Deciphering the impairment of perimenopausal insomnia on visual search from a neurocognitive processing perspective.

STUDY OBJECTIVES: Perimenopausal insomnia (PMI) is associated with observable performance impairments in visual search tasks. This study examines how various cognitive processing stages contribute to search performance delays in PMI compared to healthy controls (HCs). METHODS: We recruited 76 participants diagnosed with PMI and 63 HCs. Event-related potentials (ERPs) were recorded as participants engaged in a visual search task, reporting the orientation of a color popout target within an array of ellipses. We analyzed group differences in behavioral performance and ERP components across cognitive processing stages. RESULTS: Compared to HCs, PMI patients exhibited behavioral response delays, although accuracy was not different between groups. Electrophysiological analyses revealed group differences across several ERP components. Firstly, the N1 component's amplitude increased bilaterally, suggesting enhanced visual sensory processing. Secondly, a slower and smaller N2pc indicated reduced attentional orienting. Thirdly, a decreased SPCN amplitude pointed to deficits in target discrimination. Fourthly, an increased amplitude of the stimulus-locked LRP, with unchanged latency, suggested heightened neural inputs for maintaining motor initiation speed. Fifthly, prolonged response-locked LRP latency indicated slower motor execution. Finally, these changes in ERP components, along with significant correlations between LRP components and insomnia symptoms, suggest potential neural biomarkers for PMI. CONCLUSIONS: Our findings provide high-temporal-resolution insights into the neurocognitive disruptions associated with PMI, highlighting how sleep disturbances affect cognitive processing in visual tasks. These insights enhance our understanding of PMI and contribute to discussions on neural mechanisms driving behavioral performance in various conditions.

Pulmonary actinomycosis masquerading as lung cancer.

Pulmonary actinomycosis is a rare chronic purulent granulomatous disease, which can be easily misdiagnosed as lung cancer, tuberculosis, and other diseases. However, diagnosis relies on histopathological evidence, and early diagnosis is conducive to the patient's recovery. In this study, a case of a 70-year-old man with a soft tissue density mass at the right lower lung was studied, with initial chest CT suggesting lung cancer, pulmonary actinomycosis was confirmed by subsequent pathological biopsy of lung tissues eventually. The patient responded well to antibiotics treatment. This paper is to explore the clinical characteristics of the disease, providing insight into the disease, and its diagnosis and treatment.

Electroencephalography connectome changes in chronic insomnia disorder are correlated with neurochemical signatures.

STUDY OBJECTIVES: This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions. METHODS: We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively. RESULTS: CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDR < .05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like "cognitive control" and "emotion regulation." Notably, GBC patterns were associated with neurotransmitter profiles (pspin < .05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions. CONCLUSIONS: This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID.

Clinical observation and mechanism of acupuncture on amnestic mild cognitive impairment based on the gut-brain axis: study protocol for a randomized controlled trial.

Background: Amnestic mild cognitive impairment (aMCI) is a pre-dementia condition associated with declined cognitive function dominated by memory impairment. The occurrence of aMCI is associated with the gut-brain axis. Previous studies have shown cognitive improvements in MCI after acupuncture treatment. This study evaluates whether acupuncture can produce a therapeutic effect in patients with aMCI by modulating the gut-brain axis. Methods and design: This is a prospective, parallel, multicenter randomized controlled trial. A total of 40 patients with aMCI will be randomly assigned to an acupuncture group (AG) or a waiting-list group (WG), participants in both groups will receive health education on improving cognitive function at each visit, and acupuncture will be conducted twice a week for 12 weeks in the AG. Another 20 matched healthy volunteers will be enrolled as normal control. The primary outcome will be the change in Alzheimer's Disease Assessment Scale-cognitive scale score before and after treatment. Additionally, functional magnetic resonance imaging data, faeces, and blood will be collected from each participant to characterize the brain function, gut microbiota, and inflammatory cytokines, respectively. The differences between patients with aMCI and healthy participants, and the changes in the AG and WG groups before and after treatment will be observed. Ultimately, the correlation among brain function, gut microbiota, inflammatory cytokines, and clinical efficacy evaluation in patients with aMCI will be analyzed. Discussion: This study will identify the efficacy and provide preliminary data on the possible mechanism of acupuncture in treating aMCI. Furthermore, it will also identify biomarkers of the gut microbiota, inflammatory cytokines, and brain function correlated with therapeutic effects. The results of this study will be published in peer-reviewed journals. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2200062084.

[Graduate training mode of acupuncture-moxibustion and tuina based on "three crosses and two integrations": a preliminary study].

In view of the core tasks and weak links in the training of medical graduate in the new era, based on the characteristics and development needs of the discipline, a new "three crosses and two integrations" graduate training mode of acupuncture-moxibustion and tuina is proposed, with "equal emphasis on inheritance and innovation, theory and practice" as the core, with "curriculum cross" as the basis, with "academic cross" as the connotation, and with "discipline cross" as the pathway. This new training mode focuses on the comprehensive cultivation of graduates' comprehensive abilities, aiming to achieve the training goal of "strong inheritance ability, excellent innovation ability, good practical ability and broad international perspective".

Classification of primary dysmenorrhea by brain effective connectivity of the amygdala: a machine learning study.

BACKGROUND: The amygdala plays a crucial role in the central pathogenesis mechanism of primary dysmenorrhea (PDM). However, the detailed pain modulation principles of the amygdala in PDM remain unclear. Here, we applied the Granger causality analysis (GCA) to investigate the directional effective connectivity (EC) alterations in the amygdala network of PDM patients. METHODS: Thirty-seven patients with PDM and 38 healthy controls were enrolled in this study and underwent resting-state functional magnetic resonance imaging scans during the pain-free stage. GCA was employed to explore the amygdala-based EC network alteration in PDM. A multivariate pattern analysis (MVPA)-based machine learning approach was used to explore whether the altered amygdala EC could serve as an fMRI-based marker for classifying PDM and HC participants. RESULTS: Compared to the healthy control group, patients with PDM showed significantly decreased EC from the amygdala to the right superior frontal gyrus (SFG), right superior parietal lobe/middle occipital gyrus, and left middle cingulate cortex, whereas increased EC was found from the amygdala to the bilateral medial orbitofrontal cortex. In addition, increased EC was found from the bilateral SFG to the amygdala, and decreased EC was found from the medial orbitofrontal cortex, caudate nucleus to the amygdala. The increased EC from the right SFG to the amygdala was associated with a plasma prostaglandin E2 level in PDM. The MVPA based on an altered amygdala EC pattern yielded a total accuracy of 86.84% for classifying the patients with PDM and HC. CONCLUSION: Our study is the first to combine MVPA and EC to explore brain function alteration in PDM. The results could advance understanding of the neural theory of PDM in specifying the pain-free period.

Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. RESULTS: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. CONCLUSION: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.

Opinion Dynamics Model with Bounded Confidence and the Sleeper Effect.

The evolution of opinions is a complex mechanism. The evolution of individual opinions is not only influenced by own and others but also by psychological effects. Therefore, based on the classical bounded confidence model and the sleeper effect, a new opinion evolution model is proposed in this paper. In this new opinion evolution model, we increase the opinions on every step and take into account the "discount opinions." Since mental states for human are not easy to measure, we assumed three different initial networks and carried out simulation experiments. To verify the rationality on our model, we compared the effects with and without the sleeper effect, different thresholds, and discounting opinion ratio on opinion aggregation and convergence. Finally, we found the sleeper effect can differently affect the convergence of opinions in different opinion environments.

Differences in the individual curative effect of acupuncture for obese women with polycystic ovary syndrome based on metagenomic analysis: study protocol for a randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome is a common cause of infertility and shows a high incidence in women of reproductive age. Acupuncture is an appropriate adjunctive treatment for PCOS. However, the add-on effect of acupuncture as an adjunctive treatment for obese women with PCOS has not been studied, and previous studies indicate that there are individual differences in the curative effect of acupuncture, while deeper research on the mechanism of differences in the individual curative effect of acupuncture for obese women with PCOS is still lacking. This trial aims to assess the add-on treatment efficacy of acupuncture for obese women with PCOS and to explore the role of the gut microbiome on the differences in the individual curative effect of acupuncture based on metagenomic analysis. METHODS/DESIGN: This is an open-label, randomized, controlled trial. A total of 86 obese women with PCOS will be recruited. Subjects will be randomly assigned to a study group and a control group in a 1:1 ratio, with 43 subjects in each group (10 patients from each group who meet the study criteria will participate in the metagenomic analysis). An additional 10 subjects who meet the study criteria will be recruited to a healthy control group. The study group will receive acupuncture and clomiphene citrate treatment; the control group will only receive clomiphene citrate. Acupuncture treatment will be conducted three times a week from the fifth day of menstruation or withdrawal bleeding until the start of the next menstruation, for up to three menstrual cycles. The primary outcome will be LH/FSH. The secondary outcomes will comprise biometric features, hormone biomarkers, metabolic biomarkers, inflammatory biomarkers, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and metagenomic analysis. The outcomes will be measured at baseline and post-intervention. Data will be analyzed using SPSS 19.0, and the gut microbiome will be analyzed using metagenomic analysis. DISCUSSION: In this study, we are evaluating the add-on effects of acupuncture and exploring the mechanism of the differences in the individual curative effect of acupuncture based on the gut microbiome, which may provide evidence to explain the different outcomes of different trials on acupuncture for PCOS and hopefully to provide a new aspect to study the mechanism of acupuncture's treatment effect. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029882 . Registered on 16 February 2020.

The cerebral mechanism of acupuncture for chronic insomnia with gastrointestinal disorder: protocol for a randomized controlled trial.

BACKGROUND: Many patients with chronic insomnia disorder (CID) have gastrointestinal (GI) symptoms. First-line insomnia medications do not treat GI problems. Acupuncture has a comprehensive regulative action on both CID and GI disorder and is receiving increasing attention. Recent studies indicate that both CID and GI diseases may cause abnormal brain activity. However, the neurological mechanism underlying the effect of acupuncture on such diseases is still unclear. The aim of this study is to explore the pathological mechanisms of CID with GI discomfort, as well as the main response characteristics of acupuncture treatment from multiple perspectives using multimodal magnetic resonance imaging (MRI). METHODS: A total of 60 participants with CID and GI disorders will be randomly divided into two groups (real acupuncture group and sham acupuncture group; ratio of 1:1). Patients will receive 20 sessions (five sessions per week) of real acupuncture treatment or sham acupuncture treatment. The primary outcome is the aggregate score on the Pittsburgh Sleep Quality Index. Secondary outcomes are scores on the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. Multimodal MRI scans and clinical assessments will be performed both at baseline and post-treatment. Another 30 age-, sex-, and education-matched healthy subjects will be recruited as controls and will receive MRI scans and clinical evaluations. DISCUSSION: This study aims to provide scientific evidence for the mechanism of acupuncture in treating CID with GI disorder using multimodal MRI imaging data on brain structure, function, and metabolism. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017092 (URL: http://www.chictr.org.cn/showproj.aspx?proj=27173 ). Registered on July 11, 2018.

Molecular Mechanisms of Exercise on Cancer: A Bibliometrics Study and Visualization Analysis via CiteSpace.

Objective: To analyze the research hot spots and frontiers of molecular mechanisms of exercise on cancer via CiteSpace. Method: Related publications in the Web of Science Core Collection Science Citation Index Expanded were retrieved from inception to November 27th, 2021. Then we used CiteSpace to generate network maps and identify top authors, institutions, countries, keywords, co-cited authors, journals, references and research trends. Results: A total of 1,130 related publications were retrieved. The most productive author and journal were Lee W Jones and PLOS ONE. Hanahan D and Warburg O were the most cited authors. Fudan University and Shanghai Jiao Tong University were the leading institutions, while China was the leading country. Top-cited authors and references generally focused on the epidemiology and hallmarks of cancer. Top five keywords with both high frequency and high betweenness centrality were breast cancer, aerobic glycolysis, oxidative stress, gene expression, skeletal muscle. Keyword "warburg effect" ranked first with the highest citation burst, while "inflammation", "hepatocellular carcinoma", "epithelial mesenchymal transition", and "adipose tissue" were emerging research foci. Conclusion: This study analyzed the research hot spots and frontiers of molecular mechanisms of exercise on cancer via CiteSpace. Based on the results, altered metabolism (aerobic glycolysis, insulin resistance, myokines), oxidative stress, gene expression and apoptosis were hot-research mechanisms of exercise on cancer. Emerging research foci of mechanisms were generally around inflammation, epithelial mesenchymal transition and adipokines. In addition, future studies could carry in-depth research of interactions between different mechanisms and try to elucidate the recommended doses and intensities of exercise for cancer, especially in breast, colorectal, prostate cancer and hepatocellular carcinoma.

Acupuncture for Chronic Fatigue Syndrome: An Overview of Systematic Reviews.

OBJECTIVE: To evaluate the quality of the existing studies and summarize evidence of important outcomes of meta-analyses/systematic reviews (MAs/SRs) of CFS. METHODS: Potentially eligible studies were searched in the following electronic databases from inception to 1 September, 2019: Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed and Cochrane Library. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. The methodological quality of the literature was evaluated by A Measure Tool to Assess Systematic Reviews-2 (AMSTAR-2) and the quality of the report was assessed by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The intra-class correlation coefficient was used to assess the consistency of the reviewers, with an overall intraclass correlation coefficient score of 0.967. RESULTS: Ten MAs/SRs were included. The overall conclusions were that acupuncture had good safety and efficacy in the treatment of CFS, but some of these results were contradictory. The GRADE indicated that out of the 17 outcomes, high-quality evidence was provided in 0 (0%), moderate in 3 (17.65%), low in 10 (58.82%), and very low in 4 (23.53%). The results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The PRISMA statement revealed that 8 articles (80%) were in line with 20 of the 27-item checklist, and 2 articles (20%) matched with 10-19 of the 27 items. CONCLUSION: We found that acupuncture on treating CFS has the advantage for efficacy and safety, but the quality of SRs/MAs of acupuncture for CFS need to be improved.

Acupuncture for "poor ovarian response" of women to controlled ovarian hyperstimulation: A protocol for meta-analysis and systematic review.

BACKGROUND: Poor ovarian response (POR) is a high-incidence disease of women, which cause in vitro fertilization failure. Various treatment options have been proposed for women with POR to improve their ovarian response, but with little effect. In recent years, there is a wide range of applications of acupuncture in the process of in vitro fertilization. The meta-analysis and systematic review are designed to analyze whether acupuncture is effective for patients with POR. METHODS: The following databases will be searched from inception to March 2020: Electronic databases consist of MEDLINE, EMBASE, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and Wanfang Database. Other literature resources will also be searched including clinical trial registries, key journals, and meeting records. The results of randomized controlled trials of acupuncture therapy on POR, which are published in Chinese or English, will be embedded. The primary outcome is the clinical pregnancy rate. Data identification, data selection, data extraction, and assessment of bias risk will be completed independently by 2 or more reviewers. STATA/IC 16 will be used to perform the meta-analysis. We will use the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the quality of our evidence. A systematic narrative synthesis will be provided if the quantitative analysis is not available. DISCUSSION: This study will provide the first meta-analysis and systematic review to evaluate the efficacy of acupuncture in treating POR. This protocol provides details to guide this study. CONCLUSIONS: From this review may benefit POR patients or clinical decision-makers. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020169560.

Does the Acupoint Specificity Exist? Evidence from Functional Neuroimaging Studies.

BACKGROUND: Using functional neuroimaging techniques to explore the central mechanism of acupoint specificity, the key of acupuncture theory and clinical practice, has attracted increasing attention worldwide. This review aimed to investigate the current status of functional neuroimaging studies on acupoint specificity and explore the potential influencing factors for the expression of acupoint specificity in neuroimaging studies. METHODS: PubMed database was searched from January 1st, 1995 to December 31st, 2016 with the language restriction in English. Data including basic information, methodology and study results were extracted and analyzed from the eligible records. RESULTS: Seventy-nine studies were finally enrolled. 65.8% of studies were performed in China, 73.4% of studies were conducted with healthy subjects, 77.2% of studies chose manual acupuncture as the intervention, 86.1% of studies focused on the instant efficacy and 89.9% of studies used functional magnetic resonance imaging as scanning technique. The average sample size was 16 per group. The comparison of verum acupoints and sham acupoints were the main body of acupoint specificity researches. 93.7% of studies obtained the positive results and favored the existence of acupoint specificity. CONCLUSION: This review affirmed the existence of acupoint specificity and deemed that the acupoint specificity was relative. Multiple factors such as participants, sample size, acupoint combinations, treatment courses, and types of acupoint could influence the expression of acupoint specificity.

Effect of acupuncture and its influence on cerebral activity in patients with persistent asthma: study protocol for a randomized controlled clinical trial.

BACKGROUND: Previous studies suggested that acupuncture was a promising adjunctive treatment for asthma. However, the underlying mechanism of acupuncture for asthma remains unclear. The aim of the present trial is to explore whether and how specific meridian acupuncture works in quality of life and symptomatic improvement by modulating brain function in patients with asthma. METHODS/DESIGN: This is a randomized controlled functional brain imaging trial currently being conducted in Sichuan, China. In total, 48 patients with mild to moderate persistent asthma will be recruited randomly and allocated to either of two acupuncture groups: acupuncture at the lung meridian or acupuncture at the heart meridian. The treatment period will last 4 weeks. The Asthma Quality of Life Questionnaire is the primary outcome. The Asthma Control Test, peak expiratory flow rate, forced expiratory volume in 1 s, Montreal Cognitive Assessment, Zung Self-rating Anxiety Scale, and Zung Self-rating Depression Scale will also be used to assess the clinical efficacy of different interventions. Functional magnetic resonance imaging (fMRI) will be performed to detect cerebral activity changes in each group. The clinical data and fMRI data will be analyzed between groups, then, the Pearson correlation analysis will be used to assess the association between the changes of cerebral activity features and the improvement of clinical outcomes in each group. DISCUSSION: The present study has been established on the basis of the "meridian-viscera relationship" theory of traditional Chinese medicine and the modern central mechanism of acupuncture. The results of this trial would be useful to identify the efficiency of the specific meridian acupuncture for asthma. The investigation of its central mechanism would further expand knowledge of acupuncture for asthma. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027478. Registered on 15 November 2019.

The Status of the Acupuncture Mechanism Study Based on PET/PET-CT Technique: Design and Quality Control.

PET/PET-CT is an important technique to investigate the central mechanism of acupuncture in vivo. This article collected original research papers with keywords of "Acupuncture," "PET," "PET/CT," and "Positron emission tomography" in PubMed and CNKI databases from January 2003 to December 2018. As a result, a total of 43 articles were included. Based on the literature analyses, we found that (1) reasonable arrangement of the operation process and the choice of appropriate acupuncture intervention time is conducive to a better interpretation of acupuncture-PET/PET-CT mechanism and (2) the selection of participants, sample size, acupuncture intervention, and experimental conditions would affect study results. Therefore, effective quality control is an important way to ensure the repeatability of research results.

The central mechanism of acupuncture treatment with a long-lasting effect for functional dyspepsia: study protocol for a randomized controlled trial.

BACKGROUND: The mechanism of the long-lasting effect and the relationship between the long-lasting effect and the deqi sensation, which is the key of achieving the acupuncture effect, has not been well investigated. This trial focuses on investigating the possible central mechanism of the long-lasting effect influenced by the deqi sensation. METHODS: A randomized controlled functional brain imaging trial is currently being conducted in Sichuan, China. In total 105 functional dyspepsia (FD) patients will be allocated into three groups: an acupuncture with deqi group, an acupuncture without deqi group, and a wait-list group. This trial will include a 2-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment, patients in two acupuncture groups will receive 20 sessions of acupuncture treatment with or without deqi. The Nepean Dyspepsia Index (NDI) and the short form Leeds Dyspepsia Questionnaire (SF-LDQ) will be used to evaluate the clinical efficacy of acupuncture treatment at baseline, the end of treatment, and the end of the follow-up. Functional magnetic resonance imaging (fMRI) scans will be performed to detect cerebral functional changes in 25 patients in each group at three time points mentioned above. The clinical data and fMRI data will be analyzed, respectively. Correlation analysis will be conducted to investigate the relationship between cerebral functional changes and symptom improvement. DISCUSSION: The results of this trial will allow us to compare the changes of acupuncture therapeutic effect at three time points (the baseline vs. the end of treatment vs. the end of follow-up), and investigate the potential central mechanism of the long-lasting effect influenced by acupuncture with deqi. This trial aims to re-identify the long-lasting effect of acupuncture and investigate its central mechanism, and to further explore the central influence of deqi sensation on the long-lasting effect. TRIAL REGISTRATION: Chinese Clinical Trial Registry, IDF: ChiCTR-IOR-15006523 . Registered on 5 June 2015.