Search

Introduction: Chronic spontaneous urticaria (CSU) is a troublesome dermatological problem that can have a significant impact on quality of life. Previous studies have indicated that acupuncture may be beneficial for patients with CSU. However, well-designed studies determine the effects of acupuncture on CSU are rare. The aim of this study is to investigate the efficacy and safety of acupuncture treatment for patients with CSU., Methods and Analysis: This study is designed as a multicentre, parallel, three-arm, randomised, sham-controlled trial. A total of 330 patients diagnosed as CSU will be randomly allocated into three groups: the verum acupuncture group, the sham acupuncture group and the waiting-list control group in a 1:1:1 ratio. Patients in the verum and sham acupuncture groups will receive 16 treatment sessions over 4 weeks, while patients in the waiting-list control group will not receive any acupuncture treatment. The primary outcome is the changes of weekly urticaria activity scores at the end of treatment. Secondary outcomes include itching severity measurement, Dermatology Life Quality Index, Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index and serum total IgE level. Adverse events will be recorded during the study observation period. All patients who are randomised in this study will be included in the intention-to-treat analysis., Ethics and Dissemination: Ethical approval of this study has been granted by the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (TCM) (ID: 2019 kl-006), the Medical Ethic Committee of the First Hospital of Wuhan (ID: (2019) number 7)) and the Medical Ethics Committee of the First Hospital of Hunan University of TCM (ID: HN-LLKY-2019-017-01/03) in three clinical centres in China, respectively. The results will be disseminated through peer-reviewed journals., Trial Registration Number: ChiCTR1900022994., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although great potential hazards and threats still occur from sulfur mustard, there are no specific medicine or therapy for the intoxication of sulfur mustard. Herein, we have demonstrated a supramolecular approach for the detoxification of the sulfur mustard simulant CEES ( 4 ) in vitro and in vivo by carboxylatopillar[5]arene potassium salts (CP[5]AK 1 ) efficiently based on host-guest interactions. The encapsulation of CEES ( 4 ) by the cavity of the pillar[5]arene 2 is driven by C-H···π interactions between CEES ( 4 ) and the electron-rich cavity of pillar[5]arene 2 , which was investigated by 1 H NMR titration, density functional theory studies, and the independent gradient model studies. CEES ( 4 ) is degradated to the reactive sulfonium salts quickly in aqueous media, resulting in the alkylation of DNA and proteins. The sulfonium salts can be encapsulated by CP[5]AK 1 efficiently, which accelerates the degradation of the sulfonium salts about 14 times. The cell and animal experiments indicated that the bioactivities of the sulfonium salts are inhibited with the formation of stable host-guest complexes, and CP[5]AK 1 has a good therapeutic effect on the damages caused by CEES ( 4 ) at either pre- or post-treatments. Due to the low cytotoxicity and good therapeutic effect, the anionic pillar[5]arenes are expected to be developed as specific antidotes against sulfur mustard (HD).

Exosomes play a vital role in cell-cell communication within the cancer microenvironment. Exosomal long noncoding RNAs (lncRNAs) are important regulators in cancer development and are involved in multiple processes, including cancer cell proliferation, angiogenesis, metastasis, drug resistance, and immunomodulation. Changes in the levels of exosomal lncRNAs often appear with the occurrence and development of cancer. Therefore, exosomal lncRNAs can be used as biomarkers for cancer diagnosis and prognosis. Exosomal lncRNAs can also indicate the treatment response of patients receiving chemotherapy. Moreover, exosomal lncRNAs are potential therapeutic targets for cancer treatment. In this review, we summarize the role of exosomal lncRNAs in cancer biology as well as in clinical management. A more comprehensive and in-depth understanding of the role of exosomal lncRNAs in cancer may help us better understand the mechanism of cancer development and clinically manage cancer patients., (© 2021. The Author(s).)

Social interaction is of vital importance for human beings. While the hyperscanning approach has been extensively used to study interpersonal neural synchronization (INS) during social interactions, functional near-infrared spectroscopy (fNIRS) is one of the most popular techniques for hyperscanning naturalistic social interactions because of its relatively high spatial resolution, sound anatomical localization, and exceptionally high tolerance of motion artifacts. Previous fNIRS-based hyperscanning studies usually calculate a time-lagged INS using wavelet transform coherence (WTC) to describe the direction and temporal pattern of information flow between individuals. However, the results of this method might be confounded by the autocorrelation effect of the fNIRS signal of each individual. For addressing this issue, a method termed partial wavelet transform coherence (pWTC) was introduced, which aimed to remove the autocorrelation effect and maintain the high temporal-spectrum resolution of the fNIRS signal. In this study, a simulation experiment was performed first to show the effectiveness of the pWTC in removing the impact of autocorrelation on INS. Then, step-by-step guidance was offered on the operation of the pWTC based on the fNIRS dataset from a social interaction experiment. Additionally, a comparison between the pWTC method and the traditional WTC method and that between the pWTC method and the Granger causality (GC) method was drawn. The results showed that pWTC could be used to determine the INS difference between different experimental conditions and INS's directional and temporal pattern between individuals during naturalistic social interactions. Moreover, it provides better temporal and frequency resolution than the traditional WTC and better flexibility than the GC method. Thus, pWTC is a strong candidate for inferring the direction and temporal pattern of information flow between individuals during naturalistic social interactions.

Background: Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders, with the most significant negative impact on health-related quality of life. Despite that multiple systematic reviews and clinical trials have suggested that acupuncture could be effective for FC treatment, the comparative effectiveness among various acupuncture approaches has remained unknown. This protocol proposed a plan to assess and rank the effectiveness and safety of different acupuncture methods for patients with FC., Methods: We will search 8 bibliographic databases from their inception to 30 June 2021, including the Cochrane Central Register of Controlled Trials, MEDLINE (via PubMed), EMBASE, Allied and Complementary Medicine Database, the Chinese Biomedical Literature Database (CBM), Wanfang Database, VIP Database, and China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCT) examining acupuncture methods for FC will be considered. The primary outcome is a measurement of the weekly stool frequency [including bowel movement (BM), spontaneous bowel movement (SBM), and complete SBM]. There will be at least 2 reviewers in charge of study selection, data extraction, risk of bias assessment. Bayesian network meta-analysis will be conducted using ADDIS (Aggregate Data Drug Information System) V.1.16.8. Meta-regression and subgroup analyses will also be performed, if feasible, to address the potential causes of inconsistency and heterogeneity. Furthermore, the strength of evidence will be appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system., Discussion: In this study, we will provide evidence-based hierarchies for the effectiveness and safety of acupuncture therapies to manage constipated patients, assisting healthcare providers, physicians, and patients in making more informed treatment decisions., Trial Registration: This study has been registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) with a registration number CRD42021227920.

Interpersonal touch plays a key role in creating and maintaining affiliative pair bonds in romantic love. However, the neurocognitive mechanism of interpersonal touch in affiliative pair bonding remains unclear. Here, we hypothesized that interpersonal neural synchronization (INS) during interpersonal touch underlies affiliative pair bonding between romantic couples. To test this hypothesis, INS between heterosexual romantic couples and between opposite-sex friends was measured using functional near-infrared spectroscopy-based hyperscanning, while the pairs of participants touched or vocally communicated with each other. The results showed significantly greater INS between the mentalizing and sensorimotor neural systems of two members of a pair during interpersonal touch than during vocal communication between romantic couples but not between friends. Moreover, touch-induced INS was significantly correlated with the self-reported strength of romantic love. Finally, the results also showed that men's empathy positively modulated the association between touch-induced INS increase and the strength of romantic love. These findings support the idea that INS during interpersonal touch underlies affiliative pair bonding between romantic couples and suggest that empathy plays a modulatory role in the neurocognitive mechanism of interpersonal touch in affiliative pair bonding., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Compelling evidence suggests that phosphoprotein phosphatases (PPPs) are involved in a large spectrum of physiological and pathological processes, but little is known about their roles in pancreatic cancer. We investigated the expression level, prognostic value, and potential function of PPPs with data from Oncomine, GEPIA, THPA, and TCGA databases and an independent cohort of patients with pancreatic cancer. Among all the PPP catalytic subunits (PPPcs), the transcription levels of PPP1CA, PPP1CB, PPP3CA, PPP3CB, and PPP4C were higher in pancreatic cancer than in normal pancreas (P<0.01, fold change > 2). Kaplan-Meier analysis showed that high transcription levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, and PPP4C correlated with poorer survival. In contrast, patients with high levels of PPP3CB, PPP3CC, PPP5C, PPP6C, and PPEF2 had much better prognoses. Data from THPA and patients with pancreatic cancer enrolled in our hospital also confirmed the prognostic value of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, and PPP6C at the protein level. In addition, the Pearson Chi-square test showed that PPP3CB level was significantly correlated with T and N stages. GO and KEGG analyses showed that the genes and pathways related to the pathogenesis and progression of pancreatic cancer were greatly affected by alterations in PPPcs. Results of the present study suggest that PPP1CA, PPP1CB, PPP2CA, PPP2CB, and PPP3CA have deleterious effects but PPP3CB, PPP5C, and PPP6C have beneficial effects on pancreatic cancer., (© 2021 The Author(s).)

Background: There is limited consensus on whether metastatic patterns are correlated with prognosis and treatment efficacy in pancreatic cancer. A better understanding of clinical implication of the metastatic patterns is pivotal for therapeutic decision-making and drug development. Methods: This study included 977 patients with metastatic pancreatic cancer (MPC) in three cohorts. The training cohort included 273 patients from clinical trial NCT00574275 and 367 patients from clinical trial NCT01124786. As the validation cohort, 337 patients from Changzhou No.2 People's Hospital and Shanghai General Hospital were enrolled. The correlations between different patterns of metastases and clinicopathological characteristics were investigated with the Pearson Chi-Square test. Kaplan-Meier analysis and log-rank test were applied to analyze the survival outcomes among groups with different metastatic patterns. The prognostic value of the number of metastatic sites and other variables was evaluated using the Cox regression model. Results: MPC patients aged ≥65 years had a higher rate of lung metastasis and those with liver metastasis were prone to have a high level of carbohydrate antigen 19-9 (CA19-9). Additionally, patients with isolated lung metastasis had much better overall survival (OS) than those with isolated liver or peritoneum metastasis. Cox regression analyses showed that the number of metastatic sites was an independent prognostic factor for OS in patients with MPC. Furthermore, for patients with one-site or two-site metastasis, there was a significant difference in OS among patients receiving no chemotherapy, monotherapy and combination therapy. However, for patients with more than two metastatic sites, receiving combination therapy or monotherapy showed limited superiority in OS over receiving no chemotherapy. Conclusion: MPC patients with isolated lung metastasis had better OS than those with isolated liver or peritoneum metastasis. Moreover, the number of metastatic sites showed prognostic and predictive value in patients with MPC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Stable angina pectoris has a high prevalence and causes serious harm. Revascularization therapy can relieve angina pectoris to some extent, but it is not widely accepted in China due to the cost and secondary events. The Chinese proprietary medicine Danlou tablet has been widely used to treat angina pectoris, but previous trials had inadequate methodologies. In this study, we aim to conduct a randomized controlled trial to evaluate its efficacy and safety on stable angina., Methods and Analysis: This study is a WeChat-based randomized, double-blind, and placebo-controlled clinical trial in China. Eligible participants are adults (aged 30-75 years) with CT-confirmed stable angina and traditional Chinese medicine-diagnosed intermingled phlegm and blood stasis syndrome. A total of 76 participants will be randomly allocated in a 1:1 ratio to the oral Danlou tablet group (1.5 mg a time, 3 times daily for 28 days) or the placebo group. Patients are permitted concomitant use of routine medications during these 28 days. The primary outcome is angina frequency per week. The secondary outcomes include angina severity, angina duration, traditional Chinese medicine efficacy, the withdrawal rate of emergency medications, blood lipids, and electrocardiograph efficacy. The WeChat app will be used to remind patients to take their medicines and fill out the forms. All data will be recorded in case report forms and analyzed by Statistical Analysis System software., Ethics and Dissemination: This study has been approved by the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-225-KY)., Trial Registration Number: ClinicalTrials.gov, ID: ChiCTR1900028068.

Background: Previous studies have given an inaccurate assessment of the role of acupuncture in in vitro fertilization (IVF). We will use acupuncture doses as an entry point, discussing the dose-related effects of acupuncture therapy in women undergoing IVF., Methods: This study will search the following database: EMBASE, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and 4 Chinese databases. All databases will be searched from the date of database establishment to January 31, 2019. In addition, we will search possible studies which were included in previous meta-analyses. The primary outcomes are the clinical pregnancy rate (CPR) and the live birth rate (LBR). The secondary outcomes involved the biochemical pregnancy rate (BPR), the ongoing pregnancy rate (OPR), serum hormone level, the incidence of ovarian hyper-stimulation syndrome (OHSS), the cycle cancellation rates, and adverse events (AEs). After checking and integrating the raw data, we will use a 2-step to conduct the meta-analysis. Firstly, we will assess the effect of acupuncture on in vitro fertilization and embryo transfer (IVF-ET). Secondly, the meta-analysis will be performed for studies with similar total number of treatment sessions to investigate the dose-related effects of acupuncture. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted., Results: This study will investigate the relationship between pregnancy outcomes and the doses of acupuncture therapy in women undergoing IVF, and answer whether a higher-doses of acupuncture treatment will contribute to a better outcome of IVF-ET., Conclusion: The funding of this meta-analysis may provide convincing evidence for clinicians, benefitting more patients who crave children., Inplasy Registration Number: INPLASY202070072.

Introduction: Chronic pruritus (CP) frequently occurs in many skin and systemic diseases, and adversely affects quality of life. This systematic review aims to evaluate treatment effects of acupuncture on CP., Methods and Analysis: An electronic and manual search will be conducted for all acupuncture treatments for CP, from the inception date of predefined database up to 28 February 2020. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database and the Wanfang Database. Other sources, including existing systematic reviews, conference proceedings and reference lists of identified publications will also be searched. Additionally, any clinical randomised controlled trials related to acupuncture treatment for CP, regardless of the publication status and language limitations, will be included. Study selection, data extraction and research quality assessments will be conducted independently by two researchers. The primary outcome measures include the Visual Analogue Scale, Urdu 5D-Itch Scale or other validated scales implemented after at least 2 weeks of treatment. Secondary outcomes include the effective rate, Quality of Life Scale (eg, the EQ-5D third level, the Dermatology Life Quality Index, etc.), Pittsburgh Sleep Quality Index, recurrence rate during the follow-up period and adverse events. If possible, meta-analyses will be performed using RevMan V.5.3 statistical software; otherwise, a descriptive analysis or subgroup analysis will be conducted. The results will be presented as the risk ratio of the binary data and the mean difference (MD) or standardised MD of the continuous data., Ethics and Dissemination: This systematic review protocol does not require formal ethical approval because the data are not personalised. It will be published in peer-reviewed journals and presented at international academic conferences., Prospero Registration Number: CRD42019136727., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: There is a growing number of randomised controlled trials (RCTs) that focus on functional changes in the brain detected by functional MRI (fMRI) and gut microbiota composition changes after using probiotics.However, the effect of probiotics on functional changes in the brain through gut microbiota remains controversial in existing RCTs. Furthermore, to our knowledge, there is no systematic review to evaluate the effect of probiotics on functional changes in the brain through gut microbiota. Therefore, we aim to summarise literatures evaluating the potential association between probiotics, gut microbiota and functional changes in the brain to elucidate whether probiotics influence gut microbiota and affect functional changes in the brain through gut microbiota., Methods and Analysis: China National Knowledge Infrastructure, Wanfang Data, VIP Databases (the Chongqing VIP Chinese Science and Technology Periodical Database), SinoMed, PubMed, Web of Science, MEDLINE (The National Library of Medicine), EMBASE (Excerpt Medica Database), Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov will be searched until July 2019. The Grey Literature in Europe (OpenSIGLE) database and Google search engine will also be used. The reference lists of each included study will be reviewed to determine whether there are any further relevant studies. RCTs using probiotics compared with a placebo/control will be included. We will use risk of bias assessment and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. The results of the systematic review will be synthesised narratively in the domains of the three primary outcome measures: (1) Increased/decreased activity in brain regions or altered functional connectivity (FC) of brain detected by fMRI and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (2) Changes in composition and diversity of the gut microbiota and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (3) Increased/decreased activity in brain regions or altered FC of brain detected by fMRI and the changes in composition or diversity of the gut microbiota after administration of probiotics., Ethics and Dissemination: The results will be disseminated through a peer-reviewed publication. As no private and confidential patient data will be included in the reporting, there are no ethical considerations associated with this protocol., Prospero Registration Number: CRD42019145114., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To investigate the efficacy and safety of acupoint injection of Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN) in the treatment of chronic urticaria (CU)., Methods: The following databases will be searched from their inception: Medline, Embase, Pubmed, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure Database, China Biomedical Literature Database, China Science Journal Database, and Wanfang Database. All databases will be searched from the date of creation until October 2019. In addition, we will manually search the list of medical journals as a supplement. The scope of the search included randomized controlled clinical studies related to acupoint injection of BCG-PSN for CU. The primary outcome is the disease activity control. Secondary outcomes include response rate, adverse events, and recurrence rates. The Cochrane RevMan V5.3 Deviation Assessment Tool will be used to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The average difference, standard mean difference and binary data will be used to represent continuous results., Results: This study will comprehensively review the existing evidence on the treatment of CU by acupoint injection of BCG-PSN., Conclusion: This systematic review will provide a judgment basis for the effectiveness and safety of acupoint injection of BCG-PSN in the treatment of CU., Systematic Review Registration: PROSPERO, CRD42019139885.

Although lncRNAs lack the potential to be translated into proteins directly, their complicated and diversiform functions make them as a window into decoding the mechanisms of human physiological activities. Accumulating experiment studies have identified associations between lncRNA dysfunction and many important complex diseases. However, known experimentally confirmed lncRNA functions are still very limited. It is urgent to build effective computational models for rapid predicting of unknown lncRNA functions on a large scale. To this end, valid similarity measure between known and unknown lncRNAs plays a vital role. In this paper, an original model was developed to calculate functional similarities between lncRNAs by integrating heterogeneous network data. In this model, a novel integrated network was constructed based on the data of four single lncRNA functional similarity networks (miRNA-based similarity network, disease-based similarity network, GTEx expression-based network and NONCODE expression-based network). Using the lncRNA pairs that share the target mRNAs as the benchmark, the results show that this integrated network is more effective than any single networks with an AUC of 0.736 in the cross validation, while the AUC of four single networks were 0.703, 0.733, 0.611, and 0.602. To implement our model, a web server named IHNLncSim was constructed for inferring lncRNA functional similarity based on integrating heterogeneous network data. Moreover, the modules of network visualization and disease-based lncRNA function enrichment analysis were added into IHNLncSim. It is anticipated that IHNLncSim could be an effective bioinformatics tool for the researches of lncRNA regulation function studies. IHNLncSim is freely available at http://www.lirmed.com/ihnlncsim., (Copyright © 2020 Li, Zhao, Zhou, Zhou and Lang.)

High pressure processing (HPP) and treatment with the essential oil extract carvacrol had synergistic inactivation effects on Salmonella and Listeria monocytogenes in fresh ground chicken meat. Seven days after HPP treatment at 350 MPa for 10 min, Salmonella treated with 0.75% carvacrol was reduced to below the detection limit (1 log CFU/g) at 4°C and was reduced by ca. 6 log CFU at 10°C. L. monocytogenes was more sensitive to these imposed stressors, remaining below the detection limit during storage at both 4 and 10°C after HPP treatment at 350 MPa for 10 min following treatment with 0.45% carvacrol. However, pressure-injured bacterial cells may recover and lead to an overestimation of process lethality when a selective medium is used without proper justification. For HPP-stressed Salmonella, a 1- to 2-log difference was found between viable counts on xylose lysine Tergitol 4 agar and aerobic plate counts, but no significant difference was found for HPP-stressed L. monocytogenes between polymyxin-acriflavine-lithium chloride-ceftazidime-esculin-mannitol (PALCAM) agar and aerobic plate counts. HPP-induced bacterial injury and its recovery have been investigated by comparing selective and nonselective agar plate counts; however, few investigations have addressed this issue in the presence of essential oil extracts, taking into account the effect of high pressure and natural antimicrobial compounds (e.g., carvacrol) on bacterial survival in various growth media. Use of selective media may overestimate the efficacy of bacterial inactivation in food processing evaluation and validation studies, and the effects of various media should be systematically investigated.

Renal tubular epithelial cells (RTECs) play pivotal roles in the innate immune response in kidneys. Dendritic cell specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) functions as both the innate immune recognition receptor and the adhesion molecule. In our previous study, we found that DC-SIGN expression was induced in RTECs during renal inflammation. However, the underlying mechanism remains unclear. Here, we used the human renal proximal tubular epithelial cell lines (HK-2) to investigate the mechanism of TNF-α-induced expression of DC-SIGN. Our results showed that TNF-α up-regulated the expressions of DC-SIGN and Runt-related transcription factor 1 (RUNX1) in a time-dependent manner and that it up-regulated DC-SIGN promoter-driven luciferase activity in a dose-dependent manner. The mTOR inhibitor rapamycin and mTOR siRNA blocked the TNF-α-induced up-regulation of DC-SIGN expression. Meanwhile, DC-SIGN expression was also inhibited by RUNX1 siRNA and its inhibitor Ro5-3335. In addition, both mTOR and RUNX1 inhibitors attenuated TNF-α-induced the increase in DC-SIGN promoter-driven luciferase activity. Finally, we found that HK-2 cells exposed to rapamycin or mTOR siRNA reduced the TNF-α-induced up-regulation of RUNX1. In conclusion, these results indicated that the mTOR-RUNX1 pathway participates in the regulation of TNF-α-induced DC-SIGN expression in RTECs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Several treatments are beneficial for patients with cancer-related pain (CRP), and there are numbers of systematic reviews evaluating the effectiveness and safety of these treatments. However, the overall quality of the evidence has not been quantitatively assessed. The aim of this study is to overcome the inconclusive evidence about the interventions of CRP., Methods: We will perform an umbrella systematic review to identify eligible randomised controlled trials (RCTs). A comprehensive literature search will be conducted in MEDLINE, EMBASE, and the Cochrane library for systematic reviews, meta-analyses and RCTs. We will describe the general information of the RCTs for participants, interventions, outcome measurements, comparisons, and results. Network meta-analysis will be developed to determine the comparative effectiveness of the treatments., Results: The result of this network meta-analysis will provide direct and indirect evidence of treatments for CRP., Conclusion: The conclusion of our study will help clinicians and CRP patients to choose suitable treatment options., Ethics and Dissemination: Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences., Prospero Registration Number: CRD42019131721.

Joint biomechanical functions rely on the integrity of cartilage extracellular matrix. Understanding the molecular activities that govern cartilage matrix assembly is critical for developing effective cartilage regeneration strategies. This study elucidated the role of decorin, a small leucine-rich proteoglycan, in the structure and biomechanical functions of cartilage. In decorin-null cartilage, we discovered a substantial reduction of aggrecan content, the major proteoglycan of cartilage matrix, and mild changes in collagen fibril nanostructure. This loss of aggrecan resulted in significantly impaired biomechanical properties of cartilage, including decreased modulus, elevated hydraulic permeability, and reduced energy dissipation capabilities. At the cellular level, we found that decorin functions to increase the retention of aggrecan in the neo-matrix of chondrocytes, rather than to directly influence the biosynthesis of aggrecan. At the molecular level, we demonstrated that decorin significantly increases the adhesion between aggrecan and aggrecan molecules and between aggrecan molecules and collagen II fibrils. We hypothesize that decorin plays a crucial structural role in mediating the matrix integrity and biomechanical functions of cartilage by providing physical linkages to increase the adhesion and assembly of aggrecan molecules at the nanoscale.

Introduction: Salt intake is very high in China, with ≈80% being added by the consumers. It is difficult to reduce salt in such settings. Our previous study (School-based Education programme to reduce Salt(School-EduSalt)) demonstrated that educating schoolchildren, who then instructed their families to reduce the amount of salt used at home, is effective in lowering salt intake in both children and adults. Our team also developed an app called 'KnowSalt', which could help individuals to estimate their salt intake and the major sources of salt in the diet. Building on School-EduSalt and KnowSalt, we propose to develop a new app (AppSalt) focusing on salt reduction through education, target setting, monitoring, evaluation, decision support and management to achieve a progressive lower salt intake for long term. To evaluate the effectiveness of the AppSalt programme, we will carry out a cluster randomised controlled trial., Methods and Analysis: We will recruit 54 primary schools from urban and rural areas of three provinces in China. A total of 594 children aged 8-9 years and 1188 adult family members will be randomly selected for evaluation. After baseline assessment, schools will be randomly allocated to either the intervention or control group. Children in the intervention group will be taught, with support of AppSalt, about salt reduction and assigned homework to get the whole family involved in the activities to reduce salt consumption. The duration of the intervention is two school terms (ie, 1 year). The primary outcome is the difference between the intervention and control group in the change of salt intake as measured by 24-hour urinary sodium., Ethics and Dissemination: The study has been approved by Queen Mary Research Ethics Committee and Peking University Health Science Centre IRB. Results will be disseminated through presentations, publications and social media., Trial Registration Number: ChiCTR1800017553., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Naïve and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Flow cytometry was performed to evaluate the level of baseline peripheral naïve and memory T cells from 137 APC patients before receiving first-line chemotherapy. Interrelationships between naïve, memory T cells and clinicopathological variables were evaluated using Pearson's correlation. The prognostic impact of naïve and memory T cells were assessed by Kaplan-Meier analysis and Cox regression. The correlation between naïve/memory T cells and tumor progression was investigated by Student's t test. CD4 + naïve/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8 + naïve/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4 + CD45RO + /CD4 + was correlated with better overall survival (OS) (P = 0.036). Patients with CD4 + naïve/memory ratio ≥0.36 had a poorer OS than those with CD4 + naïve/memory ratio <0.36 (P = 0.021). In addition, CD4 + naïve/memory ratio showed independent prognostic impact (HR 1.427, 95% CI 1.033-1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8 + naïve/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with a lower level of CD8 + naïve/memory ratio had longer progression-free survival (PFS) (P = 0.028). We propose CD4 + naïve/memory ratio as a novel prognostic biomarker for APC. In addition, CD8 + naïve/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We consider modeling non-autonomous dynamical systems for a group of subjects. The proposed model involves a common baseline gradient function and a multiplicative time-dependent subject-specific effect that accounts for phase and amplitude variations in the rate of change across subjects. The baseline gradient function is represented in a spline basis and the subject-specific effect is modeled as a polynomial in time with random coefficients. We establish appropriate identifiability conditions and propose an estimator based on the hierarchical likelihood. We prove consistency and asymptotic normality of the proposed estimator under a regime of moderate-to-dense observations per subject. Simulation studies and an application to the Berkeley Growth Data demonstrate the effectiveness of the proposed methodology.

Recently, a series of xanthone analogues has been identified as α-glucosidase inhibitors. To provide deeper insight into the three-dimensional (3D) structural requirements for the activities of these molecules, CoMFA and CoMSIA approaches were employed on 54 xanthones to construct 3D-QSAR models. Their bioactive conformations were first investigated by docking studies and optimized by subsequent molecular dynamics (MD) simulations using the homology modeled structure of the target protein. Based on the docking/MD-determined conformers, 3D-QSAR studies generated several significant models in terms of 47 molecules as the training set. The best model (CoMSIA-SHA) yielded q 2 of 0.713, r 2 of 0.967 and F of 140.250. The robustness of the model was further externally confirmed by a test set of the remaining molecules (q 2  = 0.793, r 2  = 0.902, and k = 0.905). Contour maps provided much information for future design and optimization of new compounds with high inhibitory activities towards α-glucosidase. Graphical Abstract CoMSIA/SHA contour map of xanthone α-glucosidase inhibitor.

Acupuncturists in all ages emphasize deqi ( qi arrival). We arranged and analyzed contents on deqi and qi arrival electronic texts in 1156 ancient medical books through Chinese Medical Code , the major electronic series of books on TCM, with medical classics as well as acupuncture-moxibustion and tuina parts as the emphasis. It is found that deqi is a standard for traditional acupuncture effect evaluation. Meanwhile, it acts on regulating body cold, heat, insufficiency and excess, guiding reinforce-reducing manipulation, determining needle depth, retaining and withdrawing, as well as prognosis, etc. Deqi takes the priority in clinical and scientific research.

Computational fluid dynamics was used to investigate the effect of the pathogenesis of membranous obstruction of inferior vena cava of Budd-Chiari syndrome with various angles between right hepatic vein and inferior vena cava.Mimics software was used to reconstruct the models from magnetic resonance imaging(MRI)angiograms of inferior vena cava,right hepatic vein,middle hepatic vein and left hepatic vein,and 3DMAX was used to construct the models of 30°,60°,90°and 120°angles between right hepatic vein and inferior vena cava,which was based on the reconstructed models.The model was conducted with clinical parameters in terms of wall shear stress distribution,static pressure distribution and blood velocity.The results demonstrated that the differences between wall shear stress and static pressure had statistical significance with various angles between right hepatic vein and inferior vena cava by SPSS.The pathogenesis of membranous obstruction of inferior vena cava had a correlation with the angles between right hepatic vein and inferior vena cava.

Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of -14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

Metabonomics methods have gradually become important auxiliary tools for screening disease biomarkers. However, recognition of metabolites or potential biomarkers closely related to either particular clinical symptoms or prognosis has been difficult. The current study aims to identify potential biomarkers of functional dyspepsia (FD) by a new strategy that combined hydrogen nuclear magnetic resonance ((1)H NMR)-based metabonomics techniques and an integrative multi-objective optimization (LPIMO) method. First, clinical symptoms of FD were evaluated using the Nepean Dyspepsia Index (NDI), and plasma metabolic profiles were measured by (1)H NMR. Correlations between the key metabolites and the NDI scores were calculated. Then, LPIMO was developed to identify a multi-biomarker panel by maximizing diagnostic ability and correlation with the NDI score. Finally, a KEGG database search elicited the metabolic pathways in which the potential biomarkers are involved. The results showed that glutamine, alanine, proline, HDL, β-glucose, α-glucose and LDL/VLDL levels were significantly altered in FD patients. Among them, phosphatidycholine (PtdCho) and leucine/isoleucine (Leu/Ile) were positively and negatively correlated with the NDI Symptom Index (NDSI) respectively. Our procedure not only significantly improved the credibility of the biomarkers, but also demonstrated the potential of further explorations and applications to diagnosis and treatment of complex disease.

Introduction: Functional constipation (FC) is a common gastrointestinal disease. Systematic reviews indicate that acupuncture may be effective for patients with FC. However, this conclusion is not convincing due to the quality, sample size and methodological heterogeneity of the studies included by these systematic reviews. Therefore, it is necessary for us to conduct a meta-analysis of individual patient data (IPD) from high-quality clinical trials to determine whether acupuncture is effective for patients with FC., Methods and Analysis: Randomised controlled trials (RCTs) of acupuncture for adult patients with FC will be searched in several databases from inception to April 2015. The corresponding authors of eligible studies will be contacted and invited to contribute raw data. The primary outcome is the change in spontaneous defaecation per week from baseline. The secondary outcomes include the proportion of responders, changes in stool quality, mean transit time, proportion of patients using laxatives and adverse events. We will check all of the data and perform reanalysis according to the statistical methodology reported in previous publications. Then we will harmonise the raw data and use a two-step method to conduct the IPD meta-analysis. First, we will calculate the effect size of acupuncture of each trial by analysis of covariance, with the principal end point as the dependent variable and the baseline scores as the covariates. Second, the effect size of acupuncture in each original study will be combined in the meta-analysis., Dissemination: On the basis of the IPD meta-analysis of high-quality RCTs, this review will answer the question of whether acupuncture is effective for FC. The findings of the review will be disseminated through peer-review publications and conference presentations., Trial Registration Number: PROSPERO 2014 CRD42014009901., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Salmonella contamination on raw shrimp is a big food safety concern in the United States currently. This research evaluated the inhibition effects of vapor phase thymol, modified atmosphere (MA), and their combination against Salmonella spp. on raw shrimp. Growth profiles of a Salmonella spp. cocktail (6 strains), inoculated onto the surface of raw shrimp, treated with vapor phase thymol at 3 levels (0, 0.8, and 1.6 mg/L), or MA (59.5% CO2 + 39.5% N2 + 1% O2 ), both alone and in combination, at 3 temperatures (8, 12, and 16 ºC), were determined. Lag time and maximum growth rate of Salmonella spp. under each treatment were obtained using Baranyi and Roberts models. Results indicated that both vapor phase thymol and MA treatments alone inhibited the growth potential of Salmonella spp. effectively, extending the lag time by 10% to 100% and reducing the maximum growth rate by 14% to 71% compared with controlled samples at experimental temperatures (8, 12, and 16 ºC). Combination treatments of vapor phase thymol and MA exhibited greater inhibition effectiveness than each individual treatment and a synergistic antimicrobial effectiveness could be observed on the lag time extension. To the maximum, at 12 ºC, lag time of Salmonella spp. was extended 59.6% more by the combination treatment of 0.8 mg/L thymol + MA (36.97 h) than those effects combined from 0.8 mg/L thymol treatment and MA treatment alone (23.16 h in total). This combination strategy could be potentially utilized for Salmonella inhibition during the long distance and temperature-abused raw shrimp import process., (© 2013 Institute of Food Technologists®)

The conventional chemotherapy agent, doxorubicin, is of limited clinical use because of its systemic toxicity toward normal healthy tissue. A new doxorubicin conjugate with α-linolenic acid showed good anti-tumor activity with lower toxicity than free doxorubicin and exhibited an active tumor-targeting profile due to the introduction of α-linolenic acid which might be an effective tumor-targeting moiety for the modification of chemotherapeutics.