Comparative Investigations on Properties of Three Kinds of FDM 3D-Printed Natural Plant Powder/Poly(lactic acid) Biocomposites.

In order to further explore the feasibility of the application of the residue of Chinese herbal medicine in FDM 3D technology and enrich the kinds of printing materials, Astragalus residue powder(ARP)/poly(lactic acid) (PLA) biocomposite was FDM 3D-printed, meanwhile, two traditional biocomposites, i.e., wood flour (WF)/PLA and rice straw powder (RSP)/PLA, were prepared by the same method, and the properties of the biocomposites were comparatively investigated. The results showed that, the tensile and flexural strengths of ARP/PLA were 28.33 MPa and 97.60 MPa, respectively, which were 2.85% and 10.89% smaller than those of WF/PLA, while 15.73% and 7.04% greater than those of RSP/PLA. WF/PLA showed typical brittle fracture characteristics, ARP/PLA and RSP/PLA both showed ductile fracture, but not obviously. Among the three kinds of biocomposites, ARP/PLA was the most thermally stable, followed by WF/PLA and RSP/PLA in turn. The incorporation of natural plant powder had no significant effect on the glassy transition, melting, and cold-crystallization behaviors of PLA, but the crystallinity of PLA could be increased from 0.3% to 2.0% and 1.9%, respectively, by adding ARP and WF. At 20 °C, the storage modulus of ARP/PLA, WF/PLA and RSP/PLA was 2759.4 MPa, 3361.3 MPa, and 2691.5 MPa, respectively, indicating that WF/PLA has the greatest stiffness, and the stiffness of RSP/PLA was the least. In addition to these, all the biocomposites were hydrophilic, the contact angle of the distilled water on the surface of ARP/PLA, WF/PLA or RSP/PLA was correspondingly 73.5°, 77.6° and 71.2°. Overall, it can be concluded that ARP/PLA has moderate strengths, stiffness and wettability, meanwhile, it is the most thermal stable among the three biocomposites, and can be processed at a temperature close to that of PLA. ARP/PLA is suitable as a new kind of feedstock material for FDM 3D printing.

[Screening methods of traditional Chinese medicine for coronary heart disease and angina pectoris: an exploration based on core outcome set and fuzzy comprehensive evaluation].

It was pointed out in Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine issued by the State Council in 2019 that 100 varieties of traditional Chinese medicine(TCM) with unique curative effects should be screened out within about three years. Due to the multi-component and multi-target mechanisms of TCM varieties, it is difficult to directly and simply evaluate their multi-dimensional clinical value using methods applicable to chemical or biological agents. The heterogeneity of outcomes for similar TCM makes it difficult to determine the advantages of similar products. The fuzzy comprehensive evaluation method that is developed on the basis of core outcome set and fuzzy mathematics for clinical efficacy evaluation of TCM may solve these problems. This study developed a fuzzy comprehensive evaluation model for the clinical efficacy evaluation of Chinese patent me-dicines for coronary heart disease and angina pectoris, and selected the previous normative studies with complete or incomplete data for verifying the model application. The results showed that original studies with complete data failed to evaluate and compare the comprehensive efficacy of different interventions. The original research only mentioned the advantages and disadvantages of different interventions in different aspects. The comprehensive clinical efficacy of three different interventions obtained through fuzzy comprehensive evaluation was all graded as level Ⅱ. The original research with incomplete data drew the same conclusions as the fuzzy comprehensive evaluation, and the results of fuzzy comprehensive evaluation can provide more comprehensive information. Therefore, the fuzzy comprehensive evaluation shows the products with overall advantages of clinical efficacy, which may become a feasible method for the screening of TCM.

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine.

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

1,10-Seco-Eudesmane sesquiterpenoids as a new type of anti-neuroinflammatory agents by suppressing TLR4/NF-κB/MAPK pathways.

Dysregulation of neuroinflammation is a key pathological factor in the progressive neuronal damage of neurodegenerative diseases. An in-house natural products library of 1407 compounds were screened against neuroinflammation in lipopolysaccharide (LPS)-activated microglia cells to identify a novel hit 1,6-O,O-diacetylbritannilactone (OABL) with anti-neuroinflammatory activity. Furthermore, a 1,10-seco-eudesmane sesquiterpenoid library containing 33 compounds was constructed by semisynthesis of a major component 1-O-acetylbritannilactone (ABL) from the traditional Chinese medicinal herb Inula Britannica L. Compound 15 was identified as a promising anti-neuroinflammatory agent by nitrite oxide (NO) production screening. 15 could attenuate tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) productions, and inhibit the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at a submicromolar level. Mechanistic study revealed that 15 significantly modulated TLR4/NF-kB and p38 MAPK pathways, and upregulated the anti-oxidant response HO-1. Besides, 15 promoted the conversion of the microglia from M1 to M2 phenotype by increasing levels of arginase-1 and IL-10. The structure-activity relationships (SARs) analysis indicated that the α-methylene-γ-lactone motifs, epoxidation of C5=C10 bond and bromination of C14 were important to the activity. Parallel artificial membrane permeation assay (PAMPA) also demonstrated that 15 and OABL can overcome the blood-brain barrier (BBB). In all, compound 15 is a promising anti-neuroinflammatory lead with potent anti-inflammatory effects via the blockage of TLR4/NF-κB/MAPK pathways, favorable BBB penetration property, and low cytotoxicity.

[Effect of icaritin on proliferation and apoptosis of human ovarian cancer cells SKOV3].

Based on the PI3K/Akt signaling pathway, this study aimed to observe the proliferation and apoptosis of ovarian cancer SKOV3 cells at different concentrations of icaritin, in order to explore the possible molecular mechanisms. The research object was ovarian cancer SKOV3 cells. The cells were divided into the control group and icaritin groups(5, 10, 20 µmol·L~(-1)), and administrated with drugs for 48 hours. The cell counting kit-8(CCK-8)assay was used to detect the inhibitory effect of icaritin on the proliferation of ovarian cancer SKOV3 cells. The proliferation ability of the SKOV3 cells was detected by EdU assay. Hoechst 33342 fluorescence staining was used to observe the apoptotic morphology of SKOV3 cells in each group. The distribution of cell cycle and the apoptosis rate of each group were detected by flow cytometry. Quantitative Real-time PCR was used to detect mRNA expressions of PTEN, PI3K, Akt in each group of cells. Protein expressions of PTEN, PI3K, Akt and p-Akt were measured by Western blot. The results showed that the cell inhibition rates of icaritin groups were significantly increased compared with the control group(P<0.05). The rates of EdU-positive cells of icaritin groups were significantly decreased(P<0.05). SKOV3 cells in icaritin groups showed morphological changes of apoptosis. Apoptosis rates of icaritin groups were significantly increased(P<0.05). The proportions of cells in G_0/G_1 phase of icaritin groups were decreased(P<0.05), while the proportions of S phase cells were increased(P<0.05). The gene and protein expressions of PTEN in icaritin groups were elevated(P<0.05). The gene expressions of PI3K and Akt in icaritin groups were down-regulated(P<0.05). The protein expression of PI3K and p-Akt in icaritin groups were reduced(P<0.05). These results indicated that icarin may inhibit the proliferation of ovarian cancer SKOV3 cells in vitro, induce cell apoptosis and affect the cycle distribution of cells by inhibiting the PI3K/Akt signaling pathway.

Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique.

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CLpro ), and an in vitro drug screening model based on fluorescence resonance energy transfer was used to evaluate its inhibitory activity in vitro. The fingerprint results showed that the alcohol extract of Liupao tea contained gallic acid, epigallocatechin gallate (EGCG), caffeine, epicatechin gallate, rutin, and ellagic acid. The molecular docking binding energies of the six index components of SARS-CoV-2 3Clpro were all less than -5.0 kJ/mol and showed strong binding affinity. The results of in vitro activity showed that the IC50 of EGCG was 8.84 µmol/L, which could inhibit SARS-CoV-2 3Clpro to a certain extent. This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19. PRACTICAL APPLICATIONS: The objective of this study was to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor. We predicted that the understandings gained in the current research may evidence that Liupao tea has a certain significance as a tea drink for the prevention of COVID-19.

Aurantio-obtusin improves obesity and insulin resistance induced by high-fat diet in obese mice.

Aurantio-obtusin (AUR) is the main bioactive compound among the anthraquinones, from Cassia seed extract. This study was conducted to identify whether AUR could improve obesity and insulin resistance, induced by a high-fat diet in obese mice. Mice were fed a high-fat diet for 6 weeks and were then assigned to the high-fat diet (HFD) control group, the AUR 5 mg/kg group, or the AUR 10 mg/kg group. AUR improves glucose by activating the expression of PI3K, Akt and GLUT4, GLUT2. AUR altered the expression levels of several lipid metabolism-related and adipokine genes. AUR decreased the mRNA expression of PPAR-γ, FAS and increased the mRNA expression of PPAR-α in liver. AUR lowered SREBP-1c, FAS, SCD-1, inflammatory cytokines, and increased the expression of PPAR-γ, PPAR-α, CPT-1, and adiponectin in white adipose tissue (WAT). AUR docking with the insulin receptor showed that the residues of the insulin receptor, ectodomain, were the same as those around the emodin. The effect of AUR may be elicited by regulating the activity of the insulin signaling pathway, expression of lipid metabolism-related genes, and expression of inflammatory cytokine markers to improve adiposity, insulin resistance, and dyslipidemia.

[Clinical effect of Liyan Tongqiao acupuncture in treatment of post-stroke dysphagia: an analysis based on diffusion tensor imaging].

OBJECTIVE: To investigate the clinical change of post-stroke dysphagia after the intervention of Liyan Tongqiao （relieving sore-throat and dredging orifices）acupuncture using cranial diffusion tensor imaging (DTI). METHODS: A total of 60 patients with post-stroke dysphagia were enrolled and randomly divided into Liyan Tongqiao acupuncture group and neurology treatment group, with 30 patients in each group. The patients in the neurology treatment group were given routine neurology treatment and swallowing rehabilitation training, and those in the Liyan Tongqiao acupuncture group received acupuncture at Sishencong (EX-HN1), Baihui (GV20), bilateral Tai-yang (EX-HN5), and bilateral Fengchi (GB20) and tongue triple acupuncture, with an electroacupuncture apparatus for EX-HN1, bilateral GB20, and tongue triple acupuncture, for a needle retaining time of 30 minutes each time, once a day and 5 times a week, in addition to the treatment in the neurology treatment group. Each course of treatment was 3 weeks, and both groups were treated for 2 courses. Swallowing function assessment and cranial DTI were performed after treatment. RESULTS: After 6 weeks of treatment, both groups had a marked improvement in swallowing function, a significantly greater change in video fluoroscopic swallowing study (VFSS) score and a higher mean FA value (P<0.05). Compared with the neurology treatment group, the Liyan Tongqiao acupuncture group had a marked improvement in swallowing function, a significantly greater change in VFSS score in the pharyngeal phase and a higher mean FA value (P<0.05). CONCLUSION: Liyan Tongqiao acupuncture can improve dysphagia and swallowing function in the pharyngeal phase in VFSS, possibly by promoting the remodeling of cerebral cortex and increasing the FA value of infarct zone through the stimulation of related acupoint signals.

Sipi soup inhibits cancer­associated fibroblast activation and the inflammatory process by downregulating long non­coding RNA HIPK1­AS.

Sipi soup (SPS), the aqueous extract derived from the root bark of Sophora japonical L, Salix babylonica L., Morus alba L., as well as Amygdalus davidiana (Carr.) C. de Vos, is a traditional Chinese medicine frequently used to prevent and treat infection and inflammation. However, the role of SPS in cancer­associated fibroblasts (CAFs) require further investigation. In the present study, the effects of SPS on fibroblast inactivation and the underlying mechanism were investigated. Reverse transcription­quantitative polymerase chain reaction was used to analyze the mRNA expression levels of fibroblast activation protein (FAP), interleukin (IL)­6, α­smooth muscle actin (α­SMA) and programmed cell death 4 (PDCD4). Flow cytometry was used to evaluate cell apoptosis. Immunofluorescence was used to determine the number of activated fibroblasts. The present study reported that SPS treatment did not affect the proliferative apoptotic potential of fibroblasts. Treatment with HeLa cell culture medium (CM) induced a significant increase in the expression levels of FAP, IL­6 and α­SMA, but reduced the expression of PDCD4. SPS reversed the effects of HeLa CM on the expression of these genes. Analysis with a long non­coding (lnc)RNA array of numerous differentially expressed lncRNAs revealed that the expression levels of the lncRNA homeodomain­interacting protein kinase 1 antisense RNA (HIPK1­AS) were increased in cervicitis tissues and cervical squamous cell carcinoma tissues compared with in normal cervical tissues. HIPK1­AS expression levels were upregulated in response to HeLa CM, but were decreased under SPS treatment. The downregulation of HIPK1­AS expression via short hairpin RNA abolished the effects of HeLa CM on the expression of inflammation­associated genes. The findings of the present study suggested that SPS may prevent the progression of cervical cancer by inhibiting the activation of CAF and the inflammatory process by reducing HIPK1­AS expression.

New Phloroglucinol Derivatives from the Fruit Tree Syzygium jambos and Their Cytotoxic and Antioxidant Activities.

Seven new phloroglucinol derivatives (1-7) were isolated from the fruit tree Syzygium jambos together with four known triterpenoids (8-11) and two known flavones (12 and 13). According to the spectroscopic analyses (infrared, electrospray ionization mass spectrometry (ESIMS), high-resolution ESIMS, 1D and 2D nuclear magnetic resonance), the structures of compounds 1-7 were elucidated as jambone A (1), jambone B (2), jambone C (3), jambone D (4), jambone E (5), jambone F (6), and jambone G (7). All the isolates were determined for their cytotoxic activities on melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and compounds 10 and 11 showed potent activities. Moreover, compounds 1, 2, 4-7, 12, and 13 exhibited weak antioxidant activities under ferric-reducing antioxidant power and 2,2-diphenyl-1-picryhydrazyl radical-scavenging assays.

A new diterpenoid from the aerial parts of Andrographis paniculata.

One new and seven known diterpenoids were isolated from the aerial parts of Andrographis paniculata, and their structures elucidated on the basis of spectroscopic and spectrometric analysis, as well as chemical methods. The in vitro antiviral activities of these compounds against respiratory syncytial virus (RSV) were assayed.

[Efficacy on perennial allergic rhinitis treated with acupuncture at three nasal poinits and the acupoints selected by syndrome differentiation].

OBJECTIVE: To compare the difference in the clinical efficacy on perennial allergic rhinitis between three nasal points acupuncture therapy and the oral administration of loratadine so as to provide the better acupuncture program in clinical treatment. METHODS: Sixty cases were randomized into an acupuncture group (30 cases) and a medication group (30 cases). In the acupuncture group, acupuncture was applied to three nasal points [Yingxiang (LI 20), Yintang (EX-HN 3), Bitong (Extra)] and acupoints selected by syndrome differentiation. Acupuncture was given once every two days, three times a week, for 4 weeks totally. In the medication group, loratadine was prescribed for oral administration, 10 mg every day, for 4 weeks. The symptom and physical sign scores before and after treatment, as well the short-term and long-term efficacy were compared between the two groups. RESULTS: The total effective rate was 96.7% (29/30) in the acupuncture group and was 93.3% (28/30) in the medication group after treatment. The efficacy was similar between the two groups (P>0.05). In follow-up, the total effective rate was 86.7% (26/30) in the acupuncture group, which was better than 56.7% (17/30, P<0.05) in the medication group. The scores of symptoms and physical signs after treatment and in follow-up were all reduced apparently as compared with those before treatment in the patients of the two groups (all P<0.05). The scores of symptoms and physical signs were reduced more apparently in the acupuncture group as compared with those in the medication group in follow-up (all P<0.05). CONCLUSION: The acupuncture at three nasal points and the acupoints selected by syndrome differentiation achieves the similar short-term efficacy on perennial allergic rhinitis as compared with the oral administration of loratadine. The acupuncture therapy presents the obvious advantages on long-term efficacy.

[Effect of Xinmaitong capsule on serum matrix metalloproteinases-9, high sensitive C-reactive protein levels in patients with acute coronary syndrome].

OBJECTIVE: To observe the influence of Xinmaitong capsule (XMT) on serum matrix metalloproteinases-9, high sensitive C-reactive protein levels in patients with acute coronary syndrome. METHOD: 63 cases were divided by randomized, contrastive assigned to XMT group (n = 31) and control group (n = 32). The serum levels of MMP-9 and hs-CRP before and after treatment in 12 weeks were detected. RESULT: After treatment, the serum levels of MMP-9 in control group had no changed and the levels of hs-CRP reduced. The serum levels of MMP-9 and hs-CRP in XMT group had significantly decreased. The serum levels of MMP-9 and hs-CRP had positive correlation, but had no correlation to levels of serum lipids. CONCLUSION: XMT decreased breakdown of matrix collagen, and inflammatory reaction in the patients of ACS, which may have effect on plaque stabilization.

[Effect of capsule yindanxinnaotong (YD) on blood hemorheology and the score of blood stasis in patients with MS complicated ACS].

OBJECTIVE: To observe the effect of Capsule YD on blood hemorheology and the score of blood stasis in patients with MS complicated ACS, and to investigate the clinical effect of Chinese medicine of promoting blood flow on those diseases. METHODS: 63 cases were divided into two groups. Control group was treated with routine methods and YD group with additional YD. The course of treatment was 3 months. Blood hemorheology and the score of blood stasis were observed. RESULTS: Blood viscosity high shear rate, fibrinogen, the index and deformed index of Erythrocyte aggregation before and after treatment in both groups were improved (P < 0.05). And the index of Erythrocyte aggregation in YD group was significantly improved comparing to that in control group (P < 0.05). The symtom of stethalgia, frequency of episode, and blood stasis on tongue, lip and gums were also improved in YD group. The value of blood stasis in YD group was significantly decreased comparing to that in control group. CONCLUSIONS: Capsule YD can improve the angina pectoris and decrease the value of blood stasis in patients with ACS, and also improve their hemorheology. We should presume the Chinese medicine of activating blood circulation to dissipate blood stasis improve the metabolism and treat angina pectoris by improving blood hyperviscosity.