Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation.

Callicarpa nudiflora is a traditional folk medicine in China used for eliminating stasis to subdue swelling. Several compounds from Callicarpa nudiflora have been proved to show anti-inflammatory, haemostasis, hepatitis, and anti-proliferative effects. Tumor endothelial cells play crucial roles in tumor-induced angiogenesis. Recently, it was demonstrated that ECs may be the important source of cancer associated fibroblasts (CAFs) through endothelial to mesenchymal transition (EndoMT). In this study, we evaluated the effects of nudifloside (NDF), a secoiridoid glucoside from Callicarpa Nudiflora, on TGF-ß1-induced EndoMT and VEGF-induced angiogenesis, and the underlying mechanisms were also involved. It was found that NDF significantly inhibited enhanced migration, invasion and F-actin assembly in endothelial cells (ECs) exposed in TGF-ß1. NDF obviously reversed expression of several biomarkers associated with EndoMT and recovered the morphological characteristics of ECs and tube-like structure induced by TGF-ß1. Furthermore, treatment of NDF resulted in a significant destruction of VEGF-induced angiogenesis in vitro and ex vivo. Data from co-immunoprecipitation assay provided the evidence that Ezrin phosphorylation and the interaction with binding protein can be inhibited by NDF, which can be confirmed by data from Ezrin silencing assay. Collectively, the application of NDF inhibited TGF-ß1-induced EndoMT and VEGF-induced angiogenesis in ECs by reducing Ezrin phosphorylation.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

Implementation of normal childbirth guidelines among midwives: Adherence and influencing factors.

BACKGROUND: Clinical practice guidelines on normal childbirth were issued worldwide with a view to achieve evidence-based, cost-effective and universal intrapartum care. Effective implementation of guideline recommendations is impossible without a full evaluation and understanding of current practice and factors influencing adherence among midwives. AIM: This study aimed to explore midwives' adherence to clinical practice guidelines on normal childbirth and factors influencing the implementation of guideline recommendations in mainland China. DESIGN: We used a mixed-method sequential explanatory design. METHODS: A national level cross-sectional survey was conducted among 718 midwives to investigate their adherence to guideline recommendations on normal childbirth. Based on the findings of quantitative study phase, we developed the interview outline and performed semi-structured interviews with thirteen midwives to explore potential factors influencing their implementation of normal childbirth guidelines. An inductive thematic analysis was undertaken to identify themes, which were then deductively mapped to the Theoretical Domains Framework (TDF). RESULTS: Midwives' adherence to the guideline recommendations was relatively low, with non-adherence to thirteen guideline recommendations (41.94%) being observed. Six domains on the TDF and one additional theme were found to be factors influencing midwives' implementation of guideline recommendations on normal childbirth, with behavioural regulation, beliefs about consequences, professional roles and responsibilities being identified as barriers for interventions recommended against use, knowledge, environmental context and resources being identified as enablers for interventions recommended for use, and skills and women's preference being identified as barriers/enabler for both. CONCLUSION: Guideline adherence can be improved by multifaceted efforts at professional, organizational and maternal levels. The identification of barriers and enablers of guideline implementation provides a solid foundation for further reducing non-evidence-based intrapartum interventions.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis.

BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

The management framework of upright position in the second stage of labour: A qualitative study.

BACKGROUND: Upright positions, as a non-pharmacological, have been well documented in multiple studies to promote normal labor, facilitate favourable birth outcomes and positive childbirth experience. Yet, the application status of upright positions in China, and even globally, is unfavourable. Thus, we have developed the Program for Upright Positions in the Second Stage of Labor (UPSSL program) for the widespread application of upright positions. While there is limited research evidence on the areas of improvement and corresponding strategies for embedding the evidence into midwifery practice. OBJECTIVES: To explore perspectives of health care providers on improvement areas of upright positions in the second stage of labor, and to identify corresponding strategies in order to develop a management framework for successful implementation of upright positions. METHODS: A qualitative descriptive design with semi-structured interviews was conducted in the study. The participants involving 13 midwives, six obstetricians and six department managers were selected from three hospitals in Beijing, China. ATLAS.TI 8 software was utilized to manage, identify the transcript data, and the thematic analysis method guided the data analysis. RESULTS: A management framework of upright positions in the second stage of labor was developed based on our study, which included five improvement areas : (1) promoting the renewal of midwifery notions and the professional training;(2) strengthening maternal health education based on the "trinity" approach; (3) promoting multidisciplinary cooperation and refining the labor procedures in upright positions; (4) optimizing midwifery human resource allocation and formulating incentive policies; (5) encouraging partner involvement and improving the birth environment. CONCLUSIONS: The study findings could provide a comprehensive view to promote UPSSL Program to be utilized in practice. Our study also provided a way for midwives, obstetricians, and other healthcare providers to work together to facilitate high quality maternal care. IMPLICATIONS FOR PRACTICE: Our findings will be useful for nursing managers to carry out the UPSSL program through several strategies, such as strengthening the professional training for assisting labor in the upright positions, reallocating midwifery human resources, and developing the childbirth education on the upright positions.

Network pharmacology and molecular docking reveal the mechanism of Qinghua Xiaoyong Formula in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory illness of the digestive system with unknown etiology, and its incidence is increasing worldwide. However, there are currently no effective treatments or medications available for individuals with CD. Therefore, novel therapeutic strategies are urgently needed. The bioactive compounds and targets associated with compounds of Qinghua Xiaoyong Formula (QHXYF) were examined using The Traditional Chinese Medicine Systems Pharmacology database, and 5 disease target databases were also used to identify CD-related disease targets. A total of 166 overlapping targets were identified from QHXYF-related and CD-related disease targets and they were found to be enriched in oxidative stress-related pathways and the PI3K/AKT signaling pathway. Molecular docking was then used to predict how the bioactive compounds would bind to the hub targets. It was found that quercetin could be the core bioactive compound and had good binding affinity to the top 5 hub targets. Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF ß1/Smad3 and NF-κB signaling pathways.

BACKGROUND: Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment. AIM: To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1. METHODS: Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-ß1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFß1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student's t test. RESULTS: NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFß1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFß1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1. CONCLUSION: Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.

Determination of 44 major components and chemical profiling of saccharide in Chinese medicinal formula Lanqin Oral Liquid.

INTRODUCTION: Lanqin Oral Liquid (LQL) is a traditional Chinese medicine preparation (TCMP) containing five herbal medicines and has been commonly used for the treatment of pharyngitis and hand-foot-and-mouth disease in clinic. The material basis of LQL has been reported in our previous study, but the contents of the major components and the features of saccharide in LQL are still unclear. OBJECTIVES: This study aimed to establish accurate and rapid methods for the quantification of the major components and profiling of saccharide in LQL. The quantitative results combined with similarity evaluation were applied to improve the quality control of LQL. METHODOLOGY: An ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS) method was utilised to determine 44 major components. Cosine similarity was used to evaluate the similarities among 20 batches of LQL based on the quantitative results of 44 major components. The physicochemical properties, structure, composition, and contents of saccharide in LQL were detected by a combination of chemical and instrumental analysis. RESULTS: A total of 44 compounds, including flavonoids, iridoid glycosides, alkaloids, and nucleosides, were accurately determined. The 20 batches of LQL were remarkably similar (> 0.95). In addition, d-glucose, galactose, d-glucuronic acid, arabinose, and d-mannose were detected in saccharide of LQL. The contents of saccharide in LQL were 13.52-21.09 mg/ml. CONCLUSIONS: The established methods can be applied for the comprehensive quality control of LQL, including characterisation of saccharide and quantification of representative components. Our study will provide a robust chemical foundation for disclosing the quality markers of its therapeutic effect.

A randomized superiority clinical trial: metronidazole improved the efficacy of high-dose dual therapy in Helicobacter pylori rescue treatment.

BACKGROUND AND OBJECTIVES: High-dose dual therapy [proton pump inhibitor (PPI) + amoxicillin] is recommended as a Helicobacter pylori rescue treatment. However, its efficacy is still controversial. The aim of this study was to evaluate the efficacy and safety of triple therapy containing high dose of PPI and amoxicillin plus metronidazole compared with dual therapy in rescue treatment. METHODS: Two hundred and sixty-eight patients who failed at least two courses of H. pylori treatment were recruited and randomly allocated into two 14-day groups: esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily plus metronidazole 400 mg three times daily (EAM group); or esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily (EA group). The agar-dilution method was performed as an antibiotic susceptibility test. The 13C urea breath test was used to assess H. pylori eradication at 6 weeks after the treatment. The study was registered at clinicaltrials.gov (NCT04024527). RESULTS: H. pylori eradication rates in the EAM group were 85.8% (115/134, 95% CI 79.9%-91.7%) in ITT analysis and 92.6% (113/122, 95% CI 87.9%-97.3%) in PP analysis, significantly higher than those of the EA group, which were 73.1% (98/134, 95% CI 65.6%-80.6%) and 83.1% (98/118, 95% CI 76.8%-89.8%) (P = 0.005, 0.011). Resistance rates of amoxicillin and metronidazole were 6.6% (13/196) and 89.8% (176/196). Metronidazole resistance did not affect the eradication rates in the EAM group. Both groups had similar moderate and severe adverse events and similar compliance. CONCLUSIONS: A triple therapy containing high dose of PPI and amoxicillin plus metronidazole could be a potential rescue therapy worldwide even in a high metronidazole-resistance region.

Effects of perineal massage during childbirth on maternal and neonatal outcomes in primiparous women: A systematic review and meta-analysis.

BACKGROUND: Perineal massage during childbirth has been recommended as an effective measure to prevent perineal injury. However, the overall effects of perineal massage during childbirth on maternal and neonatal outcomes in primiparous women remain inconclusive. Particularly, the effects of perineal massage begun during different stages of labor need to be further investigated. OBJECTIVES: To comprehensively review the effects of perineal massage during childbirth on primiparous health outcomes, including perineal-related outcomes, duration of labor, hemorrhage and postpartum perineal pain, and neonatal outcomes, including Apgar scores and neonatal complications, and to further explore the effects of perineal massage begun during different stages of labor. DESIGN: A systematic review and meta-analysis following the Cochrane Handbook guidelines and PRISMA2020. METHODS: A systematic search strategy was developed following the three-phase search approach, and the literature search was conducted in electronic databases and clinical trial registers from inception to 7th January 2022. Study selection and data extraction were completed independently by two researchers. The updated Cochrane risk of bias 2.0 tool for randomized trials was chosen to evaluate the quality of included studies. Data analyses were conducted using the Revman5.4 software, and subgroup analyses were performed based on the different start times of perineal massage. Furthermore, the certainty of body of evidence for each outcome was assessed utilizing the GRADEpro online tool. RESULTS: Seventeen randomized controlled trials involving 3248 primiparous women were included in the review. The pooled results of meta-analyses indicated that perineal massage begun during the second stage of labor significantly increased the occurrence of intact perineum (RR = 2.78, 95 % CI: [1.52, 5.05], P < 0.001), reduced the rate of second- and third-degree perineal lacerations (P < 0.05), and decreased the incidence of episiotomy (RR = 0.63, 95 % CI: [0.50, 0.79], P < 0.001), while perineal massage during the first stage of labor effectively shortened the duration of the first and second stages of labor (P < 0.05). The available evidence also suggests the potential role of perineal massage on hemorrhage and long-term postpartum perineal pain (P < 0.05). However, the aggregated results failed to demonstrate the beneficial effects of perineal massage on neonatal outcomes (P > 0.05). CONCLUSIONS: Perineal massage begun during the second stage of labor effectively improves the perineal-related outcomes in primiparous women, while perineal massage during the first stage of labor significantly shortens the duration of labor. High-quality studies exploring the standardized procedure for perineal massage and the short- and long-term effects of perineal massage are warranted. REGISTRATION NUMBER: CRD42022302336 (PROSPERO).

Effects of different techniques during the second stage of labour on reducing perineal laceration: An overview of systematic reviews.

AIM AND OBJECTIVE: To summarize the evidence on the effects of different techniques during the second stage of labour on reducing perineal laceration depending on available systematic reviews to provide optimal evidence for decision-making. BACKGROUND: Preventing perineal laceration has been considered an important part of improving women's health. Various techniques have been used to prevent perineal laceration during the second stage of labour. However, systematic reviews evaluating the effects of different techniques on reducing perineal laceration show inconsistent results. DESIGN: Overview of systematic reviews. METHODS: Five English and four Chinese databases were systematically searched for relevant systematic reviews and meta-analyses published between 1 January 2016 and 31 August 2021. The quality of the included reviews was assessed by the AMSTAR 2 tool. A narrative synthesis was conducted to report the results of moderate-to-high quality systematic reviews. The overview was reported according to the PRISMA statement. RESULTS: Eighteen reviews were included, of which four reviews had moderate-to-high methodological quality. Perineal massage and warm compresses significantly decreased the incidence of third- or fourth-degree perineal laceration (moderate-quality evidence). Hands-off technique had no impact on perineal laceration (low-to-moderate quality evidence). Ritgen's manoeuvre could reduce the incidence of first-degree perineal laceration but increase the incidence of second-degree perineal laceration (very low-quality evidence). Spontaneous pushing (low-quality evidence) and delayed pushing (moderate-quality evidence) had no impact on the incidence of third- or fourth-degree perineal laceration. Upright positions did not increase the risk of third- or fourth-degree perineal laceration (very low- to low-quality evidence) but increased the risk of second-degree perineal laceration for women without epidural analgesia (low-quality evidence). CONCLUSIONS: Perineal massage and warm compresses could be the better choice for preventing perineal laceration in the second stage of labour. RELEVANCE TO CLINICAL PRACTICE: Midwives and obstetricians could use perineal massage and warm compresses to prevent perineal laceration and should consider women's preferences and experience with perineal techniques.

Molecular mechanisms and genetic improvement of low-phosphorus tolerance in rice.

Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil, making it unavailable to plants. Limited phosphate rock resources, low phosphate fertilizer use efficiency and high demands for green agriculture production make it important to clarify the molecular mechanisms underlying plant responses to P deficiency and to improve plant phosphate efficiency in crops. Over the past 20 years, tremendous progress has been made in understanding the regulatory mechanisms of the plant P starvation response. Here, we systematically review current research on the mechanisms of Pi acquisition, transport and distribution from the rhizosphere to the shoot; Pi redistribution and reuse during reproductive growth; and the molecular mechanisms of arbuscular mycorrhizal symbiosis in rice (Oryza sativa L.) under Pi deficiency. Furthermore, we discuss several strategies for boosting P utilization efficiency and yield in rice.

[Application regularity and solution strategies of mineral medicine Cinnabaris in pediatric preparations].

Mineral medicine is a characteristic element of advantage of traditional Chinese medicine(TCM), which embodies unique scientific connotation. Cinnabaris is a characteristic drug in Chinese medicinal preparations, especially in Chinese medicinal pediatric preparations. Because of the adverse reactions caused by mercury contained, the safety and application of Cinnabaris have attracted much attention. To explore the application regularity and the value of the pediatric preparations containing Cinnabaris, this study statistically analyzed 32 Cinnabaris-contained pediatric preparations in the 2020 edition of the Chinese Pharmacopoeia and 105 pediatric preparations containing Cinnabaris in the Dictionary of Traditional Chinese Medicine Prescriptions(Vol. Ⅰ and Ⅱ). The statistical results indicated that the pediatric preparations and formulae containing Cinnabaris had great advantages in the treatment of pediatric convulsions, but there were still problems in dosage form, dosage, and quality control. In this study, ICP-MS and LC-AFS were further used to determine the content of total mercury and soluble mercury in 15 commercially available pediatric preparations containing Cinnabaris. It was found that the total mercury content was far higher than soluble mercury content in the sample preparations, and there was no obvious correlation between them. According to the results, the research and application strategies of Cinnabaris were put forward in order to provide references for the rational application of Cinnabaris in pediatric preparations.

2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment.

BACKGROUND: Helicobacter pylori ( H. pylori ) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection. METHODS: This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS: Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy. CONCLUSIONS: The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders' values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges. REGISTRATION: Guidelines International Network (GIN) website, https://guidelines.ebmportal.com/node/69996 .

Barriers and facilitators to the implementation of a practice programme for upright positions in the second stage of labour in China: A qualitative study.

OBJECTIVE: Upright positions in the second stage of labour are recommended by many labour and birth guidelines, but they have not been widely used in China and the implementation varies greatly. Given this, we developed a Practice Programme for Upright Positions in the Second Stage of Labour (UPSSL Programme). Whether the UPSSL Programme can be translated into action in the local context is a crucial issue that needs to be further explored. This study aimed to explore barriers and facilitators to the implementation of the UPSSL Programme in the Chinese context to facilitate the integration of evidence and routine clinical practice. DESIGN: A descriptive qualitative design was adopted. SETTING: The study was conducted in the maternity unit of a tertiary general hospital in China. PARTICIPANTS: A purposeful sampling was used to recruit midwives, obstetricians and their leaders. Data were collected through semi-structured face-to-face interviews. The Consolidated Framework for Implementation Research was used to guide the development of interview guide and the analysis of qualitative data. The study was reported following the Standards for Reporting Qualitative Research. FINDINGS: Twelve eligible participants were interviewed, including eight midwives, two obstetricians, the head nurse of the delivery room, and the head of the maternity unit. Eight barriers and 10 facilitators were identified by using the directed content analysis. The barriers to implementing the UPSSL Programme were professionals' concerns about the potential risks of the programme (relative advantage), higher complexity (complexity), placement method of upright positions presented without pictures (design quality & packaging), staff shortage (cost), limited understanding of parturients' needs (patient needs & resources), lack of a training protocol for professionals (available resources), professionals' limited knowledge and skills in the programme (knowledge & beliefs about the intervention), and lack of confidence in the successful implementation of the programme (self-efficacy). KEY CONCLUSIONS: Participants expressed several barriers and facilitators to implementing the UPSSL Programme in clinical practice in the Chinese context. IMPLICATIONS FOR PRACTICE: The findings provide a reference for the development of targeted implementation strategies that could promote the integration of evidence and routine clinical practice, and thus facilitate the normative application and promotion of upright positions in China.

Study on inhibition of Britannin on triple-negative breast carcinoma through degrading ZEB1 proteins.

BACKGROUND: Triple-negative breast carcinomas (TNBCs) are a breast carcinoma with the most aggressive form, which is demonstrated as enhanced invasion and recurrence. Britannin is extracted mainly from the traditional Chinese herb Inula japonica Thunb, and few studies have focused on its effect on TNBC. Moreover, there is still no report concerning the role of Britannin in degrading the transcripts of Zinc finger E-box-binding homeobox 1 (ZEB1) proteins. PURPOSE: To explore the potential effect of Britannin on invasion and stemness of TNBCs and its underlying mechanism. METHODS: Cellular activity was measured using MTT, and cell cycle was measured using flow cytometry (FCM). The effect of Britannin on the migrating and invading abilities of MDA-MB-231 and 4T1 cells were measured using the wound healing and transwell assays. The sizes and number of breast carcinoma cells were measured by tumor formation assay and in vitro limiting-dilution assay. CD44 expression in tumor spheroids was tested by immunofluorescence assay. Nextly, the expressions of epithelial-mesenchymal transition (EMT) markers and ZEB1 protein expressional level were detected by western blot . ZEB1 mRNA expressional level was analyzed using RT-qPCR. Drug affinity-responsive target stability (DARTS) method was used to detect the binding activity between Britannin and ZEB1. Co-immunoprecipitation (Co-IP) analysis was applied to test the ubiquitination of ZEB1. The mouse models for experimental lung metastasis of 4T1 cells were established to detect the anti-metastasis effect of Britannin in vivo, and the expressional levels of EMT markers in lung metastases were detected by immunohistochemistry. RESULTS: Britannin could inhibit cell growth and G2/M arrest in TNBC cells. Britannin could inhibit the migrating and invading ability without inducing severe apoptosis of MDA-MB-231 and 4T1 cells. Meanwhile, Britannin reduced the size and number of spheroids formed in these two cells, and decreased the expressional level of stem cells biomarker CD44 in tumor spheroids. Mechanism research showed that Britannin specifically bound to ZEB1 and induced its ubiquitination in MDA-MB-231 cells. Afterwards, Britannin disturbed protein stability and promoted ZEB1 protein degradation. Importantly, Britannin could not inhibit cell invasion and spheroid formation after ZEB1 expression was knocked down. Finally, Britannin inhibition of 4T1 cell metastasis was confirmed through establishing mouse models for the experimental lung metastasis. It was proved that both Britannin and paclitaxel could decrease the lung metastases, and Britannin could also down-regulate the protein expressional levels of ZEB1, MMP9 and CD44. CONCLUSION: This study reveals that Britannin suppresses the invasion and metastasis of TNBC cells through degrading ZEB1, which suggests that Britannin can be used to prevent tumor metastasis and recurrence via degrading ZEB1proteins.

Potential mechanisms of Pyrrosiae Folium in treating prostate cancer based on network pharmacology and molecular docking.

OBJECTIVE: The network pharmacology approach and molecular docking were employed to explore the mechanism of Pyrrosiae Folium (PF) against prostate cancer (PCa). METHODS: The active compounds and their corresponding putative targets of PF were identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP), the gene names of the targets were obtained from the UniProt database. The collection of genes associated with PCa was obtained from GeneCards and DisGeNET database. We merged the drug targets and disease targets by online software, Draw Venn Diagram. The resulting gene list was imported into R software (v3.6.3) for GO and KEGG function enrichment analysis. The STRING database was utilized for protein-protein interaction (PPI) network construction. The cytoHubba plugin of Cytoscape was used to identify core genes. Further, molecular docking analysis of the hub targets was carried out using AutoDock Vina software (v1.5.6). RESULTS: A total of six active components were screened by PF, with 167 corresponding putative targets, 1395 related targets for PCa, and 113 targets for drugs and diseases. The 'drug-component-disease-target' network was constructed by Cytoscape software and the target genes mainly involved in the complex treating effects associated with response to oxidative stress, cytokine activity, pathways in cancer, PCa pathway, and tumor necrosis factor (TNF) signaling pathway. Core genes in the PPI network were TNF, JUN, IL6, IL1B, CXCL8, RELA, CCL2, TP53, IL10, and FOS. The molecular docking results reveal the better binding affinity of six active components to the core targets. CONCLUSION: The results of this study indicated that PF may be have a certain anti-PCa effect by regulating related target genes, affecting pathways in cancer, TNF signaling pathway, and hepatitis B signaling pathway.