Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

[Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer].

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

[Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer].

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

Being beneficial to self and caregiver: the role of dispositional mindfulness among breast cancer patients.

PURPOSE: Breast cancer (BC) patients report complex negative emotions, including symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD). What's more, being diagnosed with cancer also has a negative impact on the patient's family such as additional financial burden and care needs, leading to higher levels of caregiver burden. This study aimed to explore whether dispositional mindfulness could alleviate multiple negative emotions of BC patients and to investigate the mediating effect of caregiver burden on the relationship between the patients' dispositional mindfulness and negative emotions. METHODS: A sample of 230 Chinese BC patients receiving chemotherapy and their caregivers voluntarily participated in the study by completing a set of questionnaires including the Mindfulness Attention Awareness Scale, the Caregiver Self-assessment Questionnaires, the General Anxiety Symptoms Scale, the Patient Health Questionnaire, and the PTSD Symptom Scale. Structural equation modeling was used to test the relationship between dispositional mindfulness, negative emotions, and caregiver burden. RESULTS: Dispositional mindfulness was significantly and negatively correlated with negative emotions, including anxiety, depression, and PTSD among the BC patients. Structural equation modeling showed that caregiver burden mediated the relation between patients' dispositional mindfulness and negative emotions. CONCLUSION: BC patients with higher levels of dispositional mindfulness showed less negative emotions. The results of the mediation analysis suggested that higher levels of dispositional mindfulness of breast cancer patients could decrease the caregivers' perceived burden and, in turn, relieve patients' negative emotions. Dispositional mindfulness was beneficial to breast cancer patients as well as their caregivers, indicating that mindfulness-based interventions targeting distress in patient-caregiver dyads would be more effective than what interventions for patients alone.

Insight into nitrogen and phosphorus enrichment on cadmium phytoextraction of hydroponically grown Salix matsudana Koidz cuttings.

Cadmium (Cd) has already caused worldwide concern because of its high biotoxicity to human and plants. This study investigated how nitrogen (N) and phosphorus (P) enrichment alter the toxic morpho-physiological impacts of and accumulation of Cd in hydroponically grown Salix matsudana Koidz cuttings. Our results showed that Cd significantly depressed growth and induced a physiological response on S. matsudana cuttings, exhibiting by reduced biomass, decreased photosynthetic pigment concentrations, and increased soluble protein and peroxidase activity of shoots and roots. N and P enrichment alleviated the Cd toxic effects by increasing production of proline which prevented cuttings from damage by Cd-induced ROS, displaying with decreased malondialdehyde concentration, and stimulated overall Cd accumulation. Enrichment of N and P significantly decreased the upward Cd transfer, combing with enhanced root uptake (stimulated root activity) and retranslocation from stem, resulted in extensive Cd sequestration in S. matsudana roots. In both root and xylem, concentration of Cd is positively correlated with N and P. The improved phytoextraction potential by N and P enrichment was mainly via elevating Cd concentration in roots, probably by increased production of phytochelatins (e.g., proline) which form Cd chelates and help preventing damage from Cd-induced ROS. This study provides support for the application of S. matsudana in Cd phytoextraction even in eutrophic aquatic environments.

Numerical assessment of the environmental impacts of deep sea cage culture in the Yellow Sea, China.

In light of environmental deterioration in coastal areas, deep sea cage aquaculture is becoming an increasingly attractive mode of mariculture. A key factor in determining the potential of deep sea cage aquaculture is to evaluate the environmental impacts of these practices. Here, a numerical model consisting of coupled hydrodynamic-, tracer-tracking- and 3-D Lagrangian particle-tracking models was set up and applied to evaluate the environmental impacts of deep sea cage cultivation of sea bass (Lateolabrax japonicus) in the Yellow Sea, China. The model was verified using water level data on August 1-31, 2018 and nutrient concentration in water and surface sediments in May, August, and November 2018, and January 2019. Results show that the model successfully captures the characteristics of local tidal currents and the total particulate nitrogen and phosphorus concentrations of the underlying sediments. Water quality simulations indicate that deep sea cages account for 26% of the total dissolved inorganic nitrogen and 19% of the active phosphorus content. Residual feed particles are predicted to fall in an ellipse centered on the cage location, with a long axis of 200 m and a short axis of 50 m. Feces are predicted to fall in an ellipse with a long axis of 1400 m and a short axis of 600 m. The Superposition particles are predicted to settle in an ellipse with a long axis of 320 m and a short axis of 150 m. The model results indicate that installation of all deep sea cages will lead to acceptable levels of water quality, but that sediments may become polluted. The coupled model can be used to predict the environmental impacts of deep sea cage farming and provide a useful tool for designing the layout of integrated multi-trophic aquaculture of organic extractive or inorganic extractive species.

Neuronal Signal Transduction-Involved Genes in Pig Hypothalamus Affect Feed Efficiency as Revealed by Transcriptome Analysis.

Feed efficiency (FE) is an important trait affecting costs in swine industry. Investigation on FE-related genes in different tissues is valuable for molecular breeding. Hypothalamus is a convergent and integrated centre for multiple nutrient-related signals. The present study identified 363 differentially expressed (DE) genes and 14 DE lincRNAs in the hypothalamus of high- and low-FE Yorkshire pigs. Furthermore, 983 significantly correlated DE gene-lincRNA pairs were identified through weighted correlation network analysis (WGCNA) and Pearson correlation analysis. These DE genes were primarily enriched in the neuronal signal transduction process containing the upregulated genes of VIPR1, CCR1, CCR5, LEPR, INSR, ADRA1A, CCKAR, and ADORA3 and the downregulated genes of GRM1, GRM4, GRM5, and VIPR2, which were located in the cell membrane. These signal receptors were mainly connected to downstream Jak-STAT signaling that involved the increased genes (JAK2, STAT3, and POMC) and mTOR signaling pathway, including the decreased genes (CAMKK2, AMPK, and MTOR). STAT3 and AMPK genes also played a role in two major hypothalamic neurons of POMC and NPY/AGRP. A total of eight DE lincRNAs also participated in the potential network. In conclusion, neuronal signaling transduction-involved genes and lincRNAs were related to FE variation in pig hypothalamus.