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Yuting He,1,2,* Chen Xue,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Gallbladder cancer (GBC) is a highly lethal disease and the most common biliary tract malignant tumor with poor prognosis. Accumulating evidence indicates that cluster of differentiation 44 (CD44) is overexpressed in several malignancies and has a crucial role in the development of cancer. However, its expression and function in GBC are unclear. The aim of this study was to explore CD44 expression and its role in GBC. Materials and methods: The expression of CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to confirm the relationship between CD44 expression and clinical outcomes of GBC patients. EDU assay, colony formation assay, cell migration and invasion assay were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with si-RNA. Results: CD44 was overexpressed and associated with poor outcomes in GBC patients. The univariate and multivariate analyses confirmed that elevated CD44 was an independent prognostic factor for the OS of GBC patients. Silencing CD44 could suppress the GBC cell proliferation, migration and invasion in vitro, as well as attenuated cancer stem cell functions. Conclusion: CD44 markedly correlated with aggressive tumor behaviors and contributed to the progression of GBC, which could represent a novel prognostic marker and potential therapeutic target for GBC patients. Keywords: CD44, gallbladder cancer, cancer stem cells, tumor progression

It is important to characterize conditions under which atrial fibrillation (AF) is likely to terminate spontaneously. A novel method is proposed here. Eleven features are first extracted to characterize RR interval and Poincaré plot from a statistical viewpoint and a geometric viewpoint respectively. Then sequential forward search (SFS) algorithm is utilized for feature selection. Finally, a fuzzy support vector machine (FSVM) with a new fuzzy membership is applied for AF termination prediction. The method is studied with an AF database of electrocardiogram (ECG) recordings provided by PhysioNet for the Cardiology Challenge 2004. It is divided into a training set and two testing sets (A and B). Experiment results show that 100 per cent of testing set A and 100 per cent of testing set B are correctly classified, together with 92.3 per cent of non-terminating and soon-terminating AF correctly classified. It demonstrates that the proposed method can predict spontaneous termination of AF effectively. [ABSTRACT FROM AUTHOR]

In this study, we investigated the serum vitamin D level in overweight individuals and its correlation with the incidence of nonalcoholic fatty liver disease (NAFLD). Between May 2020 and May 2021, the Department of Gastroenterology at the People's Hospital of Henan University of Traditional Chinese Medicine treated a total of 321 outpatients and inpatients with NAFLD, who were included in the NAFLD group, while 245 healthy age- and gender-matched individuals were included in the control group. All the data were collected for the relevant indices, including fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine transaminase, and 25-hydroxy vitamin D (25[OH]D. The patients with NAFLD were divided into the normal BMI group, the overweight group, and the obese group, according to the body mass index, and the 25(OH)D levels were compared between the different groups. Spearman's correlation analysis was performed to analyze the correlation between the serum 25(OH)D level and NAFLD. Regarding the serum 25 (OH)D level, it was lower in the NAFLD group than in the control group ([18.36 + 1.41] µg/L vs [22.33 + 2.59] µg/L, t = ?5.15, P<0.001), and was lower in the overweight group than in the normal group ([18.09 ± 5.81] µg/L vs [20.60 ± 4.16] µg/L, t = 0.26, P = 0.041). The serum 25(OH)D level was thus negatively correlated with the incidence of NAFLD in overweight individuals (r = 0.625, P<0.05). In conclusion, the level of 25(OH)D decreased in patients with NAFLD with increasing BMI (normal, overweight, obese). Keywords: Nonalcoholic fatty liver disease, Vitamin D.

Objective: Studies have shown that Wuzi Yanzong Pill (WYP) can be used to treat neurological diseases, but its mechanisms for multiple sclerosis (MS) remain unclear. This study aims to determine the effect of WYP on MS in an animal model of experimental autoimmune encephalomyelitis (EAE), and explore its mechanism. To provide theoretical basis for the clinical treatment of MS with WYP., Methods: C57BL/6 female mice were randomly divided into Blank control, EAE control, low dose WYP, medium dose WYP, and high dose WYP groups. One week before model generation, the mice were gavaged with saline (50 mL/kg/d) in Blank control and EAE control groups. The treatment groups was gavaged with different doses of WYP solution (4, 8, or 16 g/kg/d respectively) Clinical scores were recorded daily. Sample collection was conducted on the 14th and 28th days, respectively The expressions of IL-10, IL-17, IL-12, TNF-α and IFN-γ in spleen were detected by ELISA. The expressions of ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, CCR2 in spleen, brain and spinal cord were detected by Western Blot. The types of macrophages and the contents of intracellular IL-10 and IL-12 were detected by Flow Cytometry. The contents of TNF-α and TLR4 mRNA in the spleen were detected by RT-PCR., Results: WYP treatment improved the clinical score of EAE mice in a significant dose-dependent manner, with the WYP high-dose group showed the most significant improvement in clinical score. Compared with the EAE control group, WYP high dose group had significantly lower levels of IL-17, IFN-γ, ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, and CCR2 as well as TNF-α and TLR4 mRNA, but increased the number of M 2 macrophages and IL-10., Conclusion: WYP treatment relieves clinical symptoms in EAE mice, which may be related to regulate inflammatory pathway and inhibiting expressions of inflammatory cytokines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Recently, 3D dental intraoral scanning technology has been developed rapidly and applied widely in everyday dental practice. Since 3D dental scanning could provide valuable personal information, it enabled researchers to develop novel procedures for individual identification through 3 D- 3 D dentition superimposition. This study aimed to test the applicability of this method in an Eastern Chinese population and propose a threshold for personal identification. For this purpose, 40 volunteers were recruited, and the initial 80 (upper and lower) 3D intraoral scans (IOS) were collected. After one year, 80 IOS of these volunteers were repeatedly collected. In addition, the other 120 IOS of 60 patients were extracted from the database. The 3D models were trimmed, aligned, and superimposed via Geomagic Control X software, and then the root mean square (RMS) value of point-to-point distance between the two models was calculated. The superimposition of two IOS belonging to the same individual was considered as a match, and superimposition of two IOS belonging to different individuals was considered as a mismatch. Totally, superimpositions of 80 matches and 3120 mismatches were obtained. Intra- and inter-observer errors were assessed through the calculation of relative technical error of measurement (rTEM). Mann-Whitney U test verified possible statistically significant differences between matches and mismatches (P < 0.05). The rTEM of intra- and inter-observer repeatability analyses was lower than 4.7 %. The range of RMS value was 0.05-0.18 mm in matches and 0.72-2.28 mm in mismatches without overlapping. The percentage of accurate identification reached 100 % in blind test through an arbitrary RMS threshold of 0.45 mm. The results indicated that individual identification through the 3 D- 3 D dentition superimposition was effective in Eastern Chinese population. Successful identification could be achieved with high probability when the RMS value of the point-to-point distance of two dentitions is <0.45 mm., Competing Interests: Declaration of Competing Interest The authors declare that they have no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice., Methods: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot., Results: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01)., Conclusions: WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Emotional disorders are often observed in inflammatory bowel disease (IBD). IBD with emotional disorders leads to poor quality of life. This systematic review aims to assess the effectiveness of acupuncture in patients with IBD with emotional disorders., Methods and Analysis: Nine electronic databases, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing & Allied Health Literature, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database, will be searched from inception to October 2021 without language restriction. The grey literature containing conference proceedings, as well as systematic reviews listed in the reference of definite publications, will also be retrieved. Randomised controlled trials either in English or Chinese reporting acupuncture therapy for IBD with emotional disorders will be included. The primary outcome is changes of emotional functioning outcomes. The Colitis Activity Index, Crohn's Disease Activity Index, C reactive protein and adverse events will be assessed as the secondary outcomes. More than two assessors will conduct the study retrieval and selection, as well as the data extraction and evaluation of the risk of bias. Data synthesis will be performed using a random-effects model based on the results of heterogeneity. Data analysis will be performed using RevMan software (V.5.4). Moreover, the dichotomous data will be presented as risk ratios, and the continuous data will be calculated using weighted mean difference or standard mean difference., Ethics and Dissemination: This systematic review contains no individual patient data; thus, ethical approval is not required. Moreover, this review will be disseminated in a peer-reviewed journal or relevant conference., Prospero Registration Number: CRD42020176340., 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.)

Background: The number of systematic reviews meta-analyses (SRs/MAs) on the effectiveness of acupuncture for angina pectoris (AP) is increasing. Due to the inconsistent conclusions and unknown quality of these SRs/MAs, this overview aimed to systematically evaluate and synthesize the existing SRs/MAs, attempting to provide more reliable evidence for the effectiveness and safety of acupuncture in the treatment of AP., Methods: SRs/MAs were searched via eight databases from inception to March 14, 2022. The risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool. The quality of the methodology, reporting, and evidence were assessed by the Assess Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Item for Systematic Review and Meta-analysis for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively., Results: Sixteen SRs/MAs were included and fifteen SRs/MAs were considered being of critically low quality according to AMSTAR-2. Only three SRs/MAs were rated at low risk of bias. No study reported all the items listed in the PRISMA-A checklist. No high-quality evidence with GRADE assessment was found. With the low-quality evidence, acupuncture combined with other interventions was superior to monotherapy (medications or Chinese medicine) in the angina symptom and electrocardiogram recovery. No adverse effects owing to acupuncture were reported., Conclusions: Owing to the lack of high-quality evidence provided by the current SRs/MAs, the effectiveness of acupuncture for AP still warrants further proof. Further researches with more critical design and methodology are needed for providing more convincing evidence., Registration: This review was registered at PROSPERO (www.crd.york.ac.uk/prospero/): CRD42021219367., (© 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Background: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear., Methods: This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes., Discussion: We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD., Trial Registration: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021., (© 2022. The Author(s).)

Background: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure., Objectives: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China., Methods: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations., Results: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group., Conclusions: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV., (© 2021 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Introduction: Acupuncture is an efficacious and safe treatment choice for migraine prevention. Results from clinical trials have shown that non-specific effects play an important role in acupuncture's efficacy. To date, however, there is no evidence available quantitatively evaluating the effect of non-specific effects, such as patients' expectations and beliefs for acupuncturists, on acupuncture efficacy, necessitating further exploration., Methods: A total of 156 patients with migraine without aura (MwoA) will be randomized to either junior or senior acupuncturist group, at a ratio of 1:1. The study will last 24 weeks, for each patient, comprising baseline, treatment, and follow-up phases lasting 4, 8, and 12 weeks, respectively. All patients will undergo 12 sections of acupuncture treatment delivered by either a junior or senior acupuncturist following the same acupuncture prescription and manipulation. The primary outcomes will be changes in the number of migraine days and frequency of attacks per 4 weeks cycle, relative to the baseline. Secondary outcomes will include severity of headache pain, quality of life, anxiety/depression levels, and use of non-steroidal anti-inflammatory drugs (NSAIDs) per 4 weeks cycle, compared to the baseline, as well as adverse events and rate of positive response to treatment. Prior to randomization of patients into junior or senior acupuncturist groups, the Acupuncture Expectations Evaluation Scale (AES) will be used to evaluate their expectations and belief with regards to acupuncture efficacy delivered by senior or junior acupuncturists., Discussion: Results from this clinical randomized controlled trial will help to quantitatively evaluate the extent of the effect of acupuncture treatment delivered by a senior or junior acupuncturist (high relative to low expectations) in migraine patients., Ethics and Dissemination: This trial has been approved by the Institutional Review Boards and Ethics Committees of Hospital of Chengdu University of Traditional Chinese Medicine (Approval No. 2020KL-058)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Jiang, Fang, Zhang, Cheng, Li, Hu, Sun, Zheng, Huang, Zeng, Liang and Li.)

Introduction: Previous reviews have suggested that the effectiveness of acupuncture for inflammatory bowel disease (IBD) has not well been demonstrated due to the limited randomised controlled trials (RCTs). In recent years, the growing research on acupuncture for IBD make it possible to conduct a further systematic review and synthesise more sufficient clinical data to evaluate the effectiveness and safety of acupuncture for IBD., Methods and Analysis: Nine electronic databases without language restriction will be retrieved from inception to March 2021, including the Cochrane Library, MEDLINE, EMBASE, Ovid, the Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing Chinese Science and Technology Periodical Database and Wanfang Database. The RCTs on acupuncture for IBD will be included. The data screening, data extraction and the assessment of risk bias will be performed respectively by two reviewers. The quality of evidence will be evaluated by using the Grading of recommendation Assessment, Development and Evaluation application. The meta-analysis will be performed if heterogeneity analysis conducted on the RevMan software (V.5.3) is insignificant. The primary outcome was symptoms alleviation after acupuncture treatment or even in the follow-up., Ethics and Dissemination: Ethical approval will not be needed because data of this review are not involved in patient's information and privacy. The results will be published and diffused in a peer-reviewed journal or relative conferences., Trial Registration Number: CRD42020157903., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is growing interest in identifying trainees with surgical aptitude predictive of eventual technical proficiency. Musical tasks involve complex, cerebral activity, and ambidextrousity, which may have a positive impact on the acquisition of surgical skill sets. The purpose of this study was to investigate the influence of prior musical experience on the performance of basic surgical skills., Methods: This was a prospective cross-sectional study involving 51 novice undergraduate and medical school trainees with no prior surgical exposure. Musicality was assessed with a detailed survey and objectively with the Mini-Profile of Music Perception Skills test. Dexterity was assessed using the Purdue Pegboard test. Surgical skills were then evaluated by performing 2 timed suturing trials after observing tutorial video, followed by a timed laparoscopic peg transfer test. Outcomes included both speed and quality of performance., Results: Participants with prior musical experience performed better than nonmusicians on the Mini-Profile of Music Perception Skills test (P = .015), dominant hand dexterity (P = .05), suture quality (P < .03), and laparoscopic peg transfer speed (P < .01). There was no significant difference in the suturing speed between musicians and nonmusicians. The dexterity and Mini-Profile of Music Perception Skills scores were predictive of suture quality (P < .01). Among musicians, duration of musical training, inactivity, instrument type, and certification levels did not correlate with differences in surgical task performance., Conclusion: Musical background is associated with better performance of fundamental surgical skills among surgical novices, particularly technique quality. Although this does not imply superior ultimate surgical ability, musicality may be a marker for basic surgical skill development useful in identifying suitable candidates for surgical training., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The network analysis method based on brain connectomics is an important entry point to explore the working mechanism of brain and is also the current trend of researches on acupuncture stimulation-induced changes of neuroimages. We, in the present review, summarized the common network analysis methods for exploring the underlying mechanisms of brain network-mediated regulatory effects of acupuncture interventions. Moreover, combining the current research development and our team's previous research findings, we extracted the characteristics of targeting, conditionity and dynamic of regulatory effects of acupuncture-activated brain network, and put forward our prospects about the future research from the aspects of new scanning modes (for instance, multimodal data acquisition of magnetic resonance, electroencephalogram, near infrared spectrum, etc.), network analysis (such as Granger causality analysis, complex network measures, whole-brain connectivity dynamics tracking, high-order resting-state functional connectivity analysis, etc.) and experimental research paradigms (for example, introduce of transcranial magnetic stimulation induced transient changes of brain functional activity, machine learning approach, etc.).

Background: As it has been recorded in ancient Chinese classics, Yanglingquan (GB34) and Dannangxue (EX-LE6) are two important acupoints that can regulate the function of the gallbladder. Acupuncture at these two acupoints is considered particularly effective for gallbladder disease treatment, especially for alleviating gallbladder stone disease (GSD) symptoms that can be aggravated after intaking high-fat food. However, the superior effect between the two acupoints still needs to be further explored, as well as the underlying central mechanism has never been investigated to date., Methods and Design: Ninety participants diagnosed with GSD will be randomly divided into group A (acupuncture at GB34), group B (acupuncture at EX-LE6), and group C (acupuncture at non-acupoint) in a ratio of 1:1:1. All of them will receive a 30-min acupuncture treatment with fatty-food cues being presented before and after acupuncture. During the task, participants will be scanned by MRI and required to rate their desire for high-/low-fat food with an 11-point Likert scale. Additionally, the participants' pain/discomfort sensation will be evaluated using the Numeric Rating Scale (NRS) at four timepoints, including before the 1st task fMRI scan, before and after acupuncture, and after the 2nd task fMRI scan. For both behavior and fMRI data, the ANOVA analysis will be conducted among three groups to testify the immediate effect of GB34 and EX-LE6. The post hoc t-test will be employed to further explore the superiority between acupuncture with GB34 and EX-LE6. Furthermore, correlation analyses will be conducted to investigate a possible correlation between neural changes and clinical data., Discussion: In comparison to the non-acupoint, the results will firstly explore the superior effect between acupuncture with GB34 and EX-LE6 on GSD patients by observing their behavioral and neural response change to fatty-food cue, and then to investigate the underlying central mechanism., Trial Registration: Chinese Clinical Trial Registry ChiCTR2000034368 . Registered on 3 July 2020.

The application progress of machine learning in research of acupuncture and moxibustion was reviewed from three aspects: mining of acupuncture and moxibustion prescription and indications, acupuncture efficacy prediction and its influencing factors, acupoint specificity and acupuncture manipulation research, and the existing problems in current research and future research trends were discussed. It is believed that the appropriate machine learning algorithm should be selected to build the model according to the research purpose and data characteristics in the future research; attention should be paid to feature design, feature selection and feature cleaning; sample data collection should be a priority, and data sharing platform and standardized data collection should be developed to improve the data quality.

Rhubarb-Aconite Decoction (RAD), a famous Chinese medicine prescription, has been widely used for treating intestinal injury. However, the effect of RAD on intestinal epithelial cells is unclear. The aim of this study was to investigate the effects of RAD drug-containing serum on the oxidative stress injury and inflammatory response induced by endotoxin (ET) in Caco-2 cells in vitro. Lipid peroxide malondialdehyde (MDA), lactate dehydrogenase (LDH), caspase-11, tumor necrosis factor- α (TNF- α ), interleukin-3(IL-3), and cytokeratin (CK)18, adenosine triphosphate (ATP) activity, and intracellular free calcium ion levels were measured. The results showed that ET triggered the activation of caspase-11 and the massive release of TNF- α , increased the inhibitory rate of cell growth, MDA, and LDH expressions in Caco-2 cells. Moreover, RAD drug-containing serum could inhibit caspase-11 activation, decrease the release of TNF- α and IL-3, reduce intracellular free calcium ion, and enhance CK 18 expression and ATP activity. These novel findings demonstrated that ET-induced oxidative stress injury and inflammatory response of Caco-2 cells were improved by RAD drug-containing serum, indicating that RAD may be a good choice for the treatment of intestinal injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Xiao-hong Du et al.)

Objective: To explore the clinical therapeutic effect of acupuncture combined with opioid drugs on moderate and severe cancer pain., Methods: A total of 60 patients with cancer were randomized into an observation group and a control group, 30 cases in each group. Oxycodonehydrochloride prolonged-release tablet was taken orally in the control group. On the basis of the control group, acupuncture was applied at Hegu (LI 4), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6), etc. Corresponding back- shu points, xi -cleft points and ashi points were selected additionally according to primary viscera and pain sites in the observation group. The treatment was given once a day for 2 weeks. Symptomatic and supportive treatment were implanted, and no other antalgic measures were given during the trial. The daily dosage of opioid drug and the adverse reactions were recorded in both groups. Karnofsky performance status (KPS) and quality of life (QOL) scale scores were compared before and after treatment. Numerical rating scale (NRS) score was calculated to evaluate the clinical therapeutic effect., Results: Compared before treatment, the daily dosage of opioid drugs after treatment was obviously reduced in the observation group ( P <0.01), and was obviously increased in the control group ( P <0.05). The dosage of opioid drugs after treatment in the observation group was much less than the control group ( P <0.01). After treatment, the KPS and QOL scores were increased in both groups ( P <0.01), and the scores in the observation group were superior to the control group ( P <0.01, P <0.05). The analgesic effective rate was 90.0% (27/30) in the observation group, which was superior to 76.7% (23/30) in the control group ( P <0.05). The adverse reactions rate in the observation group was lower than the control group ( P <0.01)., Conclusion: Acupuncture combined with opioid drugs can effectively relieve the cancer pain, improve the performance status and quality of life in cancer patients, reduce the dosage of opioid drugs and adverse reactions rate.

Introduction: Migraine is the second-leading cause of years lived with disability worldwide. The high prevalence of migraine-related emotional disorders is often overlooked. Acupuncture is often used to treat both migraine and emotional disorders. This systematic review protocol aims to analyse whether acupuncture is effective for treating emotional disorders in patients with migraine., Methods and Analysis: Nine databases will be searched from inception to may 2019: cochrane central register of controlled trials, medline, embase, allied and complementary medicine database, cinahl, china national knowledge infrastructure, chinese biomedical literature database, vip database and wanfang database. Randomised controlled trials (rcts) of acupuncture therapy for migraine with emotional functioning outcomes, which were reported in chinese or english, will be included. The primary outcome is the change in emotional functioning. Study selection, data extraction and assessment of the risk of bias will be performed independently by two or more reviewers. Revman software (v.5.3) will be used to perform the assessment of the risk of bias and data synthesis., Ethics and Dissemination: Ethics approval is not be needed because the data will not contain individual patient data, and there are no concerns about privacy. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal or relevant conference., Trial Registration Number: CRD42019139433., 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.)

Objective: The aim of this study was to explore the effect of micro-ribonucleic acid (miR)-146a on acute gouty arthritis rats through Toll-like receptor-4/myeloid differentiation factor 88 (TLR4/MyD88) signal transduction pathway., Materials and Methods: A total of 30 clean-grade Sprague-Dawley rats were divided into three groups, including agomiR-146a group (n=10), antagomiR-146a group (n=10) and negative control group (NC, n=10). The model was successfully established via a one-time injection of sodium urate into ankle joint cavity. Subsequently, agomiR-146a (10 μL), antagomiR-146a (10 μL) and normal saline (10 μL) were intrathecally injected into rats in the three groups at 1 h before injection and 12 h, 24 h, 48 h and 72 h after injection, respectively. The ankle joint swelling index, joint dysfunction index and joint inflammation index of rats in the three groups were closely monitored. After 72 h of observation, the rats were euthanized, and synovial tissues were collected from the knee joint. The expression and distribution of nuclear factor-κB (NF-κB) in synovial tissues were detected using the immunohistochemical method. Meanwhile, the expression levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay. Furthermore, the mRNA and protein expression levels of TLR4 and MyD88 were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively., Results: No statistically significant differences in the joint swelling index, joint dysfunction index, joint inflammation index, TLR4 and MyD88 and related inflammatory factors were found between the NC group and antagomiR-146a group. Compared with the NC group, agomiR-146a group showed markedly reduced ankle joint swelling index (p<0.05). Meanwhile, joint landing behavior and inflammatory swelling were significantly relieved in the agomiR-146a group (p<0.05). The mRNA and protein expression levels of TLR4 and MyD88 were remarkably decreased as well (p<0.05). Furthermore, the expression and distribution of NF-κB in synovial tissues of agomiR-146a group was markedly reduced when compared with the NC group (p<0.05). In addition, agomiR-146a group exhibited significantly lower expression levels of inflammatory factors (TNF-α, IL-1 and IL-6) in synovial tissues (p<0.05)., Conclusions: MiR-146a alleviates joint inflammation of acute arthritis in rats through the TLR4/MyD88/NF-κB signaling pathway, which may become a new therapeutic target.

Objective: To investigate the correlation of serum vitamin A, D, and E levels with a recurrent respiratory infection (RRI) in children., Patients and Methods: The medical records of 422 children with RRI (a study group) in Cangzhou Central Hospital from January 2015 to December 2018 were retrospectively analyzed (the study group was divided into an active group and a stable group). Further 100 healthy children who underwent physical examination at the same time were enrolled as a control group. High-performance liquid chromatography (HPLC) was used to determine vitamin A, D, and E levels, so as to analyze their differences between the groups., Results: Vitamin A, D, and E in the active and stable groups were significantly lower than those in the control group (p < 0.001); in the active group they were significantly lower than those in the stable group (p < 0.001). According to partial correlation analysis, in children with active RRI, vitamin A was respectively positively correlated with vitamin D (r=0.945, p < 0.001), and vitamin E (r=0.988, p < 0.001). Moreover, vitamin E was positively correlated with vitamin D (r=0.959, p < 0.001)., Conclusions: The deficiency of vitamin A, D, and E is positively correlated with the disease activity of children with RRI. Therefore, the supplement of vitamin A, D, and E through dietary adjustment is beneficial to the rehabilitation of the children.

Background: microRNA-139 (miR-139) is dysregulated in various types of tumors and plays a key role in carcinogenesis. miR-139 may be used as a diagnostic and prognostic biomarker of cancers. However, the data from the literature are not consistent. The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors., Data Sources: PubMed, Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included. We used Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to further validate this meta-analysis., Results: Eight individual studies from seven articles were included. Pooled analyses showed that low miR-139 expression was related to worse overall survival (OS) [hazard ratio (HR) = 2.27; 95% confidence intervals (CI): 1.74-2.95; P < 0.001] in solid tumors, including hepatocellular carcinoma (HCC) and glioblastoma multiforme (GBM), consisting with the results of TCGA. However, our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon; whereas for CRC patients, high miR-139 expression predicted poor RFS, which was in good accordance with TCGA results. The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues. Decreased miR-139 expression was also significantly correlated with poor differentiation grade (OR = 3.57; 95% CI: 1.44-8.85; P = 0.006). However, the combined data indicated that no associations between miR-139 expression and the following parameters such as age (pooled OR = 1.50; 95% CI: 0.69-3.24; P = 0.304), gender (pooled OR = 0.92; 95% CI: 0.56-1.51; P = 0.738), tumor size (pooled OR = 1.51; 95% CI: 0.69-3.31; P = 0.298), late tumor-node-metastasis stage (pooled OR = 1.63; 95% CI: 0.99-2.68; P = 0.057) and lymph-node-metastasis (pooled OR = 0.66; 95% CI: 0.34-1.28; P = 0.222)., Conclusions: Low miR-139 expression was related to poor prognosis in HCC and GBM, which could be regarded as a potential prognostic biomarker. However, its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the predictive value of joint detection of serum amyloid A (SAA), plasma procalcitonin (PCT), and whole blood hypersensitive C-reactive protein (hs-CRP) in the diagnosis and efficacy of neonatal septicemia., Patients and Methods: A total of 195 cases of neonatal septicemia patients admitted to our hospital from March 2013 to May 2017 were selected as observation group, and 100 healthy newborns in the same period were selected as control group. Before treatment, all newborns were detected with enzyme-linked immunosorbent assay (ELISA) for serum SAA, PCT, and hs-CRP three indicators respectively, and differences between expressions of PCT, HS-CRP, SAA in the serum of children (effective group) who improved after treatment and patients in ineffective group were observed., Results: Three indexes of SAA, PCT, and hs-CRP in study group were significantly higher than those in control group before treatment, while three indexes of SAA, PCT, and hs-CRP in effective group were significantly lower than those in ineffective group after treatment, with statistical significance (p<0.05). By drawing the ROC curve, it was found that the AUC area, specificity, and sensitivity of joint detection were better than those of the single item detection., Conclusions: Joint detection of SAA, PCT, and hs-CRP has high diagnostic value in neonatal septicemia and is worthy of clinical application.

We have achieved significant enhancement of gene delivery into livers of large animals using ultrasound (US)-targeted microbubble (MB) destruction methods. An infusion of pGL4 (encoding a luciferase reporter gene) plasmid DNA (pDNA) and MBs into a portal-vein segmental branch of a porcine liver was exposed to US for 4 min. Therapeutic US induced cavitation of MBs to temporarily permeabilize the vascular endothelium and cell membranes, allowing entry of pDNA. We obtained a 64-fold enhancement in luciferase expression in pig livers compared to control without US using an unfocused, dual-element transducer (H105, center frequency [f c ] = 1.10 MHz) at 2.7 MPa peak negative pressure (PNP). However, input electrical energy was limited, and modified transducers were designed to have spherical (H185A, f c  = 1.10 MHz) or cylindrical foci (H185B, f c  = 1.10 MHz; H185D, f c  = 1.05 MHz) to enhance PNP output. The revised transducers required less electrical input to achieve 2.7 MPa PNP compared to H105, thereby allowing PNP outputs of up to 6.2 MPa without surpassing the piezo-material limitations. Subsequently, luciferase expression significantly improved up to 9,000-fold compared to controls with minor liver damage. These advancements will allow us to modify our current protocols toward minimally invasive US gene therapy.

Background: Nonalcoholic fatty liver disease (NAFLD), is currently a worldwide health problem. None of the existing treatment medications had got a satisfactory effect. Hua Tan Qu Shi (HTQS) decoction is a Chinese herbal formula, which has been used clinically to treat NAFLD for years. However, the underlying mechanisms are still unclear., Methods: High-fat diet (HFD) induced non-alcoholic fatty liver disease rats treated with or without HTQS decoction by gavage for 10 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups: the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-15006402., Competing Interests: Conflicts of interest: None declared.

SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. A recent research has now revealed the role of SUMO1 in cardiac disorders. Studies have evidenced that failing heart induces SUMO2/3 conjugation. Moreover, increased SUMO2/3- dependent modification has been observed to result in congestive heart disease such as cardiac hypertrophy by promoting cardiac cell death. Also, few recent studies have confirmed the role of SUMOylation in cardiac protein degradation. On the other hand, over-expression of SENP5, SUMO2/3-specific deconjugation enzyme has been observed to result in dilated cardiomyopathy or cardiac failure. So, the present review article would enlighten the latest updates about SUMOylation and associated factors during cardiac disorders.

Manipulation of biofilm formation in Shewanella is beneficial for application to industrial and environmental biotechnology. BpfA is an adhesin largely responsible for biofilm formation in many Shewanella species. However, the mechanism underlying BpfA production and the resulting biofilm remains vaguely understood. We previously described the finding that BpfA expression is enhanced by DosD, an oxygen-stimulated diguanylate cyclase, under aerobic growth. In the present work, we identify FlrA as a critical transcription regulator of the bpfA operon in Shewanella putrefaciens CN32 by transposon mutagenesis. FlrA acted as a repressor of the operon promoter by binding to two boxes overlapping the -10 and -35 sites recognized by σ 70 DosD regulation of the expression of the bpfA operon was mediated by FlrA, and cyclic diguanylic acid (c-di-GMP) abolished FlrA binding to the operon promoter. We also demonstrate that FlhG, an accessory protein for flagellum synthesis, antagonized FlrA repression of the expression of the bpfA operon. Collectively, this work demonstrates that FlrA acts as a central mediator in the signaling pathway from c-di-GMP to BpfA-associated biofilm formation in S. putrefaciens CN32., Importance: Motility and biofilm are mutually exclusive lifestyles, shifts between which are under the strict regulation of bacteria attempting to adapt to the fluctuation of diverse environmental conditions. The FlrA protein in many bacteria is known to control motility as a master regulator of flagellum synthesis. This work elucidates its effect on biofilm formation by controlling the expression of the adhesin BpfA in S. putrefaciens CN32 in response to c-di-GMP. Therefore, FlrA plays a dual role in controlling motility and biofilm formation in S. putrefaciens CN32. The cooccurrence of flrA, bpfA, and the FlrA box in the promoter region of the bpfA operon in diverse Shewanella strains suggests that bpfA is a common mechanism that controls biofilm formation in this bacterial species., (Copyright © 2017 American Society for Microbiology.)

Objective: To explore the correlation between GDF15, MMP7 and gastric cancer and its prognosis., Patients and Methods: Thirty-six cases of gastric cancer admitted to our hospital from February 2014 to February 2015 were included in the observation group. Thirty-two healthy people were selected during the same period as the control group. The levels of MMP7 and GDF15 mRNA in the observation group before and after treatment and in the control group were detected by fluorescence quantitative PCR. The expressions of GDF15 and MMP7 proteins were detected by enzyme-linked immunosorbent assay and Western-blotting analysis. The expression of GDF15 and MMP7 in gastric carcinoma were tested by immunohistochemistry assay., Results: Compared with the control group, the levels of GDF15 and MMP7mRNA in the observation group were significantly increased in gastric cancer tissue before treatment (p<0.05). After treatment, there was no significant difference in the expressions of GDF15 and MMP7 mRNA in patients with significant improvement and the control group (p>0.05). Immunohistochemistry and Western blot results found that levels of GDF15 and MMP7 proteins in the observation group before treatment (14.28±1.03: 9.06±0.82 g/l) were significantly higher than that in the control group (1.05±0.21; 0.94±0.12 g/l). And there were no significant differences between patients with significant improvement (1.64±0.18; 1.03±0.22 mg/l) and the control group (p>0.05), while the levels in patients with no significant improvement (12.04±1.01; 8.21±0.65 mg/l) were significantly higher than that in the control group. Immunohistochemical results showed that the number of GDF15 and MMP7 positive cells in patients with significant improvement (10.32%; 9.01%) were significantly lower than that before treatment or in patients with no significant improvement (85.43%; 90.27%)., Conclusions: There were significant correlations between GDF15, MMP7 and the incidence of gastric cancer. Levels of GDF15 and MMP7 in patients were significantly correlated with the degree of rehabilitation after treatment.

Objective: To observe the effect of moxibustion stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on pathological changes of myocardium and the expression of myocardial myeloid differentiation factor 88 (MyD 88) protein and Caspase 3 mRNA in chronic heart failure (CHF) rats, so as to explore its mechanism underlying improvement of CHF., Methods: SD male rats were randomly divided into normal ( n =9), model ( n =8), moxibustion ( n =8), medication ( n =8) and moxibustion + medication ( n =8) groups. In addition, the other 6 rats (3/normal and 3/model groups) were used for measuring cardiac ventricle weight and H.E. stain. The CHF model was made by intraperitoneal injection of Adriamycin (ADR, from 1 to 4 mg/kg, once every other day for 15 days). Mild moxibustion was applied to bilateral BL13 and BL15 for 15 min, once daily for 3 weeks. Rats of the medication group were treated by Captopril (gavage) for 3 weeks. The expression of myocardial Caspase 3 mRNA and MyD 88 protein of the left ventricle was determined by quantitative real time-PCR and Western blot, respectively., Results: In comparison with the normal group, the myocardial damage (cell swelling, cytoplasma vaculation, and disordered arrangement, rupture and lysis of some cardiac muscle fibers), and the expression levels of myocardial MyD 88 protein and Caspase 3 mRNA were obviously increased in the model group( P <0.01). After the interventions, the myocardial damage was relatively milder, and the expression of myocardial MyD 88 protein and Caspase 3 mRNA were significantly down-regulated in the moxibustion, me-dication and moxibustion+medication groups in comparison with the model group( P <0.05). No significant differences were found among the 3 treatment groups in the expression levels of MyD 88 protein and Caspase 3 mRNA( P >0.05)., Conclusions: Moxibustion intervention can suppress CHF induced up-regulation of expression of myocardial MyD 88 protein and Caspase 3 mRNA in rats, which may contribute to its effect in relieving myocardial injury.

Using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanisms of acupuncture therapy attracts an increasing attention nowadays. In the present article, the authors make a brief analysis on the progresses of researches about the intra-brain responses of acupuncture stimulation following collecting original research papers with key words of "acupuncture","fMRI" and "magnetic resonance imaging" in PubMed and CNKI databases from January 2003 to December 2014. As a result, a total of 253 original research articles were collected. We found that:1) in the past 10 years, the amount of fMRI studies on acupuncture is growing; 2) most of these studies (183) are conducted in healthy subjects, and fewer studies (44) conducted in patients with problems of neurology, psychonosology, gastroenterology, circulation system, pediatrics, myopia and dermatology, or with pain; 3)a larger population of studies are designed to reveal the specificity of responses of acupuncture point stimulation, and fewer focus on analyzing the regularities of acupuncture points combination. The authors suggest that the coming acupuncture-neuroimaging studies need to expand the research ranges or contents, and improve experimental designs, data analysis and quality control (for example, reducing differences of baseline data, age span, psychological state, etc., and increasing sample size, etc).

Galectin-1 is a member of carbohydrate-binding proteins and plays critical roles in tumor growth and progression. It has been reported that galectin-1 is upregulated in human hepatocellular carcinoma (HCC) and facilitates HCC cell migration and invasion. In this study, the authors aimed to explore the effects of the knockdown of galectin-1 on HCC cell survival and sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Human HCC cells were transfected with galectin-1-targeting small interfering RNA (siRNA) with or without 100 ng/mL TRAIL treatment and tested for apoptosis and gene expression changes. Cotransfection of Bcl-2- and survivin-expressing plasmids with galectin-1 siRNA was done, before TRAIL exposure, cell viability, and apoptosis were assessed. The authors found that siRNA-mediated downregulation of galectin-1 caused apoptosis in HCC cells, which was coupled with reduced Bcl-2 and survivin and increased Bax expression. Overexpression of Bcl-2 and survivin significantly blocked galectin-1 silencing-induced apoptosis of HCC cells. Knockdown of galectin-1 significantly enhanced TRAIL cytotoxicity against HCC cells, as determined by the MTT assay. Moreover, galectin-1 downregulation significantly induced apoptosis in TRAIL-treated HCC cells. Such effects were almost completely counteracted by the enforced expression of Bcl-2 and survivin. Taken together, these data first show that galectin-1 downregulation induces apoptosis in and augments TRAIL cytotoxicity to HCC cells largely through regulation of Bcl-2 and survivin expression. These findings provide a rationale for preclinical and clinical evaluation of targeting galectin-1 for improving TRAIL-based therapy against HCC.

Background: To use high resolution MRI lymphography to characterize altered tumor-draining lymph node (TDLN) lymph drainage in response to growth of aggressive tumors., Methods: Six mice bearing B16-F10 melanomas in one rear footpad were imaged by 3.0 Tesla (T) MRI before and after subcutaneous injection of Gadofosveset trisodium (Gd-FVT) contrast agent into both rear feet. Gd-FVT uptake into the left and right draining popliteal LNs was quantified and compared using Wilcoxon signed-rank test. Fluorescent dextran lymphography compared patterns of LN lymph drainage with the pattern of immunostained lymphatic sinuses by fluorescence microscopy., Results: TDLNs exhibited greater Gd-FVT uptake than contralateral uninvolved LNs, although this difference did not reach significance (P < 0.06). Foci of contrast agent consistently surrounded the medulla and cortex of TDLNs, while Gd-FVT preferentially accumulated in the cortex of contralateral LNs at 5 and 15 min after injection. Fluorescent dextran lymphography confirmed these distinct contrast agent uptake patterns, which correlated with lymphatic sinus growth in TDLNs., Conclusion: 3.0T MRI lymphography using Gd-FVT identified several distinctive alterations in the uptake of contrast agent into TDLNs, which could be useful to identify the correct TDLN, and to characterize TDLN lymphatic sinus growth that may predict metastatic potential., (© 2014 Wiley Periodicals, Inc.)

Two experiments were conducted to screen microorganisms with aflatoxin B1 (AFB1 ) removal potential from soils and to evaluate their ability in reducing the toxic effects of AFB1 in ducklings. In experiment 1, we screened 11 isolates that showed the AFB1 biodegradation ability, and the one exhibited the highest AFB1 removal ability (97%) was characterized and identified as Cellulosimicrobium funkei (C. funkei). In experiment 2, 80 day-old Cherry Valley ducklings were divided into four groups with four replicates of five birds each and were used in a 2 by 2 factorial trial design, in which the main factors included administration of AFB1 versus solvent and C. funkei versus solvent for 2 weeks. The AFB1 treatment significantly decreased the body weight gain, feed intake and impaired feed conversion ratio. AFB1 also decreased serum albumin and total protein concentration, while it increased activities of alanine aminotransferase and aspartate aminotransferase and liver damage in the ducklings. Supplementation of C. funkei alleviated the adverse effects of AFB1 on growth performance, and provided protective effects on the serum biochemical indicators, and decreased hepatic injury in the ducklings. Conclusively, our results suggest that the novel isolated C. funkei strain could be used to mitigate the negative effects of aflatoxicosis in ducklings., (© 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Objective: To study the diagnostic value and influencing factors for amplitude-integrated EEG (aEEG) in brain injury in preterm infants., Methods: One hundred and sixteen preterm infants with a gestational age (GA) between 27 weeks and 36(+6) weeks were enrolled as subjects. The aEEG scores of all preterm infants were obtained within 6 hours after birth. According to the diagnostic results, the 116 preterm infants were divided into two groups: brain injury (n=63) and non-brain injury (n=53). The risk factors for brain injury were evaluated using logistic regression analysis. According to the aEEG results, the 116 preterm infants were divided into two groups: normal aEEG (n=58) and abnormal aEEG (n=58). The influencing factors for aEEG results in preterm infants were determined using univariate analysis., Results: The brain injury group had a significantly higher rate of abnormal aEEG than the non-brain injury group (83% vs 11%; P<0.05). The infants in the brain injury group from two different GA subgroups (27-33(+6) weeks and 34-36(+6) weeks) had significantly lower aEEG scores than the non-brain injury group from corresponding GA subgroups (P<0.01). Logistic regression analysis showed that low GA (<32 weeks), low birth weight (<1 500 g), abnormal placenta, fetal membranes, and umbilical cord, and hypertension during pregnancy were high-risk factors for brain injury (P<0.05). There were significant differences in GA, birth weight, abnormal placenta, fetal membranes, and umbilical cord, and hypertension during pregnancy between the normal and abnormal aEEG groups (P<0.05)., Conclusions: The risk factors for brain injury are consistent with the influencing factors for aEEG results in preterm infants, suggesting that aEEG contributes to the early diagnosis of brain injury.

miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA molecules with 20-24 nucleotides (nt) in length that function as post-transcriptional modulators of gene expression in eukaryotic cells. Functional studies have demonstrated that plant miRNAs are involved in the regulation of a wide range of plant developmental processes. To date, however, no research has been carried out to study the expression profiles of miRNAs in Gossypium raimondii, a model cotton species. We selected 16 miRNAs to profile their tissue-specific expression patterns in G. raimondii four different tissues, and these miRNAs are reported to play important roles in plant growth and development. Our results showed that the expression levels of these miRNAs varied significantly from one to another in a tissue-dependent manner. Eight miRNAs, including miR-159, miR-162, miR-164, miR-172, miR-390, miR-395, miR-397, and miR-398, exhibited exclusively high expression levels in flower buds, suggesting that these miRNAs may play significant roles in floral development. The expression level of miR-164 was relatively high in shoots beside flower buds, implying that the function of miR-164 is not only limited to floral development but it may also play an important role in shoot development. Certain miRNAs such as miR-166 and miR-160 were extremely highly expressed in all of the four tissues tested compared with other miRNAs investigated, suggesting that they may play regulatory roles at multiple development stages. This study will contribute to future studies on the functional characterization of miRNAs in cotton.

Cardiovascular disease (CVD) is the leading cause of death, irrespective of socioeconomic status, ethnic background and sex. Despite the considerable progress in the treatment, the complex pathophysiology underlying CVD is still not clear. In past few years, genetic approaches including epigenetics and personalized medicine initiated a new way of treating CVD. Epigenetics refers to the non-DNA sequence related heritable changes in gene expression and its role in understanding and treating coronary artery disease, heart failure, and cardiac hypertrophy is currently recognized as an important player. Histone acetylation, deactylation, DNA methylation and histone methylation are different mechanisms of epigenetic modifications. Cardiac Hypertrophy is linked with histone acetylation and the activity of histone acetyltransferases (HATs) has a positive role in cardiac hypertrophy. Altered DNA methylation, miRNA activity have been shown to be associated with atherosclerosis. It is documented that re-expression of certain fetal genes in the adult heart contributes to the development of heart failure syndrome, which is often associated with pathological cardiac remodeling comprising of changes in heart mass, size and shape. Thus, it appears that approaches that counteract epigenetic changes occurring in CVD can prove to have significant therapeutic impact. However, there are no major clinical practice or therapeutics reports of epigenetics contribution in CVD, even though deacetylase inhibitors like trichostatin A were shown to have some positive effects. In this review we will present an overview of various epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA-dependent mechanisms in CVD and the novel epigenetics-based therapeutic approaches.

Cardiovascular disease (CVD), the leading cause of death, is mostly precipitated by cardiometabolic risk and chronic kidney disease (CKD). CVD and kidney disease are closely interrelated and disease of one organ cause dysfunction of the other, ultimately leading to the failure of both organs. Patients with end-stage renal disease (ESRD) are at much higher risk of mortality due to CVD. Traditional CVD risk factors viz., hypertension, hyperlipidemia, and diabetes do not account for the high cardiovascular risk in CKD patients and also standard clinical interventions for managing CVD that are successful in the general population, are ineffective to lower the death rate in CKD patients. Nontraditional factors, related to disturbed mineral and vitamin D metabolism were able to provide some explanation in terms of vascular calcification, for the increased risk of CVD in CKD. Fibroblast Growth Factor 23, a bone-derived hormone that regulates vitamin D synthesis in renal proximal tubules and renal phosphate reabsorption, has been suggested to be the missing link between CKD and CVD. Acute Kidney Injury (AKI) is strongly related to the progress of CVD and its early diagnosis and treatment has significant positive effect on the outcomes of CVD in the affected patients. Besides this, non-dialysable protein-bound uraemic toxins such as indoxyl sulfate and p-cresyl sulfate, produced by colonic microbes from dietary amino acids, appear to cause renal dysfunction. Thus, therapeutic approaches targeting colonic microbiota, have led to new prospects in early intervention for CKD patients. Intervention targets for preventing CVD events in CKD patients ideally should include control of blood pressure and dyslipidemia, diabetes mellitus, lowering proteinuria, correction of anemia, management of mineral metabolism abnormalities and life style changes including smoking cessation, decreased consumption of salt, and achievement of normal body mass index. Use of β-blockers, renin-angiotensin blockers, diuretics, statins, and aspirin are helpful in the early stages of CKD. In this review, we will address the biological, pathological and clinical relationship between CVD and CKD and their therapeutic management.

Heart failure (HF) results from the impaired ability of heart to fill or pump out blood. HF is a common health problem with a multitude of causes and affects ~30 million people worldwide. Since ageing is a major risk factor for HF and as several treatment options are currently available to prolong the patients' survival, the number of affected patients is expected to grow. Even though traditional methods of assessment have been in use for managing HF, these are limited by time consuming and costly subjective interpretation and also by their invasive nature. Comparatively, biomarkers offer an objective and biologically relevant information that in conjunction with the patients' clinical findings provides optimal picture regarding the status of the HF patient and thus helps in diagnosis and prognosis. The current gold standard biomarkers for the diagnosis and prognosis of HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP). Additional novel biomarkers (e.g., mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and galectin-3) can potentially identify different pathophysiological processes such as myocardial insult, inflammation and remodeling as the causes for the development and progression of HF. Different biomarkers of HF not only reflect the underlying mechanisms/pathways of HF and also its progression and also point specific therapy options. A multi-biomarker approach for personalized medical care is not too far fetched and such approach can greatly enhance diagnosis, prognostication, and therapy guidance for HF. In this review we describe the current status of HF biomarkers in clinical use and in laboratory research and the efforts aimed at the identification of novel biomarkers for HF.

Background: Juxtahepatic vena cava (JHC) injury is difficult to handle because of JHC injury's specific position and liver obstruction. The traditional shunt method initially appeared to be useful but ultimately failed. Simple and effective methods are needed to solve it., Methods: Firstly, the clinical data, including the computed tomography images, of 120 patients were collected. In addition, a JHC digital model was constructed based on computed tomography images. According to the digital model data, a circulation loop simulating the blood flow in the JHC was established. Secondly, we analyzed the hemodynamics of a JHC shunt with pig blood. Finally, the new shunt was designed based on the data obtained. The shunt consists of a covered stent and transfer device and was tested., Results: The JHC has a three-dimensional cylindrical structure. The mean (SD) length of the retrohepatic vena cava is 78.21 (9.83) mm, which shows correlations with the patient's age and weight (r = -0.343 and 0.271, respectively, p < 0.05). An equation is obtained as follows: retrohepatic vena cava (millimeter) = 71.23 - 0.293 × age (year) + 0.32 × weight (kilogram). The shunt diameters must be 10 mm and 12 mm to maintain the blood pressure difference Point a and Point b at approximately 3.75 mm Hg (5 cm H2O), when the flow rate is 3,000 mL/min and 5,000 mL/min, respectively. The stent graft showed effective hemostasis in tests. However, it failed when the inferior vena cava was pulled harder., Conclusion: A temporary stent graft as a new shunt for JHC injury has not been previously reported. It is a combination of both a traditional operation and a simple endovascular technique, which showed effective hemostasis in tests.

Ultrasound (US)-mediated gene delivery has emerged as a promising non-viral method for safe and selective gene delivery. When enhanced by the cavitation of microbubbles (MBs), US exposure can induce sonoporation that transiently increases cell membrane permeability for localized delivery of DNA. The present study explores the effect of generalizable MB customizations on MB facilitation of gene transfer compared to Definity®, a clinically available contrast agent. These modifications are 1) increased MB shell acyl chain length (RN18) for elevated stability and 2) addition of positive charge on MB (RC5K) for greater DNA associability. The MB types were compared in their ability to facilitate transfection of luciferase and GFP reporter plasmid DNA in vitro and in vivo under various conditions of US intensity, MB dosage, and pretreatment MB-DNA incubation. The results indicated that both RN18 and RC5K were more efficient than Definity®, and that the cationic RC5K can induce even greater transgene expression by increasing payload capacity with prior DNA incubation without compromising cell viability. These findings could be applied to enhance MB functions in a wide range of therapeutic US/MB gene and drug delivery approach. With further designs, MB customizations have the potential to advance this technology closer to clinical application., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: High temperature adversely affects quality and yield of tomato fruit. Polyamine can alleviate heat injury in plants. This study is aimed to investigate the effects of polyamine and high temperature on transcriptional profiles in ripening tomato fruit., Methods: An Affymetrix tomato microarray was used to evaluate changes in gene expression in response to exogenous spermidine (Spd, 1 mmol/L) and high temperature (33/27 °C) treatments in tomato fruits at mature green stage., Results: Of the 10101 tomato probe sets represented on the array, 127 loci were differentially expressed in high temperature-treated fruits, compared with those under normal conditions, functionally characterized by their involvement in signal transduction, defense responses, oxidation reduction, and hormone responses. However, only 34 genes were up-regulated in Spd-treated fruits as compared with non-treated fruits, which were involved in primary metabolism, signal transduction, hormone responses, transcription factors, and stress responses. Meanwhile, 55 genes involved in energy metabolism, cell wall metabolism, and photosynthesis were down-regulated in Spd-treated fruits., Conclusions: Our results demonstrated that Spd might play an important role in regulation of tomato fruit response to high temperature during ripening stage.

Three Kazal-type serine proteinase inhibitors, hcPcSPI2, hpPcSPI3, and hpPcSPI4, with complete cDNA sequences, were identified from a cDNA library of the red swamp crayfish, Procambarus clarkii. Semi-quantitative RT-PCR shows that hcPcSPI2 exists mainly in hemocytes while both hpPcSPI3 and hpPcSPI4 were detected in the hepatopancreas and the heart. Homology comparison and phylogenic analysis indicate that hpPcSPI3 and hpPcSPI4 shared high identity and formed the same group, and both of them were different from other hepatopancreas type inhibitors in crustaceans forming a large group, while hcPcSPI2 as well as other hemocyte type inhibitors belonged to another cluster. In addition, the temporal expression profiles of these three inhibitors were studied with quantitative real-time PCR and the results suggest that hcPcSPI2 and hpPcSPI3 are likely to be involved in antiviral immune response, and all these three inhibitors respond to Vibrio anguillarum challenge in different degrees. Further study was done on hcPcSPI2. Western blot demonstrates that hcPcSPI2 only exists in semigranular cells. Besides, after V. anguillarum challenge, the hcPcSPI2 protein could also be detected in cell-free hemolymph. Subsequently, the biochemical characteristics and bacteriostatic activity of hcPcSPI2 were assayed. The results indicate that hcPcSPI2 shows weak inhibitory activity against subtilisin A and trypsin, and may trigger bacteriostatic activity towards Bacillus subtilis and Bacillus thuringiensis, possessing MIC(50) of 30.4 and 25.0 microM, respectively. These studies reveal that hcPcSPI2 may also play an important role in the anti-bacterial immunity of the crayfish., (2010 Elsevier Ltd. All rights reserved.)