To Explore the Mechanism of "Fuzi-Guizhi" for the Treatment of Osteoarthritis on the Basis of Network Pharmacology and Molecular Docking.

OBJECTIVE: The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform. METHODS: The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking. RESULTS: 28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP. CONCLUSION: Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.

Prophylactic Moxibustion in Preventing Postoperative Urinary Retention of Hemorrhoidectomy: A Study Protocol for a Randomized Controlled Trial.

Backgrounds: Postoperative urinary retention (POUR) is one of the most common complications after hemorrhoidectomy. The best treatment for POUR is prevention and should be involved in the whole perioperative period. Moxibustion has been used to treat urinary retention for thousands of years, and clinical studies have also proved its effects. We try to carry out a randomized, controlled, prospective study to observe whether prophylactic moxibustion could effectively reduce the incidence of POUR of hemorrhoidectomy in 24 h. Methods: This study is a single-center, evaluator-blinded, randomized, and controlled trial. Participants who meet the inclusion and exclusion criteria in this RCT will be randomly assigned to either the treatment group (moxibustion) or the control group (tamsulosin hydrochloride) in a 1:1 ratio according to a computer-generated randomization list. Both moxibustion and tamsulosin will be used 1, 10, and 24 h after operation, respectively. The outcomes of occurrence of POUR, time to first urination, catheterization rate, urinary tract infection, length of hospitalization, and adverse effects will be recorded. Discussion: The findings of the study will help to explore the preventive efficacy of prophylactic moxibustion against POUR of hemorrhoidectomy in 24 h. Trial Registration: CHiCTR, CHiCTR2000039350, registered 24 October, 2020, http://www.chictr.org.cn/showproj.aspx?proj = 63204.

[Risk Assessment Method of Non-point Source Pollution Output for Watershed Using High Resolution Data].

In recent years, non-point source pollution has become the main cause of water quality deterioration in some reservoirs in China. Taking the Panjiakou Reservoir as an example, the classical output risk model was improved by introducing a precipitation factor and terrain factor. Combined with high-resolution satellite precipitation products (GPM) and GF-6 satellite images, a high-resolution data-driven risk assessment method for non-point source pollution output was established to study the temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin. The results showed that the non-point source pollution output risk was high in the study area in 2018. The areas with higher and highest risk of nitrogen pollution output accounted for approximately 70.6% of the total watershed area, whereas the higher risk of phosphorus pollution output accounted for approximately 21.9%. The temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin were analyzed. It was found that the non-point source pollution output risk in the Panjiakou Reservoir basin increased first and then decreased from April to September. This was consistent with the spatial and temporal distribution of precipitation in the basin. Combined with the analysis of land use distribution characteristics, the upstream area of the basin was mainly cultivated land, whereas cities were concentrated in the downstream portion of the basin. Affected by agricultural production and human activities, the risk of non-point source pollution output was higher in these regions. In view of the temporal and spatial distribution characteristics of non-point source pollution output risk, it is necessary to formulate a reasonable agricultural fertilization method, plan the landscape layout of source-sinks, and construct vegetation buffer zones.

Clinical Nursing Paths Benefit Patient Outcomes Undergoing Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma.

Objective: The purpose of the study is to investigate patient outcomes of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) under clinical nursing paths (CNP) and whether the application of CNP can be a protective factor against the recurrence of HCC. Methods: The study comprised of 48 patients who received TACE for HCC under the CNP (assigned into the CNP group) and 41 who received TACE for HCC under the routine care (assigned into the control group). Their treatment safety, pain, and psychology were compared. The nursing satisfaction and quality of life were investigated when patients were discharged from the hospital. A 6-month follow-up was performed to analyze the related factors affecting disease recurrence. Results: In the CNP group, the incidence rate of total adverse reactions, VAS scores, SAS and SDA scores were lower, but conversely, the satisfaction and SF-36 scores were higher than those in the control group (P < 0.05). Logistic regression analysis revealed that advanced TNM stage, larger tumor diameter, greater Child-Pugh classification, and the presence of peripheral blood vessel invasion were independent risk factors of HCC recurrence (P < 0.05). Conclusion: The study demonstrated that CNP intervention can improve the safety and quality of life of patients undergoing TACE for HCC and reduce their negative emotions and pain feelings, which is worthy of clinical application.

Reducing the Periplasmic Glutathione Content Makes Escherichia coli Resistant to Trimethoprim and Other Antimicrobial Drugs.

Although glutathione (GSH) has been shown to influence the antimicrobial effects of many kinds of antibiotics, little is known about its role in relation to trimethoprim (TMP), a widely used antifolate. In this study, several genes related to glutathione metabolism were deleted in different Escherichia coli strains (i.e., O157:H7 and ATCC 25922), and their effects on susceptibility to TMP were tested. The results showed that deleting gshA, gshB, grxA, and cydD caused TMP resistance, and deleting cydD also caused resistance to other drugs. Meanwhile, deleting gshA, grxA, and cydD resulted in a significant decrease of the periplasmic glutathione content. Supplementing exogenous GSH or further deleting glutathione importer genes (gsiB and ggt) restored TMP sensitivity to ΔcydD. Subsequently, the results of quantitative-reverse transcription PCR experiments showed that expression levels of acrA, acrB, and tolC were significantly upregulated in both ΔgrxA and ΔcydD. Correspondingly, deleting cydD led to a decreased accumulation of TMP within bacterial cells, and further deleting acrA, acrB, or tolC restored TMP sensitivity to ΔcydD. Inactivation of CpxR and SoxS, two transcriptional factors that modulate the transcription of acrAB-tolC, restored TMP sensitivity to ΔcydD. Furthermore, mutations of gshA, gshB, grxA, cydC, and cydD are highly prevalent in E. coli clinical strains. Collectively, these data suggest that reducing the periplasmic glutathione content of E. coli leads to increased expression of acrAB-tolC with the involvement of CpxR and SoxS, ultimately causing drug resistance. To the best of our knowledge, this is the first report showing a linkage between periplasmic GSH and drug resistance in bacteria. IMPORTANCE After being used extensively for decades, trimethoprim still remains one of the key accessible antimicrobials recommended by the World Health Organization. A better understanding of the mechanisms of resistance would be beneficial for the future utilization of this drug. It has been shown that the AcrAB-TolC efflux pump is associated with trimethoprim resistance in E. coli clinical strains. In this study, we show that E. coli can sense the periplasmic glutathione content with the involvement of the CpxAR two-component system. As a result, reducing the periplasmic glutathione content leads to increased expression of acrA, acrB, and tolC via CpxR and SoxS, causing resistance to antimicrobials, including trimethoprim. Meanwhile, mutations in the genes responsible for periplasmic glutathione content maintenance are highly prevalent in E. coli clinical isolates, indicating a potential correlation of the periplasmic glutathione content and clinical antimicrobial resistance, which merits further investigation.

A functional genomics pipeline identifies pleiotropy and cross-tissue effects within obesity-associated GWAS loci.

Genome-wide association studies (GWAS) have identified many disease-associated variants, yet mechanisms underlying these associations remain unclear. To understand obesity-associated variants, we generate gene regulatory annotations in adipocytes and hypothalamic neurons across cellular differentiation stages. We then test variants in 97 obesity-associated loci using a massively parallel reporter assay and identify putatively causal variants that display cell type specific or cross-tissue enhancer-modulating properties. Integrating these variants with gene regulatory information suggests genes that underlie obesity GWAS associations. We also investigate a complex genomic interval on 16p11.2 where two independent loci exhibit megabase-range, cross-locus chromatin interactions. We demonstrate that variants within these two loci regulate a shared gene set. Together, our data support a model where GWAS loci contain variants that alter enhancer activity across tissues, potentially with temporally restricted effects, to impact the expression of multiple genes. This complex model has broad implications for ongoing efforts to understand GWAS.

Military-related posttraumatic stress disorder and mindfulness meditation: A systematic review and meta-analysis.

PURPOSE: Posttraumatic stress disorder (PTSD) is a significant global mental health concern, especially in the military. This study aims to estimate the efficacy of mindfulness meditation in the treatment of military-related PTSD, by synthesizing evidences from randomized controlled trials. METHODS: Five electronic databases (Pubmed, EBSCO Medline, Embase, PsychINFO and Cochrane Library) were searched for randomized controlled trials focusing on the treatment effect of mindfulness meditation on military-related PTSD. The selection of eligible studies was based on identical inclusion and exclusion criteria. Information about study characteristics, participant characteristics, intervention details, PTSD outcomes, as well as potential adverse effects was extracted from the included studies. Risk of bias of all the included studies was critically assessed using the Cochrane Collaboration's tool. R Statistical software was performed for data analysis. RESULTS: A total of 1902 records were initially identified and screened. After duplicates removal and title & abstract review, finally, 19 articles in English language with 1326 participants were included through strict inclusion and exclusion criteria. The results revealed that mindfulness meditation had a significantly larger effect on alleviating military-related PTSD symptoms compared with control conditions, such as treatment as usual, present-centered group therapy and PTSD health education (standardized mean difference (SMD) = -0.33; 95% CI [-0.45, -0.21]; p < 0.0001). Mindfulness interventions with different control conditions (active or non-active control, SMD = -0.33, 95% CI [-0.46, -0.19]; SMD = -0.49, 95% CI [-0.88, -0.10], respectively), formats of delivery (group-based or individual-based, SMD = -0.30, 95% CI [-0.42, -0.17], SMD = -0.49, 95% CI [-0.90, -0.08], respectively) and intervention durations (short-term or standard duration, SMD = -0.27, 95% CI [-0.46, -0.08], SMD = -0.40, 95% CI [-0.58, -0.21], respectively) were equally effective in improving military-related PTSD symptoms. CONCLUSION: Findings from this meta-analysis consolidate the efficacy and feasibility of mindfulness meditation in the treatment of military-related PTSD. Further evidence with higher quality and more rigorous design is needed in the future.

The association of vertically integrated care with health care use and outcomes.

OBJECTIVE: To determine whether vertically integrated hospital and skilled nursing facility (SNF) care is associated with more efficient use of postdischarge care and better outcomes. DATA SOURCES: Medicare provider, beneficiary, and claims data from 2012 to 2014. STUDY DESIGN: We compared facility characteristics, quality of care, and health care use for hospital-based SNFs and "virtually integrated" SNFs (defined as freestanding SNFs with close referral relationships with a single hospital) relative to nonintegrated freestanding SNFs. Among patients admitted to integrated SNFs, we estimated differences in health care use and outcomes for patients originating from the parent hospital (ie, receiving vertically integrated care) versus other hospitals using linear regressions that included SNF fixed effects. We estimated bounds for our main estimates that incorporated potential omitted variables bias. DATA EXTRACTION METHODS: We identified hospital-based SNFs based on provider data. We defined virtually integrated SNFs based on patient flows between hospitals and SNFs. We identified SNF episodes, preceding hospital stays, patient characteristics, health care use, and patient outcomes using Medicare data. PRINCIPAL FINDINGS: Consistent with prior research, integrated SNFs performed better on quality measures and health care use relative to nonintegrated SNFs (eg, hospital-based SNFs had 11-day shorter stays compared with nonintegrated SNFs adjusting for patient characteristics, P < .001). Stroke patients admitted to hospital-based SNFs from the parent hospital had shorter preceding hospital stays (adjusted difference: -1.2 days, P = .001) and shorter initial SNF stays (adjusted difference: -2.7 days, P = .049); estimates were attenuated but still robust accounting for potential omitted variables bias. For stroke patients, associations between vertically integrated care and other outcomes were either statistically insignificant or not robust to accounting for potential omitted variables bias. CONCLUSIONS: Vertically integrated hospital and SNF care was associated with shorter hospital and SNF stays. However, there were few beneficial associations with other outcomes, suggesting limited coordination benefits from vertical integration.

The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia: a meta-analysis of randomized controlled studies.

INTRODUCTION: The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia remains controversial. We conduct a systematic review and meta-analysis to explore the influence of intravenous fluid supplementation on treatment efficacy of neonatal hyperbilirubinemia. METHODS: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia. This meta-analysis is performed using the random-effect model. RESULTS: Six RCTs are included in the meta-analysis. Overall, compared with control group for neonatal hyperbilirubinemia, intravenous fluid supplementation is associated with decreased TSB at 8 h (std. MD = -0.82; 95% CI = -1.46 to -0.17; p = .01), 12 h (std. MD = -0.46; 95% CI = -0.81 to -0.10; p = .01), 24 h (std. MD = -0.47; 95% CI = -0.78 to -0.16; p = .003) and 36 h (std. MD = -0.37; 95% CI = -0.73 to -0.02; p = .04), as well as reduced incidence of exchange transfusion (RR = 0.29; 95% CI = 0.14-0.59; p = .0006), but has no significant impact on duration of phototherapy (std. MD = -0.34; 95% CI = -0.88-0.21; p = .22). CONCLUSIONS: Intravenous fluid supplementation can provide additional benefits for the treatment of neonatal hyperbilirubinemia.

MS1, a direct target of MS188, regulates the expression of key sporophytic pollen coat protein genes in Arabidopsis.

Sporophytic pollen coat proteins (sPCPs) derived from the anther tapetum are deposited into pollen wall cavities and function in pollen-stigma interactions, pollen hydration, and environmental protection. In Arabidopsis, 13 highly abundant proteins have been identified in pollen coat, including seven major glycine-rich proteins GRP14, 16, 17, 18, 19, 20, and GRP-oleosin; two caleosin-related family proteins (AT1G23240 and AT1G23250); three lipase proteins EXL4, EXL5 and EXL6, and ATA27/BGLU20. Here, we show that GRP14, 17, 18, 19, and EXL4 and EXL6 fused with green fluorescent protein (GFP) are translated in the tapetum and then accumulate in the anther locule following tapetum degeneration. The expression of these sPCPs is dependent on two essential tapetum transcription factors, MALE STERILE188 (MS188) and MALE STERILITY 1 (MS1). The majority of sPCP genes are up-regulated within 30 h after MS1 induction and could be restored by MS1 expression driven by the MS188 promoter in ms188, indicating that MS1 is sufficient to activate their expression; however, additional MS1 downstream factors appear to be required for high-level sPCP expression. Our ChIP, in vivo transactivation assay, and EMSA data indicate that MS188 directly activates MS1. Together, these results reveal a regulatory cascade whereby outer pollen wall formation is regulated by MS188 followed by synthesis of sPCPs controlled by MS1.

Utilization of healthcare services among Chinese migrants in Kenya: a qualitative study.

BACKGROUND: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. METHODS: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. RESULTS: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. CONCLUSIONS: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Identification of high-risk patients for ADR induced by traditional Chinese medicine injection: a nested case-control study.

The adverse drug reaction (ADR) of traditional Chinese medicine injection (TCMI) has become one of the major concerns of public health in China. There are significant advantages for developing methods to improve the use of TCMI in routine clinical practice. The method of predicting TCMI-induced ADR was illustrated using a nested case-control study in 123 cases and 123 controls. The partial least squares regression (PLSR) models, which mapped the influence of basic characteristics and routine examinations to ADR, were established to predict the risk of ADR. The software was devised to provide an easy-to-use tool for clinic application. The effectiveness of the method was evaluated through its application to new patients with 95.7% accuracy of cases and 91.3% accuracy of controls. By using the method, the patients at high-risk could be conveniently, efficiently and economically recognized without any extra financial burden for additional examination. This study provides a novel insight into individualized management of the patients who will use TCMI.

Huangqi Shengmai Yin Protects against Radiation-Induced Cardiac Fibrosis Injury by Regulating the TGF-ß1/Smads and MMPs.

BACKGROUND: Radiation-induced heart damage is considered to be a progressive process of fibrosis. Emerging evidence has indicated that the Smads and matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMP) may be involved in radiation-induced cardiac fibrosis (RICF) by regulating the activation of TGF-ß1 signaling pathway. Based on this, the present study was undertaken to characterize the effect of Huangqi Shengmai Yin (HSY) on RICF in a rat model. METHODS: Precardiac region of rats was irradiated with 25 Gy X-rays, and their myocardial pathology scores in terms of injury and collagen volume fraction (CVF) and the expression levels of fibrotic molecules were detected. RESULTS: The pathology scores and CVF in myocardial tissue increased after irradiation, and the expression of TGF-ß1, Col1, and Col3 increased. This change indicated that such irradiation promoted the fibrosis damage in rat hearts. The damage was accompanied by an increase in the expression of Smad 2, Smad3, Smad4, and MMP14 and a decrease in the expression of Smad 7 and TIMP1. Administration of HSY weakened the RICF by decreasing pathology score and CVF and decreased the expression of TGF-ß1, Col1, and Col3 in irradiated rat hearts. In addition, Smad2, Smad3, Smad4, and MMP14 were downregulated, while Smad 7 and TIMP1 were upregulated during intervention with HSY. CONCLUSIONS: The involvement of the TGF-ß1/Smads and MMPs/TIMP system in RICF was confirmed. This study demonstrated, for the first time, that HSY attenuates the effects of RICF in a rat model. The effect HSY was found to be closely related to the TGF-ß1/Smads signaling pathway and MMPs system. These results suggest that HSY is a prospective drug for clinical treatment of RICF.

Assessment of heavy metals, fungicide quintozene and its hazardous impurity residues in medical Panax notoginseng (Burk) F.H.Chen root.

A quick, easy, cheap, effective, rugged, and safe extraction approach and gas chromatography/tandem mass spectrometry with programmed temperature vaporization sampling technology were used to determine fungicide quintozene and its hazardous impurity hexachlorobenzene (HCB) in Panax notoginseng root, which is commonly used as a rare traditional Chinese medicine worldwide. The mean recoveries were in the ranges of 94-125 and 84-119% for quintozene and HCB with relative standard deviations of 6.2-16.1% at three concentrations: 0.01, 0.1 and 1 mg kg-1 . Heavy metals arsenic, cadmium, copper and lead were simultaneously detected by an inductively coupled plasma-mass spectrometry approach after digestion with nitric acid. The above methods were used to analyze 50 samples of P. notoginseng roots collected at markets and planting bases from the special local producing areas, namely, Honghe, Kunming and Wenshan in Yunnan province, China. Quintozene and HCB in root samples were determined at <0.0015-1.50 and <0.0015-0.125 mg kg-1 . In the 50 samples, 60, 16, 56, 2 and 6% exceeded the maximum permissible levels in medicinal plants (WM/T2-2004) for quintozene, arsenic, cadmium, lead and copper. The results showed that the method is robust and suitable for measuring quintozene, its hazardous impurity and heavy metals in P. notoginseng roots.

Insights into the microbial diversity and community dynamics of Chinese traditional fermented foods from using high-throughput sequencing approaches.

Chinese traditional fermented foods have a very long history dating back thousands of years and have become an indispensable part of Chinese dietary culture. A plethora of research has been conducted to unravel the composition and dynamics of microbial consortia associated with Chinese traditional fermented foods using culture-dependent as well as culture-independent methods, like different high-throughput sequencing (HTS) techniques. These HTS techniques enable us to understand the relationship between a food product and its microbes to a greater extent than ever before. Considering the importance of Chinese traditional fermented products, the objective of this paper is to review the diversity and dynamics of microbiota in Chinese traditional fermented foods revealed by HTS approaches.

Deletion of nudB Causes Increased Susceptibility to Antifolates in Escherichia coli and Salmonella enterica.

Co-trimoxazole, a fixed-dose combination of sulfamethoxazole (SMX) and trimethoprim (TMP), has been used for the treatment of bacterial infections since the 1960s. Since it has long been assumed that the synergistic effects between SMX and TMP are the consequence of targeting 2 different enzymes of bacterial folate biosynthesis, 2 genes (pabB and nudB) involved in the folate biosynthesis of Escherichia coli were deleted, and their effects on the susceptibility to antifolates were tested. The results showed that the deletion of nudB resulted in a lag of growth in minimal medium and increased susceptibility to both SMX and TMP. Moreover, deletion of nudB also greatly enhanced the bactericidal effect of TMP. To elucidate the mechanism of how the deletion of nudB affects the bacterial growth and susceptibility to antifolates, 7,8-dihydroneopterin and 7,8-dihydropteroate were supplemented into the growth medium. Although those metabolites could restore bacterial growth, they had no effect on susceptibilities to the antifolates. Reverse mutants of the nudB deletion strain were isolated to further study the mechanism of how the deletion of nudB affects susceptibility to antifolates. Targeted sequencing and subsequent genetic studies revealed that the disruption of the tetrahydromonapterin biosynthesis pathway could reverse the phenotype caused by the nudB deletion. Meanwhile, overexpression of folM could also lead to increased susceptibility to both SMX and TMP. These data suggested that the deletion of nudB resulted in the excess production of tetrahydromonapterin, which then caused the increased susceptibility to antifolates. In addition, we found that the deletion of nudB also resulted in increased susceptibility to both SMX and TMP in Salmonella enterica Since dihydroneopterin triphosphate hydrolase is an important component of bacterial folate biosynthesis and the tetrahydromonapterin biosynthesis pathway also exists in a variety of bacteria, it will be interesting to design new compounds targeting dihydroneopterin triphosphate hydrolase, which may inhibit bacterial growth and simultaneously potentiate the antimicrobial activities of antifolates targeting other components of folate biosynthesis.

Baicalin extracted from Huangqin (Radix Scutellariae Baicalensis) induces apoptosis in gastric cancer cells by regulating B cell lymphoma (Bcl-2)/Bcl-2-associated X protein and activating caspase-3 and caspase-9.

OBJECTIVE: To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of action. METHODS: Cell proliferation and apoptosis assays were performed to investigate the anti-proliferation effects of baicalin in human gastric cancer BGC-823 and MGC-803 cells. Real time-quantitative polymerase chain reaction and Western blotting analysis were performed to elucidate the molecular mechanisms underlying the anti-tumor properties of baicalin. RESULTS: In BGC-823 and MGC-803 gastric cancer cells treated with 80, 120, and 160 µmol/L baicalin for 48 h, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed that baicalin significantly inhibited cell proliferation in a dose-dependent manner, while flow cytometric analysis demonstrated that baicalin could induce apoptosis, also in a dose-dependent manner. Moreover, baicalin up-regulated the expression of caspase-3, caspase-9, and B cell lymphoma (Bcl-2)-associated X protein and down-regulated the expression of Bcl-2 at both the mRNA and protein level. CONCLUSION: Baicalin has potential as a therapeutic agent for gastric cancer by inducing apoptosis in cancer cells.

A survey of evidence users about the information need of acupuncture clinical evidence.

BACKGROUND: The PRISMA statement was rarely used in the field of acupuncture, possibly because of knowledge gaps and the lack of items tailored for characteristics of acupuncture. And with an increasing number of systematic reviews in acupuncture, it is necessary to develop an extension of PRISMA for acupuncture. And this study was the first step of our project, of which the aim was to investigate the need for information of clinical evidence on acupuncture from the perspectives of evidence users. METHODS: We designed a questionnaire based on a pilot survey and a literature review of acupuncture systematic review or meta-analysis(SR/MA). Participants from five cities (Lanzhou, Chengdu, Shanghai, Nanjing and Beijing) representing the different regions of China, including clinicians, researchers and postgraduates in their second year of Master studies or higher level, were surveyed. RESULTS: A total of 269 questionnaires were collected in 18 hospitals, medical universities and research agencies, and 251 (93 %) with complete data were used for analysis. The average age of respondents was 33 years (SD 8.959, range 25-58) with male 43 % and female 57 %. Most respondents had less than 5 years of working experience on acupuncture, and read only one to five articles per month. Electronic databases, search engines and academic conferences were the most common sources for obtaining information. Fifty-six percent of the respondents expressed low satisfaction of the completeness of information from the literature. The eight items proposed for acupuncture SR/MAs received all high scores, and five of the items scored higher than eight on a scale zero to ten. The differences for the scores of most items between postgraduates and non-postgraduates were not statistically significant. CONCLUSIONS: The majority of the respondents were not very satisfied with the information provided in acupuncture SRs. Most of the items proposed in this questionnaire received high scores, and opinions from postgraduates and non-postgraduates tended to agree on most items. Comments from the respondents can promote future work.

The transcription factors MS188 and AMS form a complex to activate the expression of CYP703A2 for sporopollenin biosynthesis in Arabidopsis thaliana.

The sexine layer of pollen grain is mainly composed of sporopollenins. The sporophytic secretory tapetum is required for the biosynthesis of sporopollenin. Although several enzymes involved in sporopollenin biosynthesis have been reported, the regulatory mechanism of these enzymes in tapetal layer remains elusive. ABORTED MICROSPORES (AMS) and MALE STERILE 188/MYB103/MYB80 (MS188/MYB103/MYB80) are two tapetal cell-specific transcription factors required for pollen wall formation. AMS functions upstream of MS188. Here we report that AMS and MS188 target the CYP703A2 gene, which is involved in sporopollenin biosynthesis. We found that AMS and MS188 were localized in tapetum while CYP703A2 was localized in both tapetum and locule. Chromatin immunoprecipitation (ChIP) showed that MS188 directly bound to the promoter of CYP703A2 and luciferase-inducible assay showed that MS188 activated the expression of CYP703A2. Yeast two-hybrid and electrophoretic mobility shift assays (EMSAs) further demonstrated that MS188 complexed with AMS. The expression of CYP703A2 could be partially restored by the elevated levels of MS188 in the ams mutant. Therefore, our data reveal that MS188 coordinates with AMS to activate CYP703A2 in sporopollenin biosynthesis of plant tapetum.

Novel naphtho[2,1-d]oxazole-4,5-diones as NQO1 substrates with improved aqueous solubility: Design, synthesis, and in vivo antitumor evaluation.

A new series of ortho-naphthoquinone analogs of ß-lapachone were designed, synthesized and evaluated. The biological results indicated that most of our compounds were efficient substrates for NQO1. The new scaffold with water-soluble side chain resulted in greater solubility under acidic condition compared to ß-lapachone. Thus avoiding the use of hydroxylpropyl ß-cyclodextrin which would finally cause the rapid drug clearance from the blood and dose-limiting toxicity in the form of hemolytic anemia. The most soluble and promising compound in this series was 2-((4-benzylpiperazin-1-yl)methyl)naphtho[2,1-d]oxazole-4,5-dione (3k), which inhibited cancer cell (NQO1-rich A549 cell line) growth at IC50 values of 4.6±1.0µmol·L(-1). Furthermore, compound 3k had in vivo antitumor activity in an A549 tumor xenografts mouse model comparable to the activity obtained with ß-lapachone. The results indicated that these ortho-naphthoquinones could serve as promising leads for further optimization as novel substrates for NQO1.