Global research states and trends of micro RNA in irritable bowel syndrome: a bibliometric analysis.

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. Non-coding RNAs (ncRNAs), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People's Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncRNAs regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microRNA (miRNAs) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncRNA may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncRNAs (especially miRNAs). Our findings will help understand the role of ncRNAs in IBS and provide guidance to future studies.

Scheme optimization of acupoints compatibility and influence factors of the effect.

BACKGROUND: Acupuncture may be a clinically effective treatment for insomnia. We will perform a multicenter, large-scale, single-blinded, randomized controlled trial to compare the differences in the clinical efficacy between the use of singleacupoints and compatibilityacupoints in the treatment of primary insomnia. METHODS/DESIGN: A total of 333 participants will be randomly assigned to 2 acupoint treatment groups or 1 nonacupoint control group in a 1:1:1 ratio by a central stochastic system. The acupuncture groups are: the single acupoint group: Shenmen (HT7); and he compatibility acupoint group: Shenmen (HT7), Baihui (DU20), and Sanyinjiao (SP6). The observation period of this trial will be 10 weeks. All patients will be followed for 1 week before randomization (baseline phase). After randomization, the patients will receive 30 minutes of electro-acupuncture once per day for 5 weeks. In the fourth week after the treatment, follow-up will be performed once. The primary outcome will be the Pittsburgh sleep quality index score at 1 week before randomization and 2 and 8 weeks after randomization. The secondary outcomes will include data from sleep diaries, Athens insomnia scale scores, ShortForm-36 Health Survey scores, electroencephalogram technology results and polysomnogram) results. Patients will be required to complete a sleep diary every day during the treatment period. Patients will also undergo electroencephalogram technology and polysomnogram 1 week before randomization and 5 weeks after randomization. The other secondary outcomes will be measured 1 week before randomization and 5 and 9 weeks after randomization. DISCUSSION: This trial will be helpful in identifying whether acupuncture at compatibility acupoints is more effective than acupuncture at single acupoints. TRIAL REGISTRATION: Clinical Trials.govNCT02448602, Registered 5May 2015, https://www.clinicaltrials.gov/ct2/show/NCT02448602?term=NCT02448602&rank=1.

The effectiveness of acupoint herbal patching for functional dyspepsia: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) has gradually developed into a multiple disease of the digestive system that most patients may be accompanied by mental and emotional disorders, such as insomnia, anxiety, and depression. Acupoint herbal patching (AHP) is usually used as an alternative therapy for patients with FD. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on FD. METHODS: We will search the Cochrane Central Register of Controlled Trials, the Web of Science, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure for randomized controlled trials of FD treated by AHP from inception to June 30, 2021. The primary outcome measures contain clinical effective rate, the symptom score of FD, and secondary outcome measures consist of quality of life, incidence of adverse events, and recurrence rate. We will use RevMan V.5.3 software to analyze data. Two reviewers will evaluate the risk of bias and the quality of the studies by the Cochrane Collaboration risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation approach, separately. RESULTS: This systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom, and safety of AHP therapy for FD. CONCLUSION: The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for FD.

The effectiveness of acupoint application of traditional Chinese medicine in treating primary dysmenorrhea: A protocol for meta-analysis and data mining.

BACKGROUND: Primary dysmenorrhea (PD) is a functional disease of the female reproductive system, which has adverse effects on patients' physical and mental health and quality of life. At present, acupoint application of traditional Chinese medicine (TCM) as adjuvant therapy is undergoing clinical trials in different medical centers. However, there is no systematic review or meta-analysis to evaluate the efficacy of acupoint application of TCM in the treatment of PD. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: All randomized controlled trials related to acupoint catgut embedding therapy on PD will be searched in the following electronic databases: Cochrane Central Registry of controlled trials, PubMed, Wed of Science, EMBASE, Science Net, China Biomedical Literature Database, China Science Journal Database, China National Knowledge Infrastructure and Wan-Fang Database, from inception to May, 2021 were searched without language restrictions. The primary outcomes contain visual analog score, The Cox Menstrual Symptom Scale, while the secondary outcomes consist of adverse events and the recurrence rate. Two reviewers will independently perform data selection, data synthesis, and quality assessment. Data meeting the inclusion criteria will be extracted and analyzed by Revman v.5.3 software. Two reviewers will evaluate the study using the Cochrane collaborative bias risk tool. We will use the scoring method to assess the overall quality of the evidence supporting the main results. We will also use Spass software (version 19.0) for complex network analysis to explore the potential core prescription of acupoint application of traditional Chinese medicine in the treatment of PD. RESULTS: This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of PD, and effective prescriptions of acupoint application for patients with PD. CONCLUSION: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PD.PROSPERO registration number: CRD 42021244357.

The effectiveness of acupoint herbal patching for functional constipation: Protocol for a meta-analysis and data mining.

BACKGROUND: Functional constipation is a common functional problem of the digestive system that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of acupoint herbal patching on functional constipation. There is also a lack of systematic evaluation and analysis of acupoints and herbs. METHODS: We will search the following 8 databases from their inception to November 15, 2020, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation. RESULTS: This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of functional constipation, and effective prescriptions of acupoint herbal patching for patients with functional constipation. CONCLUSION: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint herbal patching for patients with functional constipation. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42020193489.

Effectiveness and cerebral responses of multi-points acupuncture for primary insomnia: a preliminary randomized clinical trial and fMRI study.

BACKGROUND: Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism. METHODS: A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests. RESULTS: The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience. CONCLUSIONS: Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy. TRIAL REGISTRATION: This trial has been registered on the U.S. National Library of Medicine (https://clinicaltrials.gov) ClinicalTrials.gov Identifier: NCT02448602 . Registered date: 14/04/2015.

Efficacy of compatible acupoints and single acupoint versus sham acupuncture for functional dyspepsia: study protocol for a randomized controlled trial.

BACKGROUND: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD). METHODS: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019.

[Review on application of neural tracing technique to experimental research of acupuncture].

OBJECTIVE: To collect literatures on the application of neural tracing technique in experimental acupuncture research, and summarize its application status in acupoints, meridians and Zang-fu organs. METHODS: We collected papers published from databases of CNKI (1979-2017), Wan-Fang (1990-2017), VIP (1989-2017) and PubMed(1997-2017)by using keywords of "neural tracing technique" "neuroanatomic tracing" "neural tracers" and "acupuncture" "electroacupuncture" "auricular acupuncture" "eye acupuncture" "meridians" "acupuncture points" "acupoint injection", and made a summary about the current state of application of neural tracing technique in the fields of acupoint, meridian and Zang-fu organs (viscera). RESULTS: A total of 94 articles were collected, the most commonly used neural tracers were horseradish peroxidase and cholera toxin subunit B. The experimental animals used were rat, rabbit, cat, monkey, etc., and injection site was acupoint. After the injection of neural tracers, the survival time of animals was range from 1 day to 12 weeks, and the labelled tissues included neurons and nerve fibers of the sensory, motor, and autonomic systems. The outcomes of neural labeling mainly revealed the segmental pattern, neuroanatomical connection (neural pathways/circuits) and chemical features (shown by immunohistochemical staining) of neurons and nerve fibers innervating both the acupoints and visceral organs, suggesting their involvement in the effect of acupuncture and moxibustion treatment. CONCLUSION: This application of neural tracing technology help us understand the under-lying mechanisms of acupuncture and moxibustion interventions from different perspectives of neural pathways/circuits and related chemical properties, which also lays a greater role for this technology in future experimental acupuncture research.

NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage.

Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.

[Professor WANG Fuchun's experience in the acupoint selection of clinical treatment with acupuncture and moxibustion].

Professor WANG Fuchun's experience in the acupoint selection of clinical treatment with acupuncture and moxibustion was summarized. The main acupoints are selected by focusing on the chief symptoms of disease, the supplementary points are selected by differentiating the disorders. The acupoints are modified in terms of the changes of sickness. The effective acupoints are selected flexibly in accordance with the specific effects of points. The summary on the acupoint selection reflects professor WANG Fuchun's academic thoughts and clinical experience and effectively instructs the clinical practice of acupuncture and moxibustion.

[Analysis of Compatibility Laws for Acupoint Selection of Acupuncture in Treating Diabetic Gastroparasis].

OBJECTIVE: To summarize and analyze the compatibility laws for acupoint selection of acupuncture in treating diabetic gastroparasis (DGP) in modern literatures of clinical researches. METHODS: Retrieved were literatures related to treating DGP by acupuncture or acupuncture combined other therapies from PubMed, CNKI, and WF from 1982 to 2014. Analyzed were frequency of acupoint use, meridians selected acupoints belonged to, regions selected, association laws of selected compatible acupoints. RESULTS: Retrieved were 35 with compatibility frequencies more than 15 listed as follows: compatibility frequency of Zusanli (ST36) and Zhongwan (CV12) was 33 (94.29%); compatibility frequency of Zusanli (ST36) and Neiguan (PC6) was 23 (65.71%), compatibility frequency of Zhongwan (CV12) and Neiguan (PC6) was 22 (62.86%), compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Neiguan (PC6) was 22 (62.86%); compatibility frequency of Zusanli (ST36) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zhongwan (CV12) and Sanyinjiao (SP6) was 16 (45.71%); compatibility frequency of Zusanli (ST36), Zhongwan (CV12), and Sanyinjiao (SP6) was 15 (42.86%). Meridians selected acupoints belonged to were sequenced as Foot Yangming Stomach channel, Ren channel, Foot Taiyang Bladder channel, and so on. Acupoints selected were mainly in lower limbs, chest and abdomen, waist and back. The compatibility of Zusanli (ST36) and Zhongwan (CV12) was the most often used with the highest frequency. CONCLUSIONS: The compatibility laws for acupoint selection of acupuncture in treating DGP were mainly dominated as upper-lower selection, three regions selection, local selection, anterior-posterior selection. The compatibility laws for acupoint selection of acupuncture along meridians were mainly dominated as the convergence points and exterior-interior meridian points.

[Experience summary of professor WANG Fuchun's "Zhenjing Anshen" acupuncture method for insomnia].

The experience of "Zhenjing Anshen" acupuncture method originally created by professor WANG Fuchun for treatment of insomnia was introduced in this paper. From aspects of insomnia pathogenesis, theoretical foundation, characteristics of acupoint selection, needing methods, needing time, etc., the experience of Professor WANG Fuchun for treatment of insomnia was explained. The "Zhenjing Anshen" acupuncture method proposed, for the first time, "new three layers" method of acupoint selection, including Sishencong (EX-HN 1), Shenmen (HT 7), Sanyinjiao (SP 6). This method presents the principles of acupoint selection along meridian, acupoint selection based on essence-qi-spirit, harmony of yin and yang. The acupuncture manipulation is emphasized, and treating time (the period of the day from 3 pm to 5 pm) is focused on; acupoint selection is simple but essential, and acupoint combination is scientific, which receives notable therapeutic effect in clinic.

[Exploration and analysis on the "similar-indication acupoints"].

The concept, connotation and extension of "similar-indication acupoints" which is proposed by Professor WANG Fuchun are introduced in this paper. It is noted that "similar-indication acupoints" is one category of acupoints that hass similar effects for one symptom or disease, which is the basic element for acupoints compatibility, while acupoint compatibility is the foundation of acupuncture acupoints prescription. The proposal and application of "similar-indication acupoints" has provided a new method for the transition from specificity study to generality study, also lay a solid theoretical foundation for acupoints compatibility search.

[The expression of calcitonin gene-related peptide in the sensory and motor neurons associated with "Hegu" (LI 4) in the rat].

OBJECTIVE: To investigate the chemical expression of the primary sensory and motor neurons associated with "Hegu" (LI 4) area by using neural tracing and fluorescent immunohistochemical techniques. METHODS: A total of 4 SD rats were used in the present study. After anesthesia, the rats received microinjection of 5 microL of Alexa Fluor 594 conjugated cholera toxin subunit B (AF 594-CTB) into the right "Hegu" (LI 4) area for observing the distribution of the related primary sensory neurons in dorsal root ganglia (DRGs) and motor neurons in the spinal cord (C 1 - C 5). Three days after the microinjection, the rats were anesthetized and transcardiacally perfused with 4% paraformaldehyde, followed by routine section of the DRGs and spinal cord tissues. The labeled neurons were observed by light microscope and their chemical characteristics determined by calcitonin gene-related peptide (CGRP) fluorescent immunohistochemical method. RESULTS: All the AF 594-CTB labeled neurons in DRGs and spinal cord were located on the side of the tracer injection. The labeled sensory neurons distributed in DRGs of cervical (C) 5 to thoracic (T) 1 segments with a high concentration in C 7 DRG in which 73.5% sensory neurons were shown to be CGRP-positive. The labeled motor neurons were found to be in the dorsolateral region of the spinal anterior horns from C 6 to T 1 segments, with a high concentration at C 8 in which 100% motor neurons were shown to be CGRP-positive. CONCLUSION: Acupoint LI 4 is innervated by sensory neurons from DRGs of C 5 - T 1 and motor neurons from anterior horns of the same segmental spinal cord in rats. Among them, 73.5% of the sensory neurons and 100% of the motor neurons are CGRP-positive, suggesting an involvement of CGRP in acupuncture stimulation-LI 4 induced therapeutic effects.

[Segmental and regional distribution of neurons and their axonal projection associated with acupoint "yongquan" (KI 1) in the rat: cholera toxin subunit B method].

OBJECTIVE: To observe the distribution of neurons and their axonal projection associated with "Yongquan" (KI 1) area by neural tracing technique with cholera toxin subunit B (CTB). METHODS: A total of 5 microL of 1% CTB solution was injected into the front central part of hind foot plantar (corresponding to the KI 1 region in the human body) using a Hamilton microsyringe. After 3 survival days, the rats were deeply anesthetized and transcardically perfused for collecting the dorsal root ganglia (DRGs), spinal cord and brain tissues. Following fixing in 4% paraforldehyde containing phosphate buffer solution (PBS) and incubation in PBS containing 25% glucose solution, the aforementioned tissues were sectioned to be stained with immunofluorescence or immunohistochemistry for revealing the labeled sensory neurons and their tansganglionic projection and motor neurons. RESULTS: All the labeled neurons (sensory and motor neurons) and transganglionic axonal projection appeared ipsilaterally to the injection side. The labeled sensory neurons were located in the DRGs of lumbar 3-5 segments (L 3-L 5) with a higher concentration at L 4, while motor neurons distributed in the dorsolateral portion of spinal ventral horn from L 3 to L 6 with a higher concentration at L 5. In addition, transganglionic axonal projections were found to situate in the medial part of laminae III - IV from L 3 to L 5, as far as in the gracile nucleus. CONCLUSION: Acupoint KI 1 area is innervated by sensory neurons in L 3-L 5 DRGs and motor neurons from the dorsolateral ventral horns of L 3-L 6. The axonal projection of the primary sensory neurons distributes in the medial part of laminae III - IV of L 3-L 5 and gracile nucleus, respectively.

Specificity of Sensory and Motor Neurons Associated with BL40 and GB30 in the Rat: A Dual Fluorescent Labeling Study.

The purpose of this study is to investigate the specific innervations on "Weizhong" (BL40) and "Huantiao" (GB30) by using a dual neural tracing technique. After Alexa Fluor 488 and 594 conjugates of cholera toxin subunit B (AF488/594-CTB) were, respectively, injected into BL40 and GB30 in the same rat, the labeled sensory and motor neurons were examined in the rat's dorsal root ganglia (DRGs) and spinal cord at thoracic (T) and lumbar (L) segments with a laser scanning confocal microscope. In the cases of BL40 injection, AF488-CTB labeled sensory and motor neurons were located in L2-6 DRGs and on the mediolateral part of spinal ventral horn from L3 to L5 segments, respectively. By contrast, in the cases of GB30 injection, AF594-CTB labeled sensory and motor neurons were distributed in T13-L6 DRGs and on the anterolateral part of spinal ventral horn from L1 to L5 segments, respectively. These results indicate that the sensory and motor neurons associated with BL40 and GB30 are located in different spinal segments and regions in the nervous system, providing the neuroanatomical evidence to serve the specificity of acupoints.

Neuroanatomical basis for acupuncture point PC8 in the rat: neural tracing study with cholera toxin subunit B.

OBJECTIVES: This study was performed to investigate the innervations related to acupuncture point PC8 in rats using a neural tracing technique. METHODS: After 6 µL of 1% cholera toxin subunit B (CTB) was injected into the site between the second and third metacarpal bone in rats, a corresponding site to acupuncture point PC8 in the human body, CTB labelling was examined with immunofluorescence and immunohistochemistry in the dorsal root ganglia (DRG), spinal cord and brainstem. RESULTS: All CTB labelling appeared on the ipsilateral side of the injection. The labelled sensory neurons distributed from cervical (C)6 to thoracic (T)1 DRG, while the labelled motor neurons were located on the dorsolateral part of the spinal ventral horn ranging from the C6 to T1 segments. In addition, the transganglionically-labelled axonal terminals were found to be dense in the medial part of laminae 3-4 from C6 to the T1 spinal dorsal horn, as far as in the cuneate nucleus. CONCLUSIONS: These results indicate that sensory and motor neurons associated with PC8 distribute in a distinct segmental pattern. The sensory information from PC8 could be transganglionically transported to the spinal dorsal horn and cuneate nucleus.