Green synthesis and characterization of an orally bioactive artemisinin-zinc nanoparticle with enhanced bactericidal activity.

The occurrence of multidrug-resistant bacteria necessitates the development of new antibacterial agents. This study synthesized artemisinin-zinc nanoparticles (AZ NPs) using a simple green method and investigated their physicochemical properties, antibacterial activity, and oral biological activity. A spherical shape morphology of AZ NPs was observed by scanning and transmission electron microscopy, with a particle size of 73 ± 2.604 nm. Energy dispersive spectrometry analysis showed that the AZ NPs consisted mainly of Zn, C, N, and O elements. According to differential scanning calorimeter analysis, the AZ NPs were stable up to 450 °C. Fourier-transform infrared spectroscopy revealed that artemisinin successfully bound to zinc acetate. The AZ NPs showed antibacterial activity against Salmonella and Escherichia coli, with a minimum inhibitory concentration of 0.056 mg/mL for both and minimum bactericidal concentrations of 0.21 and 0.11 mg/mL, respectively. The mechanisms by which AZ NPs mediate membrane damage were revealed by the downregulation of gene expression, and potassium ion and protein leakage. In vivo safety trials of these drugs revealed low toxicity. After AZ NPs were administered to infected mice, the intestinal bacteria decreased significantly, liver and kidney function were restored, histopathological damage to the liver and spleen were reduced, and the expression of inflammatory cytokines decreased. Therefore, AZ NPs have the potential as an oral antibacterial agent and can be used in antibiotic development and in the pharmaceutical industry.

The Potential Mechanism of Curcumin in Treating Oral Squamous Cell Carcinoma Based on Integrated Bioinformatic Analysis.

Aims: This study explores the effects of curcumin as a therapeutic agent against oral squamous cell carcinoma (OSCC). Methods: We acquired the targets of curcumin from three digital databases, including the Comparative Toxicogenomics Database, Search Tool for Interactions of Chemicals, and SwissTargetPrediction. Then, we identified the differentially expressed genes (DEGs) and the weighted gene coexpression network analysis-based key modules using the expression profiles of GSE23558 to acquire the OSCC-related genes. Additionally, the GeneCards and Online Mendelian Inheritance in Man databases were also used to identify the OSCC-related genes. Finally, curcumin-OSCC interaction genes were obtained by overlapping curcumin targets and OSCC-related genes. The enrichment analysis was performed by the ClusterProfiler algorithm and Metascape, respectively. Then, a protein-protein interaction network was created, and the maximal clique centrality algorithm was used to identify the top 10 hub genes. Besides, we examined the expression levels of hub genes in OSCC using The Cancer Genome Atlas database. Results: 927 DEGs were identified, including 308 upregulated ones and 619 downregulated ones. The cluster one-step network construction function of the WGCNA algorithm recognized a soft-thresholding power of 6, and 9083 genes were acquired. 2591 OSCC-related genes were obtained by overlapping the GSE23558-identified genes and the OSCC-related genes from disease target bases. Finally, we identified 70 candidate drug-disease interaction genes by overlapping the disease-related genes with the curcumin target. The enrichment analysis suggested that response to oxidative stress, epithelial cell proliferation, and AGE/RAGE pathway might involve in the effect of curcumin on OSCC. The topologic study identified the ten hub genes, including VEGFA, AKT1, TNF, HIF1A, EGFR, JUN, STAT3, MMP9, EGF, and MAPK3. A significant difference was observed in VEGFA, AKT1, TNF, HIF1A, EGFR, MMP9, EGF, and MAPK3 expression levels between head and neck squamous cell carcinoma and the normal controls. However, no significant difference was observed in JUN (P = 0.14) and STAT3 (P = 0.054). Conclusion: This study provided an overview and basis for the potential mechanism of curcumin against OSCC. The following experiments should be performed to further understand the effectiveness and safety of curcumin in treating OSCC.

Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host.

Uropathogenic Escherichia coli (UPEC) is the main pathogen of recurrent urinary tract infections (RUTIs). Urinary tract infection is a complicated interaction between UPEC and the host. During infection, UPEC can evade the host's immune response and retain in bladder epithelial cells, which requires adequate nutritional support. Iron is the first necessary trace element in life and a key nutritional factor, making it an important part of the competition between UPEC and the host. On the one hand, UPEC grabs iron to satisfy its reproduction, on the other hand, the host relies on iron to build nutritional immunity defenses against UPEC. Ferritinophagy is a selective autophagy of ferritin mediated by nuclear receptor coactivator 4, which is not only a way for the host to regulate iron metabolism to maintain iron homeostasis, but also a key point of competition between the host and UPEC. Although recent studies have confirmed the role of ferritinophagy in the progression of many diseases, the mechanism of potential interactions between ferritinophagy in UPEC and the host is poorly understood. In this paper, we reviewed the potential mechanisms of ferritinophagy-mediated iron competition in the UPEC-host interactions. This competitive relationship, like a tug-of-war, is a confrontation between the capability of UPEC to capture iron and the host's nutritional immunity defense, which could be the trigger for RUTIs. Therefore, understanding ferritinophagy-mediated iron competition may provide new strategies for exploring effective antibiotic alternative therapies to prevent and treat RUTIs.

Manganese supplementation of orthopedic implants: a new strategy for enhancing integrin-mediated cellular responses.

Integrin-mediated osteoblast adhesion to adsorbed extracellular ligands on orthopedic implants is crucial for the subsequent osteoblast behaviors and ultimate osseointegration. Considerable research efforts have focused on the development of implant surfaces that promote the adsorption of extracellular ligands, but ignored the fact that integrin binding to ligands requires divalent cations (such as Mn2+). Here, three kinds of Mn-doped nanowire-structured TiO2 coatings with 1.9, 3.9, and 8.8 wt% dopant contents (Mn1-, Mn2-, and Mn3-TiO2) were synthesized on Ti implants to enhance integrin-mediated osteoblastic responses. The Mg-doped and undoped TiO2 nanocoatings served as the control. Mn element was not only successfully incorporated into the TiO2 matrix, but also formed an oxygen-deficient Mn oxide on the nanowire surface. Although the adsorbed fibronectin (Fn) amount on Mn-doped nanocoatings and its unfolded status were slightly attenuated with increasing Mn amount, the interaction between the coating extract and Fn demonstrated a Mn2+-induced unfolding of Fn with the exposure of the RGD motif. Compared to the Mn1-, Mn2- and Mg-doped TiO2 nanocoatings, the Mn3-TiO2 nanocoating significantly upregulated the expression of integrin α5ß1 probably through increasing the ligand-binding affinity of the integrin rather than integrin binding sites in Fn. Consistent with the activation trend of integrin α5ß1, the Mn3-TiO2 nanocoating enhanced cell adhesion with the long stretched structure of actin fibers and extensive formation of vinculin focal adhesion spots and upregulated the levels of alkaline phosphatase and osteocalcin activities. Therefore, Mn supplementation of orthopedic implants may be a promising way to improve osteogenesis at the implant surface.

QiHuangYiShen Granules Modulate the Expression of LncRNA MALAT1 and Attenuate Epithelial-Mesenchymal Transition in Kidney of Diabetic Nephropathy Rats.

Background: QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). Objective: In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/ß-catenin signal pathway. Methods: SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson's trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/ß-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. Results: The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, ß-catenin, and active ß-catenin. Conclusion: Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/ß-catenin pathway.

Clinical efficacy of Bupleurum inula flower soup for immune damage intervention in Hashimoto's thyroiditis: A placebo-controlled randomized trial.

Background: Antibody-mediated humoral immune response is involved in the damage process in Hashimoto's thyroiditis (HT). Although the traditional Chinese medicine (TCM) formula bupleurum inula flower soup (BIFS) is often used in HT treatment, it has not been evaluated through high-quality clinical research. Rigorously designed randomized, double-blind, prospective clinical studies are urgently needed to evaluate BIFS for intervening in the HT immune damage process, and to improve clinical prognosis and patient quality of life. Methods: A prospective randomized, double-blind, placebo-controlled trial was used to evaluate the efficacy of BIFS. Fifty participants diagnosed with HT with hypothyroidism were randomly assigned at a 1:1 ratio to the BIFS (levothyroxine with BIFS) or control (levothyroxine with placebo) group. Participants received 8 weeks of treatment and were followed for 24 weeks. They were monitored for: levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid stimulating hormone (TSH); scores for depression, anxiety, and health-related quality of life (HRQoL); thyroid volume; safety indicators including routine blood tests, liver and kidney functions, and electrocardiogram; and levothyroxine dose. Results: Forty-eight participants completed the study and were included in the final analysis. At baseline, there were no significant between-group differences in the observed indicators (p > 0.05). Post-treatment, compared with the control group, the BIFS group had significantly lower levels of TPOAb (275.77 ± 132.98 vs. 441.78 ± 195.50, p = 0.001), TgAb (385.92 ± 281.91 vs. 596.17 ± 282.26, p = 0.013), and TSH (6.57 ± 3.73 vs. 9.63 ± 5.34, p = 0.001). Compared with the control group, the BIFS group's scores improved significantly for depression (47.00 ± 5.12 vs. 51.04 ± 3.22, p = 0.002), anxiety (43.21 ± 4.22 vs. 48.08 ± 2.81, p = 0.005), and HRQoL physical (62.08 ± 5.97 vs. 57.96 ± 4.71, p = 0.011) and psychological (60.17 ± 5.94 vs. 55.75 ± 7.09, p = 0.024) subscores. At 24-week follow-up, levothyroxine combined with TCM allowed a significantly reduced levothyroxine dose (0.58 ± 0.43 vs. 1.02 ± 0.45, p = 0.001). The post-treatment clinical efficacy rates differed significantly (p = 0.03), with 75% (18/24) for the BIFS group and 46% (11/24) for the control group. There were no significant between-group differences in thyroid volume or safety indicators after eight treatment weeks or at the 24-week follow-up (p > 0.05). Conclusion: The TCM BIFS can effectively reduce thyroid titer, relieve clinical and emotional symptoms, and improve HRQoL in patients with HT. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR1900020987.

Nanomaterials based on phase change materials for antibacterial application.

Bacterial infections seriously threaten human health. Although antibiotics can significantly treat infectious diseases, antibiotics abuse has brought a series of serious problems, such as multidrug-resistant bacteria, adverse effects, and so on. Therefore, it is indispensable to develop alternative therapies with superior efficacy and minor toxicity to enhance the anti-infective outcome, overcome drug resistance and reduce adverse effects. The phase change material (PCM) is a substance that changes its physical properties with elevated temperatures. Nanoparticles based on PCM have been widely used in biomedical research due to their excellent biocompatibility, sustained release, and outstanding targeting properties. In this manuscript, the applications of PCM-based nanoparticles in the treatment of bacterial infections were summarized. Firstly, the composition and biotoxicity of PCM nanocarriers were described. Secondly, various antibacterial strategies based on PCM nanoparticles for combination therapy were highlighted. Finally, the prospects for antibacterial therapy of PCM nanomaterials were summarized.

Coupled microwave hydrothermal dechlorination and geopolymer preparation for the solidification/stabilization of heavy metals and chlorine in municipal solid waste incineration fly ash.

To improve the degradation efficiency of persistent organic pollutants (POPs) in municipal solid waste incineration fly ash (MSWIFA), as well as to overcome the difficulties of subsequent hydrothermal liquid and hydrothermal slag treatment, a two-step treatment strategy of microwave hydrothermal degradation coupled with geopolymer immobilization was proposed. Results showed that the optimal process parameters for microwave hydrothermal dechlorination were a temperature of 220 °C, a time of 1 h, and NaOH addition of 10 wt%. Microwaves accelerated the OH- mediated hydrolysis reactions and promoted the breaking of CCl bonds, leading to dechlorination. The compressive strength of the 20 % MSWIFA-based geopolymers reached 75.79 MPa, and the immobilization rate of the heavy metals (HMs) and Cl- surpassed 90 %. Alkaline environment provided by microwave hydrothermal promoted the formation of Ca(OH)2, which subsequently formed Friedel's salt (3CaO•Al2O3•CaCl2•10H2O) with Cl- in the geopolymer. The charge density difference and density of states (DOS) of Friedel's salt were analyzed by first-principles calculations, confirming that the existence of strong interactions between Ca-s, Al-p, O-p, and Cl-p states was the chemical mechanism of Cl- immobilization. The Friedel's salt and HMs were encapsulated by geopolymers with dense silica-alumina tetrahedral frameworks, achieving the solidification/stabilization (S/S) of HMs and Cl-. This work provided a new approach for the environmentally sound and resourceful treatment of MSWIFA.

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.

Elucidating the mechanism of Hongjinshen decoction in the treatment of pulmonary fibrosis based on network pharmacology and molecular docking.

BACKGROUND: To explore the mechanism of compound Hongginshen decoction in improving pulmonary fibrosis based on network pharmacology. METHODS: The active components and targets of ginseng and Salvia miltiorrhiza were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The chemical components of Rhodiola, Ophiopogon japonicus, and Dendrobium were screened using the Traditional Chinese Medicine Integrated Database (TCMID), and the target compounds were predicted by the Swisstargets method. The related target genes of pulmonary fiber (PF) were screened by the Genecards database and the National Center of Biotechnology Information (NCBI) database. The protein-protein interaction network was drawn using the string database and Cytoscape software, and the network topology was analyzed. Then, using R3.6.3 software, biological processes, molecular function, cell component enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out on the common targets of drugs and diseases. The network diagram of the "traditional Chinese medicine composition disease target" of Compound Hongginshen Decoction was constructed and analyzed with the software of Cytoscape 3.6.1. RESULTS: We identified 159 active components and 2820 targets in Compound Hongginshen Decoction, and 2680 targets in pulmonary fibrosis. A total of 343 common targets were obtained by the intersection of drug targets and disease targets. protein-protein interaction protein interaction network analysis showed that PIK3CA, PIK3R1, MAPK1, SRC, AKT1, and so on may be the core targets of the compound Hongjingshen recipe in the treatment of pulmonary fibrosis. Gene Ontology (GO) enrichment analysis identified 3463 items, and KEGG pathway enrichment analysis identified 181 related signaling pathways, including the PI3K-Akt signaling pathway, HCMV pathway, Hb pathway, PGs pathway, and KSHV signaling pathway. CONCLUSION: Compound Hongginshen Decoction has the characteristics of a multichannel and multitargeted effect in the treatment of pulmonary fibrosis. Radix Ophiopogonis and Dendrobium officinale play a key role in the treatment of pulmonary fibrosis. The whole compound prescription may play a therapeutic role by affecting cell metabolism, being anti-inflammatory, regulating the immune system, promoting angiogenesis, and improving anaerobic metabolism.

[Dragon-tiger fighting needling therapy in treatment of painful diabetic peripheral neuropathy: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect on painful diabetic peripheral neuropathy (PDPN) between dragon-tiger fighting needling and pregabalin capsules. METHODS: A total of 60 patients with PDPN were randomized into an observation group and a control group, 30 cases in each one. On the base of treatment with routine anti-hyperglycaemic measures and nutritional neurotherapy, the dragon-tiger fighting needling was exerted at Sanyinjiao (SP 6), Zusanli (ST 36), Yinlingquan (SP 9) and Xuehai (SP 10) in the observation group, once daily. Pregabalin capsules were prescribed for oral administration in the control group, 75 mg, twice a day. The treatment for 2 weeks was as one course and 2 courses of treatment were required in total. The score of visual analogue scale (VAS), the score of MOS item short form health survey (SF-36) and nerve conduction velocity before and after treatment were compared between the two groups. The clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, VAS score was reduced as compared with before treatment in the two groups (P<0.05). The reducing range of VAS score in the observation group was larger than the control group (P<0.05). After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of median nerve and posterior tibial nerve were all improved as compared with before treatment in the two groups (P<0.05). SNCV and MNCV in the observation group were higher than the control group (P<0.05). After treatment, the score of each item in SF-36 was increased as compared with before treatment in the two groups (P<0.05) and the score of each item in SF-36 in the observation group was higher than the control group (P<0.05). The total effective rate was 86.7% (26/30) in the observation group, better than 60.0% (18/30) in the control group (P<0.05). CONCLUSION: The dragon-tiger fighting needling therapy relieves painful symptoms, improves the quality of life and increases nerve conduction velocity in the patients with diabetic peripheral neuropathy, and the therapeutic effect is better than oral administration of pregabalin capsules.

Effects of the integration of mixed-cropping and rice-duck co-culture on rice yield and soil nutrients in southern China.

BACKGROUND: Biodiversity-based agricultural systems can improve production efficiency and sustainability, with fewer negative environmental impacts and lower use of external inputs. Mixed-cropping and rice-duck co-culture have been shown to produce ecological benefits and to have positive effects on paddy soil. However, the effects of a combination of mixed cropping with different rice cultivars and duck co-culture on soil nutrients availability and grain yields have not been evaluated. A paddy field experiment was carried out over two rice growing seasons to test these effects. RESULTS: Several combinations of rice cultivars, when integrated with duck co-culture, significantly increased the soil organic matter and total nitrogen contents during the rice growing seasons, as compared to mono-cropping systems. In mixed-cropping combined with duck co-culture (MCDC) systems, the soil alkali-hydrolyzable nitrogen content ranged from 4.33% to 17.86% higher than that in mono-cropping systems. Similar increases were found for soil available phosphorus (8.71-15.91%) and soil available potassium (8.65-39.43%) contents. Furthermore, MCDC produced higher grain yields and harvest indexes for both study seasons. CONCLUSION: The integration of MCDC systems had positive effects on soil nutrient contents of paddy fields, which could, in turn, lead to yield enhancements, as well as additional income for farmers in the form of organic duck meat. © 2019 Society of Chemical Industry.

Origin identification of Chinese Maca using electronic nose coupled with GC-MS.

Maca (Lepidium meyenii Walp.), originated in the high Andes of Peru, is rich in nutrients and phytochemicals. As a new resource food in China, Maca suffers marketing disorders due to the limitation of basic research. Due to the close relationship of Maca quality and origin of place, it's of scientific, economic and social importance to set up a rapid, reliable and efficient method to identify Maca origin. In the present study, 303 Maca samples were collected from 101 villages of the main producing area in China. Using electronic nose and BP neutral network algorithm, a Maca odor database was set up to trace the origin. GC-MS was then employed to analyze the characteristic components qualitatively and semi-quantitatively. As a result, very significant differences (p < 0.01) were detected in the volatile components of Maca from different areas. This study not only constructs a network model to forecast the Maca origin, but also reveals the relationship between Maca odor fingerprints and origins.

Mikania Micrantha Wilt Virus Alters Insect Vector's Host Preference to Enhance Its Own Spread.

As an invasive weed, Mikaniamicrantha Kunth has caused serious damage to natural forest ecosystems in South China in recent years. Mikania micrantha wilt virus (MMWV), an isolate of the Gentian mosaic virus (GeMV), is transmitted by Myzuspersicae (Sulzer) in a non-persistent manner and can effectively inhibit the growth of M. micrantha. To explore the MMWV-M. micrantha-M. persicae interaction and its impact on the invasion of M. micrantha, volatile compounds (VOCs) emitted from healthy, mock-inoculated, and MMWV-infected plants were collected, and effects on host preference of the apterous and alate aphids were assessed with Y-shaped olfactometers. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that MMWV infection changed the VOC profiles, rendering plants more attractive to aphids. Clip-cages were used to document the population growth rate of M.persicae fed on healthy, mock-inoculated, or MMWV-infected plants. Compared to those reared on healthy plants, the population growth of M. persicae drastically decreased on the MMWV-infected plants. Plant host choice tests based on visual and contact cues were also conducted using alate M.persicae. Interestingly, the initial attractiveness of MMWV-infected plants diminished, and more alate M. persicae moved to healthy plants. Taken together, MMWV appeared to be able to manipulate its plant host to first attract insect vectors to infected plants but then repel viruliferous vectors to promote its own dispersal. Its potential application for invasive weed management is discussed.

Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of "stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of "harmonizing stomach to tranquilize mind" acupuncture for insomnia and its influence on the intestinal microbiome. METHODS/DESIGN: This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups (1:1 allocation ratio). The intervention group will use "harmonizing stomach to tranquilize mind" acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment. DISCUSSION: The results of this trial are expected to confirm that "harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR1800017092.

Treatment of Uncomplicated Recurrent Urinary Tract Infection with Chinese Medicine Formula: A Randomized Controlled Trial.

OBJECTIVE: To evaluate Chinese medicine (CM) formula Bazheng Powder () as an alternative therapeutic option for female patients with recurrent urinary tract infection (RUTI). METHODS: A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula (10 herbs) for 4 weeks or antibiotics for 1 week, followed by 3 weeks of placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated. RESULTS: A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intentto- treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group (P>0.05). Bacteria were cleared from 88.5% (54/61) of patients in the CM group and 82.0% (50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1% (5/61) and 14.0 (7/61) in the CM and antibiotics groups, respectively (P>0.05). CONCLUSION: CM formula Bazheng Powder is a good alternative option for RUTI treatment. (Registration No. NCT01745328).

Multi-drug resistant uropathogenic Escherichia coli and its treatment by Chinese medicine.

OBJECTIVES: To investigate the resistance and virulence profiles of uropathogenic Escherichia coli (UPEC) and its treatment by Chinese medicine (CM) Fuzheng Qingre Lishi Formula (, FQLF). METHODS: UPEC strains were isolated from recurrent urinary tract infections (UTIs) patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs. RESULTS: A total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum ß-lactamases (ESBL)-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number (P<0.05). A mouse model was successfully constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria. CONCLUSIONS: Multi-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.

Association of green tea consumption with mortality from all-cause, cardiovascular disease and cancer in a Chinese cohort of 165,000 adult men.

Tea is the most ancient and popular beverage in the world, and its beneficial health effects has attracted tremendous attention worldwide. However, the prospective evidence relating green tea consumption to total and cause-specific mortality is still limited and inconclusive. We recruited 164,681 male participants free of pre-existing disease during 1990-1991, with green tea consumption and other covariates assessed by the standardized questionnaire and mortality follow up continued until 2006 (mean 11 years; total person-years: 1,961,791). Cox regression analyses were used to quantify the associations of green tea consumption with all-cause (n = 32,700), CVD (n = 11,839) and cancer (n = 7002) mortality, adjusting simultaneously for potential confounders. At baseline, 18 % reported regular consumption of green tea. Compared with non-green tea drinkers, regular drinkers had significantly lower all-cause mortality, with adjusted hazard ratios (HRs) being 0.94 (95 % CI 0.89, 0.99) for ≤5 g/day, 0.95 (0.91, 0.99) for 5-10 g/day and 0.89 (0.85, 0.93) for >10 g/day. For CVD mortality, the corresponding HRs were 0.93 (0.85, 1.01) 0.91 (0.85, 0.98) and 0.86 (0.79, 0.93), respectively, while for cancer they were 0.86 (0.78, 0.98), 0.92 (0.83, 1.00) and 0.79 (0.71, 0.88), respectively. The patterns of these associations varied by smoking, alcohol drinking and locality. This large prospective study shows that regular green tea consumption is associated with significantly reduced risk of death from all-cause, CVD and cancer among Chinese adults.

[Bushen Huoxue Recipe Inhibited Vascular Calcification in Chronic Renal Failure Rats by Regulating BMP-2/Runx2/Osterix Signal Pathway].

OBJECTIVE: To observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism. METHODS: Thirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot. RESULTS: HE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01). CONCLUSION: BHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.