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Background: Epidemiological studies have shown that young women often suffer from primary dysmenorrhea (PD) which is a common cause that affects their routine work and quality of life. Chinese herbal medicine has been widely used for PD in China. A systematic review found that Xuefu Zhuyu (XFZY) has a promising effect on PD management, yet there is a dearth of high-quality evidence in support of this claim. We want to conduct a randomized controlled trial to evaluate the efficacy and safety of XFZY for PD patients.Methods: This is a protocol for a multicenter, randomized, placebo-controlled trial. A total of 248 participants with PD will be recruited at 6 centers and randomized into two groups-a herbal treatment group and a placebo group. The participants will receive either XFZY or placebo, three times per day, for 3 menstrual cycles, with a 12-week follow-up. The primary outcome will be the mean change in pain intensity as measured by VAS, while the change in menstrual pain duration, the change in peak pain intensity as measured by VAS, the Cox Menstrual Symptom Scale (CMSS), quality of life EQ-5D-5L, cumulative painkiller consumption, and health economics will be included as secondary outcomes. Adverse events will also be reported.Discussion: This protocol describes a multicenter, double-blind, randomized, placebo-controlled trial that investigates the efficacy and safety of XFZY for primary dysmenorrhea. Validated evaluation tools will assess dysmenorrhea severity. We believe that this research will provide important evidence regarding the use of XFZY to treat dysmenorrhea.Trial Registration: Chinese Clinical Trial Registry ChiCTR1900026819 . Registered on 23 October 2019. [ABSTRACT FROM AUTHOR]

Background: Hyperlipidemia, defined as elevated lipid levels, is the primary and major risk factor for atherosclerotic cardiovascular disease. Several studies have evaluated the effects of Chinese medicine (CM) on hyperlipidemia. However, due to the varied designs and methods of these studies, data synthesis has been difficult, restricting the practical value of the findings. Developing a core outcome set (COS) could solve these methodological concerns. In this paper, we report a protocol to develop a COS for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia).Methods: The development of COS-CM-Hyperlipidemia will include four stages: (1) a systematic review to identify potential important outcomes-a study advisory group, composed of core stakeholders of hyperlipidemia, will be set up afterwards to evaluate the identified outcomes and a candidate outcome set will be developed accordingly; (2) a panel of experts will be invited to conduct a three-round Delphi survey, so that the experts' opinions on the importance of outcomes for treating hyperlipidemia with CM will be collected; (3) a consensus meeting with clinicians, patients, and other key stakeholders will be conducted to finalize the items and definitions; and (4) COS-CM-Hyperlipidemia will be promoted and updated.Discussion: The development of this COS will improve the design and operation of CM trials on hyperlipidemia, keeping them in compliance with international standards, as well as the comparability and utility of their results.Trial Registration: The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.comet-initiative.org/studies/details/983 . Registered on 25 April 2017. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and effectiveness of endovascular treatment for massive haemoptysis caused by pulmonary pseudoaneurysm (PAP). Methods: The clinical data, imaging data, and endovascular treatment protocol of 23 patients with massive haemoptysis caused by continuous PAP were retrospectively analysed. The success, complications, postoperative recurrence rate, and influence of the treatment on pulmonary artery pressure were also evaluated. Results: Nineteen patients with a bronchial artery-pulmonary artery (BA-PA) and/or nonbronchial systemic artery-pulmonary artery (NBSA-PA) fistula underwent bronchial artery embolization (BAE) and/or nonbronchial systemic artery embolization (NBSAE) + pulmonary artery embolization (PAE). The pulmonary artery (PA) pressures before and after embolization were 52.11 ± 2.12 (35–69 cmH2O) and 33.58 ± 1.63 (22–44 cmH2O), respectively (P = 0.001). Four patients did not have a BA-PA and/or NBSA-PA fistula. Embolization was performed in two patients with a distal PAP of the pulmonalis lobar arteria. Bare stent-assisted microcoils embolization was performed in the other two patients with a PAP of the main pulmonary lobar arteries. The PA pressures of the four patients before and after treatment were 24.50 ± 1.32 (22–28 cmH2O) and 24.75 ± 1.70 (22–29 cmH2O), respectively (P = 0.850). The technique had a 100% success rate with no serious complications and a postoperative recurrence rate of 30%. Conclusion: Endovascular treatment is safe and effective for massive haemoptysis caused by PAP. BAE and/or NBSAE can effectively reduce pulmonary hypertension in patients with a BA-PA and/or NBSA-PA fistula. [ABSTRACT FROM AUTHOR]

Background: This study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions. Methods: Twenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded. Results: The LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05). Conclusion: Following treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients. [ABSTRACT FROM AUTHOR]

Background: Protein lysine 2-hydroxyisobutyrylation (Khib) is a novel post-translational modification (PTM) discovered in cells or tissues of animals, microorganisms and plants in recent years. Proteome-wide identification of Khib-modified proteins has been performed in several plant species, suggesting that Khib-modified proteins are involved in a variety of biological processes and metabolic pathways. However, the protein Khib modification in soybean, a globally important legume crop that provides the rich source of plant protein and oil, remains unclear. Results: In this study, the Khib-modified proteins in soybean leaves were identified for the first time using affinity enrichment and high-resolution mass spectrometry-based proteomic techniques, and a systematic bioinformatics analysis of these Khib-modified proteins was performed. Our results showed that a total of 4251 Khib sites in 1532 proteins were identified as overlapping in three replicates (the raw mass spectrometry data are available via ProteomeXchange with the identifier of PXD03650). These Khib-modified proteins are involved in a wide range of cellular processes, particularly enriched in biosynthesis, central carbon metabolism and photosynthesis, and are widely distributed in subcellular locations, mainly in chloroplasts, cytoplasm and nucleus. In addition, a total of 12 sequence motifs were extracted from all identified Khib peptides, and a basic amino acid residue (K), an acidic amino acid residue (E) and three aliphatic amino acid residues with small side chains (G/A/V) were found to be more preferred around the Khib site. Furthermore, 16 highly-connected clusters of Khib proteins were retrieved from the global PPI network, which suggest that Khib modifications tend to occur in proteins associated with specific functional clusters. Conclusions: These findings suggest that Khib modification is an abundant and conserved PTM in soybean and that this modification may play an important role in regulating physiological processes in soybean leaves. The Khib proteomic data obtained in this study will help to further elucidate the regulatory mechanisms of Khib modification in soybean in the future. [ABSTRACT FROM AUTHOR]

Recent years, Burkholderia species have emerged as a new source of natural products (NPs) with increasing attractions. Genome mining suggests the Burkholderia genomes include many natural product biosynthetic gene clusters (BGCs) which are new targets for drug discovery. In order to collect more Burkholderia, here, a strain S-53 was isolated from the soil samples on a mountain area in Changde, P.R. China and verified by comparative genetic analysis to belong to Burkholderia. The complete genome of Burkholderia strain S-53 is 8.2 Mbps in size with an average G + C content of 66.35%. Its taxonomy was both characterized by 16S rRNA- and whole genome-based phylogenetic trees. Bioinformatic prediction in silico revealed it has a total of 15 NP BGCs, some of which may encode unknown products. It is expectable that availability of these BGCs will speed up the identification of new secondary metabolites from Burkholderia and help us understand how sophisticated BGC regulation works. [ABSTRACT FROM AUTHOR]

Background: The ideal neural interface or scaffold for stem cell therapy shall have good biocompatibility promoting survival, maturation and integration of neural stem cells (NSCs) in targeted brain regions. The unique electrical, hydrophilic and surface-modifiable properties of Ti3C2Tx MXene make it an attractive substrate, but little is known about how it interacts with NSCs during development and maturation. Results: In this study, we cultured NSCs on Ti3C2Tx MXene and examined its effects on morphological and electrophysiological properties of NSC-derived neurons. With a combination of immunostaining and patch-clamp recording, we found that Ti3C2Tx MXene promotes NSCs differentiation and neurite growth, increases voltage-gated current of Ca2+ but not Na+ or K+ in matured neurons, boosts their spiking without changing their passive membrane properties, and enhances synaptic transmission between them. Conclusions: These results expand our understanding of interaction between Ti3C2Tx MXene and NSCs and provide a critical line of evidence for using Ti3C2Tx MXene in neural interface or scaffold in stem cell therapy. [ABSTRACT FROM AUTHOR]

Background: The longer upper airway is more collapsible during sleep. This study aims to reveal relationships among upper airway length, weight, and obstructive sleep apnea (OSA), particularly to answer why the upper airway of OSA patients is longer than that of healthy people and why some obese people suffer from OSA while others do not.Methods: We perform head and neck MRI on male patients and controls, and measure > 20 morphological parameters, including several never before investigated, to quantify the effect of weight change on upper airway length.Results: The upper airway length is longer in patients and correlates strongly to body weight. Weight increase leads to significant fat infiltration in the tongue, causing the hyoid to move downward and lengthen the airway in patients. The apnea-hypopnea index (AHI) strongly correlates to airway length and tongue size. Surprisingly, a distance parameter h and angle β near the occipital bone both show significant differences between healthy males and patients due to their different head backward tilt angle, and strongly correlates with AHI. The contributions of downward hyoid movement and head tilt on airway lengthening are 67.4-80.5% and19.5-32.6%, respectively, in patients. The parapharyngeal fat pad also correlates strongly with AHI.Conclusions: The findings in this study reveal that the amount of body weight and distribution of deposited fat both affect airway length, and therefore OSA. Fat distribution plays a larger impact than the amount of weight, and is a better predictor of who among obese people are more prone to OSA. [ABSTRACT FROM AUTHOR]

Background: Plants are always exposed to dynamic light. The photosynthetic light use efficiency of leaves is lower in dynamic light than in uniform irradiance. Research on the influence of environmental factors on dynamic photosynthesis is very limited. Nitrogen is critical for plants, especially for photosynthesis. Low nitrogen (LN) decreases ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and thus limits photosynthesis. The decrease in Rubisco also delays photosynthetic induction in LN leaves; therefore, we hypothesized that the difference of photosynthetic CO2 fixation between uniform and dynamic light will be greater in LN leaves compared to leaves with sufficient nitrogen supply. Results: To test this hypothesis, soybean plants were grown under low or high nitrogen (HN), and the photosynthetic gas exchange, enzyme activity and protein amount in leaves were measured under uniform and dynamic light. Unexpectedly, dynamic light caused less photosynthetic suppression, rather than more, in LN leaves than in HN leaves. The underlying mechanism was also clarified. Short low-light (LL) intervals did not affect Rubisco activity but clearly deactivated fructose-1,6-bisphosphatase (FBPase) and sedoheptulose-1,7-bisphosphatase (SBPase), indicating that photosynthetic induction after a LL interval depends on the reactivation of FBPase and SBPase rather than Rubisco. In LN leaves, the amount of Rubisco decreased more than FBPase and SBPase, so FBPase and SBPase were present in relative excess. A lower fraction of FBPase and SBPase needs to be activated in LN leaves for photosynthesis recovery during the high-light phase of dynamic light. Therefore, photosynthetic recovery is faster in LN leaves than in HN leaves, which relieves the photosynthetic suppression caused by dynamic light in LN leaves. Conclusions: Contrary to our expectations, dynamic light caused less photosynthetic suppression, rather than more, in LN leaves than in HN leaves of soybean. This is the first report of a stress condition alleviating the photosynthetic suppression caused by dynamic light. [ABSTRACT FROM AUTHOR]

Background: Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. Methods: We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3' untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients' response to gemcitabine. Results: A549-GR-derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients. Conclusion: Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: To provide evidence that the Chinese herbal medicine (CHM) PSORI-CM01 combined with Western medicine reduces the relapse rate of psoriasis vulgaris (PV), we plan to conduct a large-scale randomized control trial (RCT). In order to improve and perfect the RCT, this pilot study was designed to determine the feasibility and the potential of a modified protocol for the full-scale RCT.Methods: Eligible patients with psoriasis vulgaris (PV) were enrolled into a randomized comparison in which all subjects received topical sequential therapy and PSORI-CM01 or placebo for 12 weeks. The primary outcome measure was the relapse rate. Treatment response was computed from Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Dermatology Life Quality Index (DLQI). The secondary outcome measures included time to relapse, time to onset, rebound rate, PASI score, pruritus scores on the Visual Analog Scale (VAS), BSA, DLQI and SF-36 (short form health survey), and incidence of serious adverse events (SAEs).Results: Six of 7 (86 %) subjects reached the PASI-50 in the CHM group compared with nine of 10 (90 %) in the placebo group during the treatment period. Among the subjects who reached PASI-50, one out of six subjects (17 %) relapsed in the CHM group during the treatment period compared with six out of nine patients in the placebo group (67 %). No subjects met the rebound criteria. Changes to baseline in the PASI scores were not significantly different between the two groups (t = 1.764, P = 0.098).Conclusion: Oral PSORI-CM01 combined with topical sequential treatment showed a smaller recurrence rate (P = 0.118) than placebo combined with the same topical therapy for moderate-to-severe PV in this pilot study.Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/searchproj.aspx ) ChiCTR-TRC-13003233 ; date of registration: 15 April 2013. [ABSTRACT FROM AUTHOR]

Background: MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor β1(TGF-β1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-β1-involvement in the tumorigenesis of cervical cancer remain unknown. Methods: The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-β1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene. Results: miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-β facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-β1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-β1 partly through miR-106b and was involved in TGF-β1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay. Conclusion: Our data suggest that the TGF-β1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Background: An established body of literature has shown evidence of implicit bias in the health care system on the basis of patient race and ethnicity that contributes to well documented disparities in outcomes. However, little is known about the influence of patient race and ethnicity on the decision to order diagnostic radiology exams in the acute care setting. This study examines the role of patient race and ethnicity on the likelihood of diagnostic imaging exams being ordered during United States emergency department encounters.Methods: Publicly available data from the National Hospital Ambulatory Medical Care Survey Emergency Department sample for the years 2006-2016 was compiled. The proportion of patient encounters where diagnostic imaging was ordered was tabulated by race/ethnicity, sub-divided by imaging modality. A multivariable logistic regression model was used to evaluate the influence of patient race/ethnicity on the ordering of diagnostic imaging controlling for other patient and hospital characteristics. Survey weighting variables were used to formulate national-level estimates.Results: Using the weighted data, an average of 131,558,553 patient encounters were included each year for the 11-year study period. Imaging was used at 46% of all visits although this varied significantly by patient race and ethnicity with white patients receiving medical imaging at 49% of visits and non-white patients at 41% of visits (p < 0.001). This effect persisted in the controlled regression model and across all imaging modalities with the exception of ultrasound. Other factors with a significant influence on imaging use included patient age, gender, insurance status, number of co-morbidities, hospital setting (urban vs non-urban) and hospital region. There was no evidence to suggest that the disparate use of imaging by patient race and ethnicity changed over the 11-year study time period.Conclusion: The likelihood that a diagnostic imaging exam will be ordered during United States emergency department encounters differs significantly by patient race and ethnicity even when controlling for other patient and hospital characteristics. Further work must be done to understand and mitigate what may represent systematic bias and ensure equitable use of health care resources. [ABSTRACT FROM AUTHOR]

Background: Carcinoma-associated fibroblasts (CAFs) are dominant components of tumor microenvironment, which has been reported to promote development, progression, and metastasis of cancer. However, the role of CAFs during adhesion process remains unknown. It has been hypothesized that CAFs contribute to adhesion to endothelial cells of colorectal cancer (CRC) via HGF/c-Met pathway. Methods: Clinical specimen and orthotopic liver metastasis model was used to investigate association between CD44 expression and propensity of metastasis in CRC. Human CRC derived cancer associated fibroblasts was isolated and its effect on migration and adhesion of CRC cells was investigated. We also confirm the conclusion on animal metastasis model. Results: In this study, clinical specimen and orthotopic liver metastatic model indicated that overexpression of CD44 is associated with CRC metastasis, and we found that colorectal cancer-derived CAFs (CC-CAFs) increased the adhesion and migration of CRC cells in vitro through up-regulation of CD44, we also found that CC-CAFs promoted adhesion and liver or lung metastasis in vivo. Mechanistically, we found that the expression of HGF increased tenfolds compared CC-CAFs with adjacent normal fibroblasts, and HGF promoted adhesion through up-regulation of CD44 via HGF/c-MET signal pathway. Conclusions: These results indicated that CC-CAFs-derived HGF induced up-regulation of CD44 which mediated adhesion of CRC cells to endothelial cells, and subsequently resulted in enhancement of metastasis of CRC cells, it could provide a novel therapeutic or preventive target. [ABSTRACT FROM AUTHOR]

Background: Psoriasis causes worldwide concern because of its high-prevalence, as well as its harmful, and incurable characteristics. Topical therapy is a conventional treatment for psoriasis vulgaris. Chinese medicine (CM) has been commonly used in an integrative way for psoriasis patients for many years. Some CM therapies have shown therapeutic effects for psoriasis vulgaris (PV), including relieving symptoms and improving quality of life, and may reduce the relapse rate. However, explicit evidence has not yet been obtained. The purpose of the present trial is to examine the efficacy and safety of the YXBCM01 granule, a compound Chinese herbal medicine, with a combination of topical therapy for PV patients.Methods/design: Using an add-on design, the trial is to evaluate whether the YXBCM01 granule combined topical therapy is more effective than topical therapy alone for the treatment of PV. The study design is a double-blind, parallel, randomized controlled trial comparing the YXBCM01 granule (5.5 g twice daily) to a placebo. The duration of treatment is 12 weeks. A total of 600 participants will be randomly allocated into two groups, YXBCM01 granule group and placebo group, from 11 general or dermatological hospitals in China. Topical use of calcipotriol betamethasone for the first 4 weeks and calcipotriol ointment for the remaining 8 weeks will be the same standard therapy for the two groups. Patients will be enrolled if they have a clinical diagnosis of PV, a psoriasis area severe index (PASI) of more than 10 or body surface area (BSA) of more than 10%, but PASI of less than 30 and BSA of less than 30%, are aged between 18 and 65-years-old, and provide signed informed consent. The primary outcome, relapse rate, is based on PASI assessed blindly during the treatment. Secondary outcomes include: (i) relapse time interval, (ii) time to onset, (iii) rebound rate, (iv) PASI score, (v) cumulative consumption of medicine, (vi) the dermatology quality life index (DLQI), and (vii) the medical outcomes study (MOS) item short form health survey (SF-36). Analysis will be on intention-to-treat and per-protocol subject analysis principles.Discussion: To address the effectual remission of the YXBCM01 granule for PV, this trial may provide a novel regimen for PV patients if the granule can decrease relapse rate without more adverse effects.Trial Registration: Chinese Clinical Trial Registry (http://cwww.chictr.org): ChiCTR-TRC-13003233, registered 26 May 2013. [ABSTRACT FROM AUTHOR]