Aspercitrininone A, novel antibacterial polyketide featuring unusual spiral skeleton from Aspergillus cristatus.

Aspercitrininone A (1), a novel polyketide featuring an unprecedented tetracyclic 6/6/6/5 spiral skeleton, was obtained from the rice fermentation cultures of the fungus Aspergillus cristatus together with five known compounds (2-6). Their structures were determined by HRESIMS data, 1D and 2D NMR spectroscopic analysis, and electronic circular dichroism (ECD) calculations. Aspercitrininone A was revealed as a new type of C/D cycle spiral structure and an unusual addition product of o-quinoid form citrinin with 2-methylterrefuranone. Compounds 1, 4, and 5 exhibited potent antibacterial activities with minimal inhibitory concentration (MIC) values from 13.2 to 67.3 µg/mL against four strains of human pathogenic bacteria in vitro.

Metabolomics analysis of the nutraceutical diversity and physiological quality of Torreya yunnanensis seeds during cold storage.

This study investigated how cold storage affects the nutraceutical diversity and physiological quality of Torreya yunnanensis seeds, using a widely targeted UPLC-MS/MS-based metabolomics analysis. The 373 identified metabolites were divided into nine categories: lipids, phenolic acids, amino acids and derivatives, organic acids, nucleotides, saccharides, vitamins and alcohols. Among them, 49 metabolites showed significant changes after 3 months of cold storage, affecting 28 metabolic pathways. The content of amino acid-related metabolites significantly increased, while the content of sugar-related metabolites decreased during storage. Notably, the content of proline acid, shikimic acid, α-linolenic acid and branched-chain amino acids showed significant changes, indicating their potential role in seed storage. This study deepens our understanding of the nutraceutical diversity and physiological quality of T. yunnanensis seeds during storage, providing insight for conservation efforts and habitat restoration.

The anti-allergic potential of stingless bee honey from different botanical sources via modulation of mast cell degranulation.

BACKGROUND: Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells. METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and ß-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods. RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers. CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase.

OBJECTIVE: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. METHODS: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg-1•d-1), MPA + low-dose (20 mg•kg-1•d-1) JP (L-JP), MPA + medium-dose (30 mg•kg-1•d-1) JP (M-JP), and MPA + high-dose (40 mg•kg-1•d-1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. RESULTS: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. CONCLUSIONS: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).

Chitooligosaccharide-catechin conjugate loaded liposome using different stabilising agents: characteristics, stability, and bioactivities.

AIM: To determine the optimum condition for preparing chitooligosaccharide-catechin conjugate (COS-CAT) liposomes using different stabilising agents. METHODS: COS-CAT liposomes (0.1-1%, w/v) were prepared using soy phosphatidylcholine (SPC) (50-200 mM) and glycerol or cholesterol (25-100 mg). Encapsulation efficiency (EE), loading capacity (LC), physicochemical characteristics, FTIR spectra, thermal stability, and structure of COS-CAT liposomes were assessed. RESULTS: COS-CAT loaded liposome stabilised by cholesterol (COS-CAT-CHO) showed higher stability as shown by the highest EE (76.81%) and LC (4.57%) and the lowest zeta potential (ZP) (-76.51 mV), polydispersity index (PDI) (0.2674) and releasing efficiency (RE) (53.54%) (p < 0.05). COS-CAT-CHO showed the highest retention and relative remaining bioactivities of COS-CAT under various conditions (p < 0.05). FTIR spectra revealed the interaction between the choline group of SPC and -OH groups of COS-CAT. Phase transition temperature of COS-CAT-CHO was shifted to 184 °C, which was higher than others (p < 0.05). CONCLUSION: SPC and cholesterol-based liposome could be used as a promising vesicle for maintaining bioactivities of COS-CAT.

Ethanolic Extract of Duea Ching Fruit: Extraction, Characterization and Its Effect on the Properties and Storage Stability of Sardine Surimi Gel.

The quality of surimi gel can be improved using protein cross-linkers, especially from plant extracts. Apart from the presence of phenolic compounds, Duea ching fruit is rich in calcium, which can activate indigenous transglutaminase or form the salt bridge between protein chains. Its extract can serve as a potential additive for surimi. The effect of different media for the extraction of Duea ching was studied and the use of the extract in sardine surimi gel was also investigated. The Duea ching fruit extract (DCE) was prepared using distilled water and ethanol (EtOH) at varying concentrations. The DCE prepared using 60% EtOH (DCE-60) had the highest antioxidant activity and total phenolic content. When DCE-60 (0-0.125%; w/w) was added to the sardine surimi gel, the breaking force (BF), deformation (DF) and water holding capacity (WHC) of the gel upsurged and the highest values were attained with the 0.05% DCE-60 addition (p < 0.05). However, the whiteness of the gel decreased when DCE-60 levels were augmented. The gel containing 0.05% DCE-60, namely D60-0.05, showed a denser network and had a higher overall likeness score than the control. When the D60-0.05 gel was packed in air, under vacuum or modified atmospheric packaging and stored at 4 °C, BF, DF, WHC and whiteness gradually decreased throughout 12 days of storage. However, the D60-0.05 gel sample showed lower deterioration than the control, regardless of the packaging. Moreover, the gel packaged under vacuum conditions showed the lowest reduction in properties throughout the storage than those packaged with another two conditions. Thus, the incorporation of 0.05% DCE-60 could improve the properties of sardine surimi gel and the deterioration of the resulting gel was retarded when stored at 4 °C under vacuum packaging conditions.

Ophiopogon japonicus and its active compounds: A review of potential anticancer effects and underlying mechanisms.

BACKGROUND: Ophiopogon japonicus (Thunb.) Ker Gawl., a well-known Chinese herb, has been used in traditional Chinese medicine for thousands of years. Extensive in vitro and in vivo studies have shown that O. japonicus and its active compounds exhibit potential anticancer effects in a variety of cancer cells in vitro and suppress tumor growth and metastasis without causing serious toxicity in vivo. PURPOSE: This review aims to systemically summarize and discuss the anticancer effects and the underlying mechanisms of O. japonicus extracts and its active compounds. METHODS: The review is prepared following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Various scientific databases including Web of Science, PubMed, Scopus, and Chinese National Knowledge Infrastructure were searched using the keywords: Ophiopogon japonicus, tumor, cancer, carcinoma, content, pharmacokinetics, and toxicity. RESULTS: O. japonicus extracts and the active compounds, such as ruscogenin-1-O-[ß-d-glucopyranosyl(1→2)][ß-d-xylopyranosyl(1→3)]-ß-d-fucopyranoside (DT-13), ophiopogonin B, and ophiopogonin D, exert potential anticancer effects, including the induction of cell cycle arrest, activation of apoptosis and autophagy, and inhibition of metastasis and angiogenesis. In addition, the mechanisms underlying these effects, as well as the pharmacokinetics, toxicity and clinical utility of O. japonicus extracts and active compounds are discussed. Furthermore, this review highlights the research and application prospects of these compounds in immunotherapy and combination chemotherapy. CONCLUSIONS: The traditional herb O. japonicus and its phytochemicals could be safe and reliable anticancer drug candidates, alone or in combination with chemotherapeutic drugs. We hope that this review, which highlights the anticancer properties of O. japonicus, will contribute to drug optimization, therapeutic development, and future studies on cancer therapies based on this medicinal plant.

Green Carbon Dots: Synthesis, Characterization, Properties and Biomedical Applications.

Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, "zero-dimensional" carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.

Novel intelligent films containing anthocyanin and phycocyanin for nondestructively tracing fish spoilage.

Potential pH-responsive films were developed based on incorporating anthocyanin, phycocyanin, and a mixture of anthocyanin-phycocyanin (at a ratio of 3:1 v/v) within composite gelatin (1.5 g / 100 g film solution)/soybean polysaccharide (2.5 g / 100 g film solution) matrices. FTIR and SEM assessments certified the incorporation of the pigments into the film matrices. All the colorimetric films were highly sensitive when exposed to headspace ammonia, except the phycocyanin-incorporated film. Moreover, the fabricated intelligent films were conducted to trace the spoilage process of grass carp. An obvious relationship between the color (L*, a*, b*, ΔE) of indicators and pH, TVB-N, bacterial growth, ATP-related compounds, and K-value of the fish was observed. The film incorporated with mixed Ipomoea nil extract and phycocyanin possessed the best color variations (dark orange, pink, dark blue) with the degree of fish spoilage. Therefore, this intelligent film can be considered a promising sensor for monitoring fish freshness non-destructively.

Cell metabolomics study on the anticancer effects of Ophiopogon japonicus against lung cancer cells using UHPLC/Q-TOF-MS analysis.

Ophiopogon japonicus (OJ) is a traditional Chinese herbal medicine that has been used for thousands of years. Recently, the anticancer effects of OJ have been reported in multiple types of cancer, particularly in lung cancer. However, the underlying mechanisms remain unclear. In present study, the effects of OJ against NCI-H1299 human lung cancer cells were investigated, and the underlying mechanisms were explored using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS)-based cell metabolomics. As a result, OJ inhibited the proliferation, induced the apoptosis and suppressed the migration of NCI-H1299 cells. A total of 22 differential metabolites responsible for the effects of OJ were screened and annotated based on the LC-MS-based cell metabolomics approach. The altered metabolites were involved in three metabolic pathways, including glycerophospholipid metabolism, ether lipid metabolism and glutathione metabolism. These results showed that cell metabolomics-based strategies are promising tools to discover the action mechanisms of OJ against lung cancer cells.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Micro-CT and SEM investigation of sound absorption structure and chambers in the otoliths of Giant Panda fish species - Chinese Bahaba (Bahaba taipingensis).

As a critically endangered (CR) fish species, Chinese Bahaba is a unique "Giant Panda" fish species in China and has been listed among the national first-class wildlife protection animals and China's top 10 genetic resources of aquatic products since 2021. This fish species is of high commercial value because its swim bladder is commonly used in traditional Chinese medicine. Its otoliths are the sensory organs immersed in the endolymph for maintaining its balance and hearing. However, rare information has been reported on the sound absorption structure and chambers of otoliths of such "Giant Panda" fish. The big "C" groove was found in the fish's front sagittal otolith with the crystal cluster in the back sagittal otolith, the former of which is a 3D layered structure, that is constructed by elongated prismatic crystals. Besides, there are numerous small holes and adhesion material in this 3D layered structure, where many chambers were also found, indicating that some specific sounds may be captured by this structure and these chambers may then amplify such sounds at a certain wavelength. This finding could be of great importance for protecting and conserving this critically endangered species.

Chemical Comparison of Monk Fruit Products Processed by Different Drying Methods Using High-Performance Thin-Layer Chromatography Combined With Chemometric Analysis.

Monk fruit, also named Luo Han Guo, is the fruit of Siraitia grosvenorii (Swingle) C. Jeffrey ex A. M. Lu et Z. Y. Zhang and has been used as both food and traditional Chinese medicine. Due to preservation concerns, monk fruit is usually processed by hot-air drying or using low-temperature techniques after harvest. In this study, high-performance thin-layer chromatography (HPTLC) method was developed for the analysis of 13 mogrosides, 1 flavonoid, and 3 sugars in monk fruit products. Then chemometric analysis was applied to investigate the chemical characteristics in the samples dried by different methods. The results showed that the contents of mogroside V, 11-oxo-mogroside V, isomogroside V, and sucrose in monk fruits dried at low temperature were much higher than those in traditional hot-air drying samples, which was also confirmed by HPTLC-scanning. These findings indicate that HPTLC combined with chemometric analysis provides a reliable tool to understand the chemical differences between the monk fruit products processed by different drying methods, which will be helpful for their quality evaluation.

Efficacy of freeze-chilled storage combined with tea polyphenol for controlling melanosis, quality deterioration, and spoilage bacterial growth of Pacific white shrimp (Litopenaeus vannamei).

This study aimed to investigate melanosis, quality attributes, and bacterial growth of freeze-chilled Pacific white shrimp (Litopenaeus vannamei) during 6 days of chilled storage, as well as the preservative effects of tea polyphenol on shrimp. The results showed that freeze-chilled storage retarded the growth of bacteria and the accumulation of putrescine in shrimp. The growth of spoilage bacteria Photobacterium and Shewanella were inhibited. However, freeze-chilled storage aggravated melanosis and lipid oxidation. The total volatile basic nitrogen (TVB-N) slightly accumulated in the thawed shrimp. The incorporation of tea polyphenol preserved freeze-chilled shrimp. Melanosis and lipid oxidation of shrimp were alleviated. The accumulation of biogenic amines, TVB-N, hypoxanthine riboside, and hypoxanthine were retarded. Meanwhile, the growth of spoilage bacteria Pseudoalteromonas, Photobacterium, Psychrobacter, and Carnobacterium were inhibited. Based on sensory analysis, the shelf-life of chilled, freeze-chilled, and freeze-chilled tea polyphenol shrimp were 4 days, 3 days, and 6 days, respectively.

Ablation Therapy Combined with EGFR TKIs in the Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3. RESULTS: A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: -2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: -2.80, 95% CI: 1.64 to 4.80, P< 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: -1.66, 95% CI: 1.20 to 2.31, P< 0.01), and disease control rate (DCR) (RR: -2.68, 95% CI: 1.41 to 5.06, P< 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone. CONCLUSION: Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.

[Analysis and considerations on revision of instructions for traditional Chinese medicine injections].

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

High-continuity genome assembly of the jellyfish Chrysaora quinquecirrha.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

Analysis and considerations on revision of instructions for traditional Chinese medicine injections / 中国中药杂志

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

[Traditional Chinese medicine for ulcerative colitis: systematic reviews based on PRIO-harms].

This article is aimed to reevaluate the systematic reviews(Meta-analysis) of traditional Chinese medicine in the treatment of ulcerative colitis, and provide reference for evidence-based decision-making of traditional Chinese medicine(TCM). According to the preferred reporting items for overviews(preferred reporting items for overview of systematic reviews, PRIO-harms), the main Chinese and English electronic literature databases(PubMed, Cochrane Library, EMbase, CNKI, CBM, etc.) were retrieved, supplemented by manual retrieval. Systematic reviews for the treatment of ulcerative colitis with Chinese medicine up to February 2019 were included. Two researchers independently performed literature screening and data extraction. The methodology quality, reporting quality and evidence quality of the literature were evaluated by AMSTAR 2 tool, PRISMA scale and GRADE system respectively. Subgroup analysis was performed by using RevMan 5.3 software. A total of 21 systematic reviews were included, and the interventions mainly included TCM internal and external treatment, with 53 outcome indicators. The AMSTAR 2 results showed that 5 articles were of high quality, 9 of medium quality, 4 of low quality, and 3 of extremely low quality. The most problematic items were as follows: the list of excluded documents was not provided; the sources of funding for each study were not reported; and the research methods were not determined before implementation. PRISMA scale had an average score of(20.38±1.43) points, less than 22 points for 15 articles, with certain reporting defects. The GRADE system suggested that the quality of the evidence for the 30 outcome indicators was low or very low. The most important factors leading to degrading was the limitation, followed by publication bias and inconsistency. The results showed that as compared with conventional Western medicine, TCM oral or enema treatment for mild to moderate ulcerative colitis had better clinical efficacy and safety. Due to the quality limitations of the included studies, it is necessary to further strengthen the top-level design and follow the scientific research paradigm to provide a higher level of evidence for the clinical evidence-based decision-making of TCM.

Correlation Analysis of " Toxin Damaging Brain Collaterals" from Glymphatic System / 中国实验方剂学杂志

The collaterals are branches of the meridians and vessels system, and have the roles of connecting upper-lower and interior-exterior portions of the body, the characteristics of two-way flow in supporting the operation of Qi and blood, and the functions of material exchange and metabolism. The brain is the intersection of the Yang meridians. Crisscross brain collaterals permeate Qi and blood to enrich the brain, and spread Yang Qi, in order to warm the brain-mind, and provide material basis and source power to the " brain governing mind" . Under pathological conditions, cerebral collaterals are blocked, and toxic pathogens are endogenous, resulting in " toxin damaging brain collaterals" . This theory is not only applied to the study of stroke pathogenesis, but also extended to other encephalopathy, such as dementia, which promoted the development of the theory of pathogenesis in traditional Chinese medicine. Recently, a " glymphatic system" was discovered in the brain, which is an exchange flow system of cerebrospinal fluid-brain interstitial fluid mediated by astrocyte. The glymphatic system transports nutrients and neuroactive substances, such as glucose, lipids, electrolytes and apolipoprotein E in the cerebrospinal fluid, to brain tissue, and also removes metabolic products (such as lactic acid), soluble proteins (such as β-amyloid protein and Tau protein) from the brain and foreign bodies, which are important liquid flow systems that maintain the homeostasis of the brain. The discovery of the glymphatic system provides a new perspective for the study of pathological mechanism of neurological diseases, and may become a new target for interventions in neurological diseases, such as cerebrovascular diseases and neurodegenerative diseases. As a widely distributed cerebral metabolic waste removal way and material delivery system, the lymphatic system may be the biological foundation of " brain collateral" disease, and a cross point of understanding on " toxin impairing brain collaterals" by Western and traditional Chinese medicine. The study based on the glymphatic system will give a more rational explanation on " toxic damage to brain collaterals" .