BCLC) system, radical resection of early stage primary hepatocellular carcinoma (HCC) mainly includes liver transplantation, surgical resection, and radiofrequency ablation (RFA), which yield 5-year survival rates of about 70-79%, 41.3-69.5%, and 40-70%, respectively. The tumor-free 5-year rate for HCC patients undergoing radical resection only reach up to 13.7 months, so the prevention of recurrence after radical resection of HCC is very important for the prognosis of patients. The traditional Chinese medicine (TCM) takes the approach of multitarget and overall-regulation to treat tumors, it can also independently present the "component-target-pathway" related to a particular disease, and its systematic and holistic characteristics can provide a personalized therapy based on symptoms of the patient by treating the patient as a whole. TCM as postoperative adjuvant therapy after radical resection of HCC in Barcelona Clinic liver cancer A or B stages, and the numerous clinical trials confirmed that the efficacy of TCM in the field of HCC has a significant effect, not only improving the prognosis and quality of life but also enhancing patient survival rate. However, with the characteristics of multi-target, multi-component, and multi-pathway, the specific mechanism of Chinese medicine in the treatment of diseases is still unclear. Because of the positive pharmacological activities of TCM in combating anti-tumors, the mechanism studies of TCM have demonstrated beneficial effects on the regulation of immune function, chronic inflammation, the proliferation and metastasis of liver cancer cells, autophagy, and cell signaling pathways related to liver cancer. Therefore, this article reviews the mechanism of traditional Chinese medicine in reducing the recurrence rate of HCC after radical resection.

Prediction of the mechanisms of action of Qutan Huoxue decoction in non-alcoholic steatohepatitis (NASH): a network pharmacology study and experimental validation.

CONTEXT: Qutan Huoxue decoction (QTHX) is used to treat non-alcoholic steatohepatitis (NASH) with good efficacy in the clinic. However, the mechanism is not clear yet. OBJECTIVE: This study investigates the mechanism of QTHX in the treatment of NASH. MATERIALS AND METHODS: Potential pathways of QTHX were predicted by network pharmacology. Fourty Sprague Dawley (SD) rats (half normal diet, half high-fat diet) were fed six to eight weeks, primary hepatocytes and Kupffer cells were extracted and co-cultured by the 0.4-micron trans well culture system. Then, the normal co-cultured cells were treated by normal serum, the NASH co-cultured cells were treated with various concentrations of QTHX-containing serum (0, 5, 7.5 or 10 µg/mL) for 24 h. The expression of targets were measured with Activity Fluorometric Assay, Western blot and PCR assay. RESULTS: Network pharmacology indicated that liver-protective effect of QTHX was associated with its anti-inflammation response, oxidative stress, and lipid receptor signalling. 10 µg/mL QTHX significantly reduced the inflammation response and lipid levels in primary hepatocytes (ALT: 46.43 ± 2.76 U/L, AST: 13.96 ± 1.08 U/L, TG: 0.25 ± 0.01 mmol/L, TC: 0.14 ± 0.05 mmol/L), comparing with 0 µg/mL NASH group (ALT: 148 ± 9.22 U/L, AST: 53.02 ± 2.30 U/L, TG: 0.74 ± 0.07 mmol/L, TC: 0.91 ± 0.07 mmol/L) (p < 0.01). Meanwhile, QTHX increased expression of SOCS1 and decreased expression of TLR4, Myd88, NF-κB. CONCLUSIONS: The study suggested that QTHX treats NASH in rats by activating the SCOS1/NF-κB/TLR4 pathway, suggesting QTHX could be further developed as a potential liver-protecting agent.

Tanshinone IIA Ameliorates Nonalcoholic Steatohepatitis in Mice by Modulating Neutrophil Extracellular Traps and Hepatocyte Apoptosis.

Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is widely used in the treatment of a variety of diseases and syndromes. Tanshinone IIA (TIIA), a phenanthrenequinone-class derivative extracted from S. miltiorrhiza, is one of its main active components and has anti-inflammatory effects on various tissues and cells. This study aimed to investigate the beneficial effects of TIIA on nonalcoholic steatohepatitis (NASH) induced in mice using a methionine choline deficiency (MCD) diet and the underlying mechanism of these. Our results reveal that TIIA remarkably ameliorated hepatic steatosis and inflammation and decreased the serum levels of liver dysfunction markers while increasing the levels of serum total cholesterol and triglycerides in MCD-fed mice. TIIA significantly reduced mRNA levels of the inflammatory factors TNF-α, IL-6, and TGF-ß. Similarly, TIIA inhibited caspase-3 and Bax-mediated apoptosis in MCD-fed mice. Together, our data indicate that TIIA inhibits the formation of MPO and CitH3 in neutrophil extracellular traps and inhibits apoptosis mediated by caspase-3 and Bax in hepatocytes, thereby mitigating inflammatory progression in an MCD diet-induced NASH mouse model.

Electrochemical aptasensor based on the target-induced strand displacement strategy-driven for T-2 toxin detection.

Herein, an aptasensor based on target-induced strand displacement (TISD) strategy was developed for sensitive detection of T-2 toxin. Gold nanoparticles@ aminated manganese dioxide (AuNPs@NH2-MnO2) exhibited excellent electrical conductivity and provided more binding sites for aptamer (Apt). Besides, polyethyleneimine-reduced graphene oxide/gold­platinum core-shell nanorods composites (PEI-rGO/Pt@Au NRs) were used to be carriers for signaling tags, as their sufficiently large specific surface area improved the loading capacity for signal molecules. In the presence of T-2, the Apt sequence was more inclined to form an Apt-T-2 complex, and the cDNA was displaced from the Apt-cDNA duplex, while the signal tag was released, resulting in a weakened MB signal, differential pulse voltammetry (DPV) was used to record the signal change. Under optimal conditions, the signal response of the constructed electrochemical aptasensor exhibited a good linear relationship with the concentration of T-2. The detection limit was 8.74 × 10-7 ng mL-1over a wide range of concentration from 5 × 10-6 ng mL-1 to 5 ng mL-1. Furthermore, the proposed aptasensor had excellent specificity, good stability and can be well applied to the detection of real samples. It provided a new avenue for the research and development of sensitive aptasensors in food detection and analysis.

Preparation and Characterization of Methyl Jasmonate Microcapsules and Their Preserving Effects on Postharvest Potato Tuber.

Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 µmol L-1 according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation is with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl2. Compared to 300 µmol L-1 MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.

Tanshinone IIA regulates the TGF-ß1/Smad signaling pathway to ameliorate non-alcoholic steatohepatitis-related fibrosis.

Tanshinone IIA (TIIA) is a major component extracted from the traditional herbal medicine Salvia miltiorrhiza and has been indicated to play a role in the treatment of organ fibrosis. However, the evidence supporting its antifibrotic effect is insufficient and the underlying mechanism is unclear. To investigate the therapeutic effect of TIIA on non-alcoholic steatohepatitis-related fibrosis (NASH-F), the present study used a methionine choline deficiency diet to induce NASH-F in rats, and explored the effect of TIIA on the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway. Wistar rats were randomly divided into control, NASH-F and TIIA groups. After 8 weeks of treatment, the levels of serum markers associated with liver function and fibrosis were measured, liver fat vacuoles and inflammation were assessed by haematoxylin and eosin staining, and liver fibrosis was assessed by Masson's trichrome staining. TGF-ß1, Smad2, Smad3, Smad7 and α-smooth muscle actin (α-SMA) mRNA expression, and TGF-ß1, Smad2/3, phosphorylated (p)-Smad2/3, Smad7 and α-SMA protein levels were determined. The results revealed that TIIA could remarkably ameliorate liver fat vacuoles and inflammation in NASH-F rats, and could decrease the levels of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, total bile acid, hyaluronic acid, type Ⅳ collagen, laminin and type III collagen, while increasing the levels of total cholesterol and triglycerides; however, this was not statistically significance. TIIA markedly suppressed the increased TGF-ß1, Smad2, Smad3 and α-SMA mRNA expression levels observed in the liver of NASH-F rats, while it increased the mRNA expression level of Smad7. Similarly, TIIA suppressed the increased TGF-ß1, p-Smad2/3 and α-SMA protein levels observed in the liver of NASH-F rats, while it increased the protein expression level of Smad7 in vitro and in vivo. TIIA had no significant cytotoxic effect at 10, 20, 40 and 80 µmol/l on human LX-2 cell. In conclusion, the findings of the present study indicated that TIIA alleviated NASH-F by regulating the TGF-ß1/Smad signaling pathway. TIIA may be a useful tool in the prevention and treatment of NASH-F.

Tanreqing Injection Regulates Cell Function of Hypoxia-Induced Human Pulmonary Artery Smooth Muscle Cells (HPASMCs) through TRPC1/CX3CL1 Signaling Pathway.

Hypoxia-induced pulmonary arterial hypertension (HPAH) is due to hypoxia caused by vascular endothelial cell remolding and damage. Previous studies have suggested that CX3CL1 plays an important role in HPAH which is affected by oxidative stress. Ca2+ channel activation correlated with increasing NF-κB levels induced by ROS. Tanreqing injection (TRQ) is a traditional Chinese medicine (TCM) for acute upper respiratory tract infection and acute pneumonia. In the present study, we explored the effect of TRQ on human pulmonary artery smooth muscle cells (HPASMCs) undergoing hypoxia and feasible molecular mechanisms involved in. Cell proliferation was assayed using CCK8 kits. Immunofluorescence and western blotting along with ELISA assay were performed to investigate the effect of TRQ on hypoxia-induced ROS, Ca2+, hydroxyl free radicals, and the expression of Ca2+ channel protein TRPC1, CX3CR1, HIF-1α, NF-κBp65, and p-NF-κBp65 in HPASMCs. Human CX3CL1 and the inhibitor of TRPC1 as SKF96365 were used for further investigation. TRQ inhibited hypoxia-induced increasing cell adhesion, ROS, Ca2+, hydroxyl free radicals, CX3CR1, HIF-1α, NF-κBp65 activation, and even on TRPC1 expression in HPASMC which tended to be attenuated even reversed by CX3CL1. Our results suggested that TRQ might help to attenuate remodeling of HPASMC through inhibiting the ROS and TRPC1/CX3CL1 signaling pathway.

Clinical efficacy of Shugan granule in the treatment of mixed anxiety-depressive disorder: A multicenter, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Shugan granule is derived from Xiaoyao powder, a traditional Chinese medicine that has been shown to be effective in treating emotional disorders. At present, there is no standard drug treatment for mixed anxiety-depressive disorder (MADD), and no evidence-based clinical trial has been performed for any drug, meaning MADD patients are unable to obtain standardized treatment. AIM OF THE STUDY: The purpose of this clinical trial was to test the clinical efficacy and safety of Shugan granules in the treatment of MADD, and to provide clinical trial-based support along with drug recommendations for the treatment of MADD. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled study was conducted on 400 patients with MADD recruited from January 1, 2019 to December 31, 2020, and they were randomly divided into test and placebo groups with a 1:1 ratio. Subjects in the test group (n = 200) received oral administration of Shugan granules, while subjects in the placebo group (n = 200) received oral administration of a Shugan granule simulator. The treatment lasted for 8 weeks. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression Scale (CGIS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used to evaluate efficacy. In addition, the traditional Chinese medicine (TCM) syndrome scale for MADD was developed to observe improvements of related symptoms in patients after treatment based on the disease guidelines of TCM and the clinical manifestations of depression. Furthermore, the safety of Shugan granules was evaluated during and after treatment. RESULTS: After 8 weeks of treatment, the total scores for HAMA, HAMD, SAS, and SDS in the test group were significantly lower than those in the placebo group (P < 0.01). The proportion of patients with efficacy index (EI) > 1 for the CGIS score in the test group was significantly higher than that in the placebo group (P < 0.01). The efficacy of treatment in the test group based on the TCM syndrome scale was 70.16% and 88.27% after 4 weeks and 8 weeks, respectively, which was significantly higher than that in the placebo group (44.27% and 66.67% after 4 weeks and 8 weeks, respectively; P < 0.01). The disappearance rate of single symptoms in the test group was 20-30% higher than that in the placebo group, with a significant difference between groups (P < 0.05). During the treatment period, the incidence of adverse reactions was 2.05% in the test group and 2.06% in the placebo group, with no significant differences noted (P = 1.0000). CONCLUSION: Shugan granule was more effective than placebo in the treatment of MADD. Moreover, there was no significant difference between the two groups in terms of safety. This paper provides a clinical therapeutic regime using Shugan granule for the treatment of MADD.

Effects of Qutan Huoxue Formula on the SOCS1/TLR4 Signaling Pathway in NASH Model Mice.

The purpose of this study was to investigate the effects of Qutan Huoxue Formula (QHF) on liver injury in mice with nonalcoholic steatohepatitis (NASH) by upregulating SOCS1 to inhibit the TLR4/NF-κB signaling pathway. Thirty male C57BL/6J mice (20-22 g) were randomly divided into the normal diet group (ND group), methionine- and choline-deficient diet group (MCD group), and Qutan Huoxue Formula group (QHF group). Mice in the ND group were fed a regular diet, while mice in other two groups were fed MCD diet. After successful molding, the QHF group was gavaged by QHF. The ND group and MCD group were gavaged by the same volume of normal saline, once a day. During the period of gavaging, all mice continue to be fed MCD fodder except for the ND group. All mice were killed at 8 w. H&E staining and Oil Red O staining were used to observe the pathological changes of liver tissues. Serum level of ALT, AST, TC, and TG was detected by enzyme-linked immunosorbent assay. The expression of liver SOCS1, TLR4, Myd88, and NF-κB was detected by real-time PCR, immunohistochemistry, and Western blot. QHF can significantly reduce the serum levels of ALT, AST, TC, and TG of NASH mice and reduce the degree of liver fat degeneration and inflammation. It also can decrease both mRNA and protein expressions of liver TLR4, Myd88, and NF-κB. The mRNA expression of SOCS1 increased, while the SOCS1 protein expression decreased. In conclusion, QHF can significantly alleviate hepatic steatosis and inflammation in NASH mice by upregulating SOCS1 to inhibit the TLR4/NF-κB signaling pathway.

Effects of Xingnaojing on serum high-sensitivity C-reactive protein and neuron-specific enolase in patients with acute cerebral hemorrhage: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will systematically explore the effects of Xingnaojing (XNJ) on serum high-sensitivity C-reactive protein (hs-CRP) and neuron-specific enolase (NSE) in patients with acute cerebral hemorrhage (ACH). METHODS: We will comprehensively search the following electronic databases (MEDLINE, EMBASE, Cochrane Library, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure) from inception to the March 1, 2020. There are no limitations related to the language and publication status. Two authors will independently perform all citation identification, information extraction, and study quality. All potential conflicts will be solved through discussion with the help of a third author. RevMan 5.3 software will be used for data synthesis and statistical analysis. RESULTS: This study will summarize the present evidence to investigate the effects of XNJ on serum hs-CRP and NSE in patients with ACH. CONCLUSION: This study may provide an impressive understanding of perspective from scientific basis for effects of XNJ on serum hs-CRP and NSE in patients with ACH. STUDY REGISTRATION: PROSPERO CRD42020171648.

Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model.

Though succinate accumulation is associated with reactive oxygen species (ROS) production and neuronal injury, which play critical roles in epilepsy, it is unclear whether succinate accumulation contributes to the onset of epilepsy or seizures. We sought to investigate changes in succinate, oxidative stress, and mito-SOX levels, as well as mitophagy and neuronal change, in different status epilepticus (SE) rat models. Our results demonstrate that KA-induced SE was accompanied by increased levels of succinate, oxidative stress, and mito-SOX, as well as mitophagy and neuronal degeneration. The similarly increased levels of succinate, oxidative stress, and mito-SOX were also found in pilocarpine-induced SE. Moreover, the reduction of succinate accumulation by the inhibition of succinate dehydrogenase (SDH), malate/aspartate shuttle (MAS), or purine nucleotide cycle (PNC) served to reduce succinate, oxidative stress, and mito-SOX levels, thereby preventing oxidative stress-related neuronal damage and lessening seizure severity. Interestingly, simulating succinate accumulation with succinic acid dimethyl ester may induce succinate accumulation and increased oxidative stress and mito-SOX levels, as well as behavior and seizures in electroencephalograms similar to those observed in rats exposed to KA. Our results indicate that succinate accumulation may contribute to the increased oxidative stress/mitochondrial ROS levels, neuronal degeneration, and SE induced by KA administration. Furthermore, we found that succinate accumulation was mainly due to the inverse catalysis of SDH from fumarate, which was supplemented by the MAS and PNC pathways. These results reveal new insights into the mechanisms underlying SE and that reducing succinate accumulation may be a clinically useful therapeutic target in SE.

Characterization of aerobic granular sludge of different sizes for nitrogen and phosphorus removal.

Granular size plays a key role in the performance of the aerobic granular sludge (AGS). As the diameter of the granule increases, stratification may begin to appear due to the increase in mass transfer resistance. Aerobic granules harvested from a lab-scale anaerobic-aerobic sequencing batch reactor (AO-SBR) were classified into three categories according to their size: (a) 0.15-0.28 mm, (b) 0.28-0.45 mm and (c) larger than 0.45 mm. In this study, the categories were called small-size, medium-size and large-size granules, respectively. A fraction of the different forms of phosphate and denitrification efficiency was investigated in each category. Results show that small-size granules present much more easily mobile phosphorus than other granules. Moreover, the denitrification performance has been tested by using dumping and trickling patterns for COD and NO3--N feeding. The results demonstrated that the large-size granules exhibit poor denitrification rates, as opposed to the medium-size granules. Therefore, medium-size granules, with a size of 0.28-0.45 mm, are regarded as the most suitable granular size for AGS in this experiment from the perspective of denitrification and phosphorus removal.

[Physicochemical characteristics of granules with different size in a granular sludge system for phosphorus removal].

Aerobic granular sludge that could simultaneously remove nitrogen and phosphorus was cultivated in a sequencing batch reactor (SBR). Three groups were divided using 100-, 60- and 40- mesh sieves resulting the size ranges were 150-280 microm, 280-450 microm and > 450 microm, respectively, and the physicochemical properties of different groups were analyzed. Results showed that during the initial period of granulation (7 - 18 d), the compact granules could provide the anaerobic niche for the substrate the competition between GAOs and PAOs; and the compact granules was favorable for the enrichment and growth of PAOs, resulting in different phosphorous fractions in different size of granules: granules with the size of 280 - 450 microm exhibited the highest content of organic phosphorous faction, i.e., 113.25 mg x g(-1). In contrast, these granules showed the lowest content of inorganic phosphorous fraction, i.e., 15.55 mg x g(-1). In a later period, the content of organic phosphorous fraction in granules was similar after 34 d about 50 mg x g(-1), and the inorganic phosphorous fraction became similar after 52 d was 70 mg x g(-1), and the total organic phosphorous fraction of sludge in the reactor were higher than those in the solids effluent. The phosphorous fraction in different size granules was affected by the sludge retention time. The total phosphorous accounted for 11% of total weight of sludge, and the inorganic phosphorous accounted 4.24%. Additionally, the settling velocity, specific weight of bigger granules were higher than the smaller one, and these values were well correlated with total phosphorous. Concerning on denitrification, bigger and smaller granules showed high denitrification efficiency, and the gradient of NO3(-) -N between inside of granules and bulk solution was an important factor for denitrification rate.