Anthocyanin Extracted from Purple Sweet Potato Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Suppressing Pyroptosis and Altering Intestinal Flora Structure.

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS) in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group): DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. The DSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefully monitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessment was conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels of IL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-α, N-GSDMS, and cleaved-IL-1ß proteins were evaluated by Western blot analysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gut microbiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-induced UC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, and significantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1ß, and TNF-α, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria and Deferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviated DSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gut microbiota.

Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

Therapeutic effects of shikonin on adjuvant-induced arthritis in rats and cellular inflammation, migration and invasion of rheumatoid fibroblast-like synoviocytes via blocking the activation of Wnt/ß-catenin pathway.

BACKGROUND: Shikonin (SKN), the main bioactive component isolated from Lithospermum erythrorhizon Sieb et Zucc, has multiple activities including anti-rheumatic effect, but its specific roles and the precise mechanisms in regulating biological properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) are unclear and need further clarification. PURPOSE: This study explored the therapeutic roles of SKN on rat adjuvant-induced arthritis (AIA) and cellular inflammation, migration and invasion of TNF-α-induced RA FLS (MH7A cells), and further demonstrated the involved mechanisms. METHODS: SKN was intraperitoneally given to AIA rats and its therapeutic role was valued. The effects of SKN in vivo and in vitro on the production of pro-inflammatory factors were examined by ELISA and western blot. Wound-healing, transwell and phalloidin staining assay were carried out to evaluate the effects of SKN on TNF-α-induced migration and invasion in RA FLS. The involvement of Wnt/ß-catenin pathway was checked by immunohistochemistry or immunofluorescence assay for ß-catenin and western blot for pathway-related proteins. RESULTS: SKN treatment in AIA rats reduced paw swelling, arthritis index and pathological damage of ankle joints, indicating its anti-arthritic effect in vivo. SKN had anti-inflammatory roles in vivo and in vitro, evidenced by inhibiting the production of pro-inflammatory factors (like IL-1ß, IL-6, IL-8, TNF-α, MMP-2 and MMP-9) in sera and synovium of AIA rats, and in TNF-α-induced MH7A cells. Gelatin zymography result revealed the suppression of SKN on TNF-α-induced MMP-2 activity in vitro. Moreover, SKN inhibited TNF-α-induced migration, invasion and cytoskeletal reorganization in MH7A cells. Mechanistically, SKN suppressed the activation of Wnt/ß-catenin signaling in AIA rat synovium and in TNF-α-induced MH7A cells, indicated by the reduced protein levels of Wnt1, p-GSK-3ß (Ser9) and ß-catenin, the raised protein level of GSK-3ß and the decreased nuclear translocation of ß-catenin. Interestingly, the combination of LiCl (Wnt/ß-catenin agonist) canceled the therapeutic functions of SKN on cellular inflammation, migration and invasion in TNF-α-induced MH7A cells, whereas XAV939 (Wnt/ß-catenin inhibitor) enhanced the therapeutic roles of SKN. CONCLUSION: SKN showed therapeutic effects on rat AIA and cellular inflammation, migration and invasion of TNF-α-stimulated RA FLS via interrupting Wnt/ß-catenin pathway.

Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro-inflammatory cytokine production.

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.

1α,25-dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid-induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response.

Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ). Our results showed that 1α,25(OH)2 D3 intervention significantly improved PFOS-induced sperm quality decline and testicular damage. Moreover, 1α,25(OH)2 D3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH)2 D3 ameliorated PFOS-induced augment of Nrf2 and target genes. These findings indicated that 1α,25(OH)2 D3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress.

Celastrol enhances bone wound healing in rats.

Bone fracture is one of the most common injuries in the human musculoskeletal system. This study was performed to investigate the effects of celastrol on bone wound healing in rats. Bone wound models of Sprague-Dawley rats were treated with low (10 µg/kg) and high (100 µg/kg) celastrol for 14 days. Serum calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) contents, bone mechanical properties, bone mineral density (BMD), and the levels of osteogenesis-related and inflammation-related proteins were assessed at the end of the experiments. Rats feeding with celastrol grew normally as control. Compared with model, celastrol administration significantly increased fracture strength, elastic load (0.12 vs 0.16 kg/m), bending energy (11.23 vs 14.23 n x mm), and BMD (0.49 vs 0.54 g/cm3), particularly at a high dose. Serum Ca (2.2 vs 2.7 mmol/L) and ALP (217.3 vs 245.8 IU/L) contents were significantly increased after a high dose celastrol administration, although P content did not change. Western blot analyses showed that OPG (0.72 vs 1.15) and COL-1 (0.20 vs 0.42) but not RUNX2 were upregulated significantly after celastrol administration, and IL-1α (0.82 vs 0.37), IL-6 (0.62 vs 0.28), MCP-1(0.68 vs 0.18), and VEGF (0.62 vs 0.42) were significantly downregulated, while IFN-γ was upregulated (0.29 vs 0.46). Our data demonstrate that celastrol effectively promotes the healing of bone wound in rats and may be further explored as a therapeutic agent to treat bone fracture.

A Bio-Based Supramolecular Adhesive: Ultra-High Adhesion Strengths at both Ambient and Cryogenic Temperatures and Excellent Multi-Reusability.

Developing high-performance and reusable adhesives from renewable feedstocks is of significance to sustainable development, yet it still remains a formidable task. Herein, castor oil, melevodopa, and iron ions are used as building blocks to construct a novel bio-based supramolecular adhesive (BSA) with outstanding adhesion performances. It is prepared through partial coordination between melevodopa functionalized castor oil and Fe3+ ions. Noncovalent interactions between adherends and the catechol unit from melevodopa contribute to reinforcing adhesion, and the metal-ligand coordination between catechol and Fe3+ ions is utilized to strengthen cohesion. By combining strong adhesion and tough cohesion, the prepared BSA achieves an adhesion strength of 14.6 MPa at ambient temperature, a record-high value among reported bio-based adhesives as well as supramolecular adhesives to the best of knowledge. It also outperforms those adhesives at cryogenic temperature, realizing another record-high adhesion strength of 9.5 MPa at -196 °C. In addition, the BSA displays excellent multi-reusability with more than 87% of the original adhesion strength remaining even after reuse for ten times. It is highly anticipated that this line of research will provide a new insight into designing bio-based adhesives with outstanding adhesion performances and excellent multi-reusability.

Umbelliferone Inhibits Migration, Invasion and Inflammation of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Relieves Adjuvant-Induced Arthritis in Rats by Blockade of Wnt/ß-Catenin Signaling Pathway.

Umbelliferone (UMB), a natural coumarin compound, has been reported to possess anti-rheumatic effects on rheumatoid arthritis (RA) experimental models, but its potential role of UMB in regulating migration, invasion and inflammation of RA fibroblast-like synoviocytes (FLS) remain unclear. Herein, MTT assay was performed to confirm the non-cytotoxic concentrations (10, 20, and 40[Formula: see text][Formula: see text]M) and the treatment time (24[Formula: see text]h) of UMB on TNF-[Formula: see text]-stimulated RA FLS (MH7A cells) in vitro. Results of wound-healing, transwell and phalloidin staining assays revealed that UMB inhibited TNF-[Formula: see text]-induced migration, invasion and F-actin cytoskeletal reorganization in MH7A. Results of ELISA, western blot and gelatin zymography indicated that UMB decreased the productions of pro-inflammatory factors, including IL-1[Formula: see text], IL-6, IL-8, MMP-2 and MMP-9, and inhibited MMP-2 activity in TNF-[Formula: see text]-stimulated MH7A cells. In vivo, UMB (25[Formula: see text]mg/kg and 50[Formula: see text]mg/kg) relieved the joint damage and synovial inflammation in rats with adjuvant-induced arthritis (AIA). Mechanistically, UMB could suppress Wnt/[Formula: see text]-catenin signaling both in TNF-[Formula: see text]-induced MH7A cells and in AIA rat synovium, evidenced by decreasing Wnt1 protein level, activating GSK-3[Formula: see text] kinase by blocking GSK-3[Formula: see text] (Ser9) phosphorylation, and reducing the protein level and nuclear translocation of [Formula: see text]-catenin. Importantly, combined use of lithium chloride (a Wnt/[Formula: see text]-catenin signaling agonist) eliminated the inhibitory effects of UMB on migration, invasion and inflammation in vitro and the anti-arthritic effects of UMB in vivo. We concluded that UMB inhibited TNF-[Formula: see text]-induced migration, invasion and inflammation of RA FLS and attenuated the severity of rat AIA through its ability to block Wnt/[Formula: see text]-catenin signaling pathway.

A combination of electroacupuncture and auricular acupuncture for postoperative pain after abdominal surgery for gynaecological diseases: A randomized controlled trial.

BACKGROUND: Postoperative pain following laparotomy for gynaecological diseases is a common problem that requires effective management to ensure patient satisfaction and recovery. Despite the wide use of acupuncture for pain management, knowledge of its efficacy in managing postoperative pain is limited. Previous literature used either acupuncture or auricular acupuncture alone. However, the combined use of acupuncture and auricular acupuncture have not been studied yet. PURPOSE: This study examined the efficacy and feasibility of combined electroacupuncture and auricular acupuncture compared to a sham control in reducing pain during 5 days after a laparotomy for gynaecological diseases. This combined therapy was hypothesized to provide greater pain reduction than previous studies with less frequent treatment. STUDY DESIGN: Randomized sham-controlled, patient- and- assessor-blinded trial. METHODS: This trial recruited 72 patients scheduled for laparotomy in Hong Kong. Either acupuncture (n = 36) or non-invasive sham acupuncture (n = 36) was performed on the patients preoperatively (1 session) and postoperatively (once a day, up to 6 sessions). The primary outcome was pain at rest, measured using a numerical rating scale from postoperative days 0-5. Secondary outcomes such as analgesics consumption were also assessed. A data and safety monitoring board (DSMB) was established. RESULTS: All 72 randomized patients were included in the analysis. The acupuncture group had a smaller pain score at rest at 22 hrs (mean = 2.6) than the sham control group (mean = 4.0) (Post hoc intention to treat analysis, Linear regression, mean difference = -1.4, 95% confidence interval = [-0.2] -2.7, p = 0.029). No statistically significant between-group difference was found in other outcomes. No serious adverse event was observed. CONCLUSION: Perioperative acupuncture treatments are safe and feasible, but the efficacy of acupuncture is inconclusive.

Simultaneous and efficient removal of fluoride and phosphate in phosphogypsum leachate by acid-modified sulfoaluminate cement.

The high concentration of fluoride and phosphate in phosphogypsum leachate is harmful to the environment and ecosystem. Thus, there is a need to develop feasible materials or technologies to remove both fluoride and phosphate in acidic phosphogypsum leachate. In this study, sulfoaluminate cement (SC) was used to simultaneously remove fluoride and phosphate in wastewater based on its moderate alkalinity and rich content of metal elements (Ca, Al and Fe, etc). The acidized sulfoaluminate cement (ASC) composite was prepared through modifying SC with hydrochloric acid, which can increase the specific surface areas of the raw SC, as well as the activity of the metal elements in SC. Compared with other coagulants, ASC showed excellent removal performance for fluoride and phosphate, such as higher removal efficiency, better effluent quality, and accelerated settling rate. The fluoride and phosphate removal performances of ASC herein were investigated at different dosages, pH values, coexisting substances, and initial concentrations. As a result, ASC exhibited wide pH adaptability and satisfactory selectivity for fluoride and phosphate. The possible removal mechanisms of fluoride and phosphate by ASC included chemisorption, ion exchange, and precipitation. The main end products associated with fluoride were fluorite (CaF2), aluminum fluoride (AlF3), and iron trifluoride (FeF3). The main final products amid phosphate removal, on the other hand, were brushite (CaHPO4·2H2O), aluminophosphate ((H3O)·AlP2O6(OH)2), silicocarnotite (Ca2SiO4·Ca3(PO4)2) and iron phosphate (Fe(H2PO4)3). More importantly, ASC can effectively treat the phosphogypsum leachate at a wide range of concentrations, and the concentrations of phosphate and fluoride in the effluents were lower than 0.5 mg P L-1 and 4 mg L-1, respectively. To sum up, ASC is a competitive candidate to treat wastewater with high fluoride and phosphate content, such as phosphogypsum leachate.

The global status of research in breast cancer liver metastasis: a bibliometric and visualized analysis.

This study aimed to investigate the distribution laws and research frontiers of international literature, so as to present a holistic bibliometric evaluation of the studies on breast cancer liver metastasis(BCLM). Data were collected from the Web of Science Core Collection database, including publications, year, country, journal, author and keywords. The software VOSviewer and CiteSpace were used for bibliometric coupling, co-authorship, co-citation and co-occurrence analysis. In total, 1,031 publications were analyzed from 2004 to 2020 on BCLM. The year with the highest number of publications was 2006, with 103 papers. The United States, followed by China and Germany were the leading countries on BCLM, accounting for 59% of the whole. The journals that published about BCLM were mainly located in Q1/Q2. Keywords co-occurrence analysis divides BCLM into five clusters:'basic research', 'auxiliary diagnosis and therapy', 'liver resection', 'clinical trial' and 'prognosis'. Main treatment therapies were the latest focus. Burst detection indicated that the trends in BCLM concentrated on subtype and SEER. There is apparently brighter perspective for BCLM research in the coming years, especially in liver resection, subtype and bioinformatics. The consequence of our study as the exclusive scientific evaluation offered an integral overview of BCLM, particularly for research focus and future directions, which can further accurately guide scholars on diagnosis, treatment, and personalized prevention.

Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial.

OBJECTIVE: Insomnia is a highly prevalent and disturbing symptom in breast cancer patients under or post chemotherapy. If not appropriately treated, it can persist for years after the completion of cancer treatments. Acupuncture has been widely used for alleviating insomnia. The aim of this study is to examine the feasibility, efficacy and safety of acupuncture for chemotherapy-related insomnia among patients with breast cancer. MATERIALS AND METHODS: This is a trial protocol for a randomized, sham-controlled, subject- and assessor-blinded clinical trial. A total of 138 eligible participants will be assigned randomly to acupuncture or sham control group at a ratio of 1:1. Participants in acupuncture group will receive electroacupuncture (EA) plus auricular acupressure (AA) treatment, while subjects in sham acupuncture group will receive sham EA plus sham AA. Both acupuncture and sham treatments will be given twice weekly for 6 weeks, followed by maintenance treatments once every 4 weeks for 12 weeks (15 sessions totally). The primary outcome is the change of Insomnia Severity Index score between baseline and the end of 6-week treatment. Secondary outcome measurements include Actiwatch, sleep diary, Pittsburgh Sleep Quality Index, Functional Assessment of Cancer Therapy-Breast Cancer, Hospital Anxiety and Depression Scale, Brief Pain Inventory-Short Form, Brief Fatigue Inventory, Acupuncture Expectancy Scale, credibility, and adverse events. Participants will be followed up to 42 weeks. CONCLUSIONS: This trial will expand our understanding of the feasibility, efficacy, and safety of acupuncture as a treatment for alleviating chemotherapy-related insomnia in patients with breast cancer. EA plus AA, if proven to be effective, can be implemented into routine settings to play a role in insomnia management for patients with breast cancer.

Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection.

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.

Contribution of traditional Chinese medicine combined with conventional western medicine treatment for the novel coronavirus disease (COVID-19), current evidence with systematic review and meta-analysis.

This study provides current evidence for efficacy and safety of treating COVID-19 with combined traditional Chinese medicine (TCM) and conventional western medicine (CWM). Six databases were searched from January 1 to December 31, 2020. Randomized controlled trials (RCTs), case-control studies (CCTs), and cohort studies on TCM or TCM combined with CWM treatment for COVID-19 were included. The quality of included RCTs was assessed by Cochrane risk of bias tool, and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort studies and CCTs. Review Manager 5.4 software was used to perform meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 35 studies (3,808 patients) composing 19 RCTs and 16 observational studies were included. The results of meta-analysis revealed that comparing with CWM alone, integrated TCM and CWM had significant improvement in total effective rate, improvement rate of chest CT, the rate of disease progression, as well as improvement of fever, fatigue and cough. The overall quality of evidence was very low to moderate. In conclusion, TCM combined with CWM was a potential treatment option for increasing clinical effective rate, improving the clinical symptoms, and preventing disease progression in COVID-19 patients. High-quality clinical trials are required in the further.

Superficial Needling Acupuncture vs Sham Acupuncture for Knee Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: Acupuncture has been an alternative approach for pain management, but trial evidence is conflicting. METHODS: Eighty-six patients with knee osteoarthritis were randomly assigned in a 1:1 ratio from June 14, 2017, to January 20, 2019, to receive either superficial needling acupuncture treatment or sham acupuncture for 10 sessions over a 4-week treatment period, followed by a 6-week follow-up period. The primary outcome was the change of pain intensity at week 4 measured using a 100-mm visual analogue scale. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index and 36-Item Short Form Health Survey. RESULTS: At the end of the 4-week treatment period, mean changes in the visual analogue scale were -30.8 (95% confidence interval [CI], -38.2 to -23.0; p <.001) in the acupuncture group and -26.7 (95% CI, -34.4 to -18.8; P <.001) in the sham group. The difference between the acupuncture group and the sham group was -4.1 (95% CI, -14.4 to 6.2; P = 0.431). At week 10, the difference between the groups was -2.2 (95% CI, -13.1 to 8.8; P =0.699). There was no statistically significant difference in Western Ontario and McMaster Universities Osteoarthritis Index subscores (pain, stiffness, and physical function) and 36-Item Short Form Health Survey-related outcomes across groups from weeks 2 to 10. The incidence of treatment-related adverse events was 4.4% in the acupuncture group and 0.8% in the sham acupuncture group. All adverse events were classified as mild. CONCLUSION: Acupuncture for 4 weeks is not superior to non-penetrating sham acupuncture. The current study cannot confirm that superficial acupuncture has efficacy for the treatment of knee osteoarthritis.

The Adjunctive Effect of Acupuncture for Advanced Cancer Patients in a Collaborative Model of Palliative Care: Study Protocol for a 3-Arm Randomized Trial.

BACKGROUND: Cancer is the second leading cause of death before the age of 70. Improved cancer survival has put increasing demands on cancer care. Palliative care is the specialized multi-disciplinary care providing relief from the pain, symptoms, and stress of serious illness. The study aims to evaluate the adjunctive effect of acupuncture for advanced cancer patients in a collaborative model of palliative care. METHODS/DESIGN: This is a single-blinded, randomized, sham-controlled trial. One hundred twenty advanced cancer patients undergoing palliative care will be randomized in a ratio of 2:1:1 to manual acupuncture plus standard care group (ASC), sham acupuncture plus standard care group (SSC), and standard care group (SC). Patients in ASC and SSC will receive 9 sessions of acupuncture or sham acupuncture for 3 weeks, and will be followed up for 2 months. The primary measure is the change from baseline score of the Edmonton Symptom Assessment System at 3 weeks. The secondary measures include the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Numeric Rating Scale, and European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care. DISCUSSION: The finding of this trial will provide high-quality evidence on the adjunctive effect of acupuncture to standard care on advanced cancer patients undergoing palliative care. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04398875 (https://www.clinicaltrials.gov/ct2/show/NCT04398875), Registered on 21 May 2020.

[Mechanism of Danggui Sini Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking].

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.

Riparian buffer effectiveness as a function of buffer design and input loads.

Although many agricultural watersheds rely heavily on riparian buffer adoption to meet water quality goals, design and management constraints in current policies create adoption barriers. Based on focus group feedback, we developed a flexible buffer design paradigm that varies buffer width, vegetation, and harvesting. Sixteen years of daily-scale nutrient and sediment loads simulated with the Soil and Water Assessment Tool (SWAT) were coupled to the three-zone Riparian Ecosystem Management Model (REMM) to compare the effectiveness of traditional, policy-based buffer designs with designs that are more flexible and integrate features important to local farmers. Buffer designs included (i) 10 m grass, (ii) 15 m grass, (iii) 15 m deciduous trees, (iv) 30 m grass and trees, (v) 30 m grass and trees with trees harvested every 3 yr, and (vi) 30 m grass and trees with grass harvested every year. Allowing harvesting in one zone of the buffer vegetation (either trees or grasses) minimally affected water quality, with annual average percent reductions differing by <5% (p > .05; 76-78% for total nitrogen [TN], 51-55% for total phosphorus [TP], and 68% for sediment). Under the highest input loading conditions, buffers with lower removal efficiencies removed more total mass than did buffers with high removal efficiencies. Thus, by focusing on mass reduction in addition to percent reduction, watershed-wide buffer implementation may be better targeted to TN, TP, and sediment reduced. These findings have important implications for informing flexible buffer design policies and enhanced placement of buffers in watersheds impaired by nutrient and sediment.

Metabolic profiling of rats poisoned with paraquat and treated with Xuebijing using a UPLC-QTOF-MS/MS metabolomics approach.

Xuebijing (XBJ) is a compound Chinese medicine that contains Paeoniae Radix Rubra, ChuanXiong Rhizoma, Salvia Miltiorrhiza Radix et Rhizoma, Carthami Flos, and Angelicae Sinensis Radix. It is widely used in China to treat sepsis. Previous studies have demonstrated that XBJ can decrease mortality in patients with moderate paraquat poisoning. However, the mechanism by which it exerts this effect is not completely clear. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was used to perform a metabolic profiling analysis. Principal component analysis (PCA), random forest (RF), and partial least squares discriminant analysis (PLS-DA) were used to identify metabolites to clarify the mechanism of XBJ's activity. XBJ clearly alleviated lung injury in a Sprague Dawley (SD) rat model of paraquat (PQ) poisoning. Seven metabolites related to four pathways, including those involved in sphingolipid and phospholipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism, and pantothenic acid and CoA biosynthesis, were present at different levels in PQ-poisoned rats treated with XBJ compared with untreated rats. XBJ can ameliorate the effects of PQ poisoning in SD rats. Using a metabolomics approach enabled us to gain new insight into the mechanism underlying this effect.

Effect of Oral Glucose Water Administration 1 Hour Preoperatively in Children with Cyanotic Congenital Heart Disease: A Randomized Controlled Trial.

BACKGROUND Guidelines recommend a clear liquid fasting time of 2 h before surgery, which is often exceeded, leading to adverse reactions (ARs) such as discomfort, thirst, and dehydration. We assessed the gastric contents and ARs after oral glucose water administration 1 h prior to surgery in children with cyanotic congenital heart disease (CCHD). MATERIAL AND METHODS This was a non-inferiority randomized controlled trial of children with CCHD enrolled at the Fujian Medical University Union Hospital from 09/2014 to 05/2017 and randomized to receive oral glucose water (10 g of glucose in 100 ml of warm water, 5 ml/kg) 2 h (2-h group, n=174) or 1 h (1-h group, n=170) before surgery. The primary endpoint was gastric volume. Secondary endpoints included pH of gastric content, preoperative blood glucose, and risk factors for aspiration pneumonia. Pre- and intraoperative ARs were recorded. RESULTS The 1-h group showed smaller gastric content volumes (0.34±0.35 (95% CI: 0.29-0.39) vs. 0.43±0.33 (95% CI: 0.38-0.48) ml/kg, t=2.55, P<0.05) and higher blood glucose (6.21±0.78 (95% CI: 6.09-6.33) vs. 5.59±1.11 (95% CI: 5.43-5.76) mmol/L, t=-5.91, P<0.001). The 95% confidence interval of the volume difference between the 2 groups was 0.017-0.163, the upper limit value was 0.163