Effects of acupuncture on functional gastrointestinal disorders: special effects, coeffects, synergistic effects in terms of single or compatible acupoints.

OBJECTIVE: To investigate how the "special effect"/ "coeffect"/"synergistic effect" can achieve a positive result using an "acupuncture prescription" for functional gastrointestinal disorders (FGIDs) in clinical practice, based on the characteristics of single/compatible acupoints and acupuncture techniques. METHODS: According to the search strategy, we searched six electronic bibliographic databases and provided a summary for this overview. RESULTS: A large body of evidence has shown that acupuncture has positive effects in the treatment of FGIDs. However, the "prescription" intervention involved different single acupoints, compatible acupoints and acupoints based on expert consensus. CONCLUSIONS: The core acupoints, including Tianshu (ST25), Zusanli (ST36), and Shangjuxu (ST37), emphasize the application of special acupoints, meridian points and nerve segments, and the two-way regulatory effect found in this study is often used as the basis of acupoint selection and acupoint prescription for acupuncture treatment of FGIDs.

Revealing characteristics and rules of acupoint sensitization phenomena: based on knee osteoarthritis / 中国针灸

OBJECTIVE@#To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion.@*METHODS@#In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint.@*RESULTS@#Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients.@*CONCLUSION@#It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.

Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway.

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1ß, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1ß, and TNF-α; and lowered levels of colonic inflammation.

Research progress on chemical constituents and pharmacological activities of seabuckthorn and prediction of its Q-markers / 中国中药杂志

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.

Effectiveness and Safety of Acupoint Application of Guan Xin Su He Pill () for Patients with Chronic Stable Angina Pectoris: A Multi-Center, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To assess the clinical effectiveness of acupoint application (AP) of Guan Xin Su He Pill (, GXSHP) for patients with chronic stable angina pectoris (CSAP).@*METHODS@#This study was carried out in 3 local hospitals in Chengdu, China. After baseline evaluation, eligible patients were randomly assigned to the placebo application for acupoints (PAA) group or the herbal application for acupoints (HAA) group. Patients in the HAA group underwent AP with herbal powder, which was mainly GXSHP, and patients in the PAA group underwent AP with sham drugs. For each treatment session, unilateral acupoints including Neiguan (PC 6), Danzhong (RN 17), Xinshu (BL 15) and Jueyinshu (BL 14), were stimulated for both groups. AP was performed 3 times a week with a 2-day interval for 4 weeks. The primary outcome was the frequency of angina pectoris attacks per week, while the secondary outcomes included angina pain intensity measured by the Visual Analogue Scale (VAS), dose of rescue oral drugs (nitroglycerin), scores on the Seattle Angina Questionnaire (SAQ), Self-Rating Anxiety Scale scores (SAS) and Self-Rating Depression Scale scores (SDS). Clinical outcomes were measured at week 0, 4 and 8. The safety of AP of GXSHP treatment for CSAP were assessed.@*RESULTS@#A total of 121 patients were enrolled. Baseline characteristics were comparable across the 2 groups. After treatment, the angina attack numbers in the HAA group were significantly reduced from 11.00 to 4.81 (P<0.05). While, for PAA group, the angina frequency was not significantly improved (baseline 10.55; post-treatment 11.05). The HAA group had significantly fewer angina attacks than the PAA group (P<0.05). Pain intensity measured by VAS in HAA group was significantly reduced from 4.06 to 3.02 (P<0.05). While, for PAA group, the VAS was significantly increased (baseline 3.62; post-treatment 3.96; P<0.05). Clinical outcomes showed better improvement after treatment in the HAA group than in the PAA group in terms of oral administration of rescue drugs, SAS, SDS and SAQ scores (P<0.05). The adverse events were also reported.@*CONCLUSION@#AP of GXSHP is a safe and effective treatment for CSAP patients (Registration No. NCT02029118).

TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches / 中国天然药物

Traditional Chinese medicine (TCM) is a precious treasure of the Chinese nation and has unique advantages in the prevention and treatment of diseases. The holistic view of TCM coincides with the new generation of medical research paradigm characterized by network and system. TCM gave birth to a new method featuring holistic and systematic "network target", a core theory and method of network pharmacology. TCM is also an important research object of network pharmacology. TCM network pharmacology, which aims to understand the network-based biological basis of complex diseases, TCM syndromes and herb treatments, plays a critical role in the origin and development process of network pharmacology. This review introduces new progresses of TCM network pharmacology in recent years, including predicting herb targets, understanding biological foundation of diseases and syndromes, network regulation mechanisms of herbal formulae, and identifying disease and syndrome biomarkers based on biological network. These studies show a trend of combining computational, experimental and clinical approaches, which is a promising direction of TCM network pharmacology research in the future. Considering that TCM network pharmacology is still a young research field, it is necessary to further standardize the research process and evaluation indicators to promote its healthy development.

Effectiveness of mindfulness training on emotional regulation and resilience of college students / 中华行为医学与脑科学杂志

Objective:To investigate the effectiveness of mindfulness training on the emotional regulation and resilience of college students.Methods:Eighty one college students were recruited and randomly divided into mindfulness training group and control group, of which 74 completed the study (36 in mindfulness training group and 38 in control group). Participants in mindfulness training group received an 8-week mindfulness training, while participants in control group received no intervention. Participants were assessed with the Five Facet Mindfulness Questionnaire (FFMQ, measuring mindfulness level), Profile of Mood State (POMS, measuring emotion) and the Resilience Scale for Chinese Adolescent(RSCA, measuring resilience) before and after intervention (4 and 8 weeks).Results:Before and after the intervention, the interaction effects of total score of five factors mindfulness, scores of observing, actaware, non-judging, total score of resilience, scores of goal planning, help-seeking and the fatigue score were significant(all P<0.05). There were significant differences in mindfulness level, mood state and resilience scores in mindfulness training group before and after intervention(all P<0.05). There were significant differences of scores of FFMQ , POMS and RSCA post-training compared with baseline( P<0.05). The total score of FFMQ was improved significantly after 4 weeks of intervention ((114.92±11.70) vs(110.36±11.24), P<0.05), while the scores of observing((26.19±5.21) vs(24.00±5.34)), describing((23.36±4.82) vs(21.19±4.76)), non-judging((23.75±4.20) vs(22.06±4.99)) and non-reacting((19.72±3.16) vs(18.58±3.61)) were improved significantly after 8 weeks of intervention. There were significant differences of the scores of fatigue, depression-dejection, panic, vigor-activity and total mood disturbance before and after the intervention in mindfulness training group (all P<0.05). The scores of fatigue((12.31±4.08) vs(13.39±5.12)), panic((12.08±3.57) vs(13.67±4.35)) and total mood disturbance((132.94±17.71) vs(145.75±22.68)) were reduced significantly after 8 weeks of intervention (all P<0.05), while the scores of vigor-activity were improved significantly after 8 weeks of intervention ((18.31±4.61) vs (15.39±4.99), P<0.01). The participants in mindfulness training group got significantly higher total score, scores of goal planning, help-seeking, and affect control of RSCA after intervention compared with baseline (all P<0.05). Conclusion:Mindfulness training can enhance the mindfulness level and resilience of college students, decrease negative affect such as fatigue, depression, panic, and increase positive affect such as activity.

Clinical observation on distribution characteristics and rules of pain sensitivity points on body surface in patients with knee osteoarthritis / 中国针灸

OBJECTIVE@#To observe the distribution characteristics and rules of pain sensitivity points on body surface in patients with knee osteoarthritis (KOA).@*METHODS@#A total of 916 patients with KOA were selected in this study, the pain sensitivity points of local site of knee joint were probed by thumb palpation. Tape was used to measure the distance between the pain sensitivity points and the most nearby acupoints. The Wagner tenderness measuring instrument was used to measure the tenderness threshold of pain sensitivity points.@*RESULTS@#A total of 3618 pain sensitivity points were probed, among them, 3338 pain sensitivity points were sensitized. The minimum sensitization degree was 1.00, the maximum sensitization degree was 3.39, while the average sensitization degree was (2.16±0.60). Pain sensitivity points were distributed 0.37-1.73 @*CONCLUSION@#The pain sensitivity points of patients with KOA may be the expansion effect of acupoint areas in the disease states, pain sensitivity points are more likely to appear on the medial side of knee joint.

Xiaoyaosan improves depressive-like behavior in rats with chronic immobilization stress through modulation of the gut microbiota.

Depression has become the leading cause of disability worldwide and a growing public health problem in China. In addition, intestinal flora may be associated with depression. This study investigated the effect of the decoction Xiaoyaosan (XYS) against depressive behavior through the regulation of intestinal flora. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (i.e., control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to produce the stress depression model. Rats in the XYS and fluoxetine groups received intragastric administration of XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. Stool specimens were sequenced using the 16S rDNA high-throughput method to detect the structure and changes in intestinal flora. There was no difference observed in alpha diversity among the groups. At the phylum level, XYS regulated the abundance of Bacteroidetes, Proteobacteria, Firmicutes, Chloroflexi, and Planctomycetes. At the genus level, XYS reduced the abundance of the Prevotellaceae_Ga6A1_group, Prevotellaceae_UCG-001, and Desulfovibrio. On the contrary, it increased the abundance of the Ruminococcaceae family to improve depression-like behavior. The mechanism involved in this process may be related to short-chain fatty acids, lipopolysaccharides, and intestinal inflammation.

Effects of electroacupuncture on insulin resistance in patients with knee arthroplasty / 中国针灸

OBJECTIVE@#To explore the effect of electroacupuncture on the improvement of insulin resistance after knee joint replacement based on the combined spinal and epidural anesthesia and postoperative epidural analgesia.@*METHODS@#Eighty patients with insulin resistance but normal blood glucose were randomly divided into a control group and an observation group, 40 cases in each group.Both groups of patients underwent combined spinal and epidural anesthesia and postoperative epidural analgesia for knee arthroplasty. On the basis of the treatment,electroacupuncture (EA) was applied during the operation and within 1 month after the operation in the observation group, and EA was used at Hegu (LI 4), Qihai (CV 6), Zhongwan (CV 12), Pishu (BL 20), Shenshu (BL 23), etc. once every other day. The control group was not treated with electroacupuncture. Fasting blood glucose and fasting insulin were recorded 30 min before surgery (T), immediately (T), 1 d (T), 3 d (T), 7 d (T) and 1 month (T) after surgery, and the insulin resistance (IR) index was calculated.@*RESULTS@#Compared with those at T time point, the IR index of the control group at T, T, T and T time points and the observation group at T, T, T time points were lower (all <0.05). Compared with the control group at the same time point, the IR index of the T and T time points in the observation group was significantly lower (both <0.05), and it was lower than the insulin resistance standard.@*CONCLUSION@#Combined spinal and epidural anesthesia and postoperative epidural analgesia can improve short-term insulin resistance. Combined with EA, the improvement of insulin resistance is more obviously and longer.

Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial / 中西医结合学报

BACKGROUND@#Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of "stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of "harmonizing stomach to tranquilize mind" acupuncture for insomnia and its influence on the intestinal microbiome.@*METHODS/DESIGN@#This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups (1:1 allocation ratio). The intervention group will use "harmonizing stomach to tranquilize mind" acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment.@*DISCUSSION@#The results of this trial are expected to confirm that "harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome.@*TRIAL REGISTRATION@#Chinese Clinical Trials Registry: ChiCTR1800017092.

Identification and analysis on medicinal plants of Labiatae from Emei Mountain Area Using ITS2 and matK sequences / 中草药

Objective: To evaluate the efficiency of ITS2 and matK DNA barcode for the identification the Labiatae medicinal plants in Emei Mountain. Methods: A total of 23 samples of Labiatae medicinal plants were harvested in Emei Mountain. The DNA was extracted and used for PCR to obtain the ITS2 sequences. Meanwhile, 54 ITS2 and 51 matK sequences of the medicinal plants in Labiatae were downloaded from Genbank. The interspecies and intraspecific genetic distance and sequence variation sites of all sequences were determined by MEGA 5.0 software. The Neighbor Joining (NJ) phylogenetic tree was constructed, and barcoding gap analysis was then performed. Results: The length of various ITS2 sequence was distributed from 190 to 237 bp, with GC content of 53%-73%. Moreover, significant barcoding gap was observed when comparing the distances, the recognition rate for plants of the Labiatae family was 94%.The barcoding gap of the matK sequence was not significant, there was obvious overlap, and the recognition rate for the Labiatae family was 96%. Conclusion: ITS2 has a better ability to identify Lamiaceae plants at the species level, but the matK sequence has a higher recognition rate for Lamiaceae plants. Therefore, the employment of ITS2 as core with matK as supplement was able to identify Lamiaceae plants quickly and accurately, and understand the genetic relationship between species accurately. This provides an important theoretical basis for the effective protection and rational development of the medicinal plant resources of the Labiatae plants in Emei Mountain.

Two new iridoid glycosides from the leaves of Callicarpa nudiflora.

Two new iridoid glycosides, callicoside C (1) and callicoside D (2), together with three known compounds (3-5), were isolated from the leaves of Callicarpa nudiflora. Their structures were established by 1D and 2D NMR spectroscopy and mass spectrometry. In an in vitro bioassay, compound 1 showed pronounced hepatoprotective activity against d-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.

Study of acupuncture for low back pain in recent 20 years: a bibliometric analysis via CiteSpace.

BACKGROUND: Acupuncture has been applied to relieve low back pain (LBP) in many countries. However, a bibliometric analysis of the global use of acupuncture for LBP is rare. OBJECTIVE: The aim of this study was to demonstrate the state of the art and trends concerning the global use of acupuncture for LBP in recent 20 years. METHODS: Literature relating to acupuncture for LBP from 1997 to 2016 was retrieved from Web of Science. CiteSpace was used to analyze country/institution, cited journals, authors/cited authors, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers. RESULTS: A total of 958 references were obtained, and the total number of publications continually increased over the investigated period. Journal articles (662) were the most frequently occurring document type. The most productive country and institution in this field was the USA (342) and Harvard University (47), respectively. The J Altern Complem Med (69) was the most productive journal, and Pain (636) was the most cocited journal, which reflected the nature of the research. The Haake's (2007) article (cocitation counts: 130) and the Cherkin's (2001) article (centrality: 0.59) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. Cherkin was the most influential author, with the highest number of publications of 25 and a cocitation number of 226. The four hot topics in acupuncture for LBP were research method, evaluation, economy, and comprehensive therapy. The three frontier topics were intervention, test reliability, and prevalence. CONCLUSION: This study provides an insight into acupuncture for LBP and valuable information for acupuncture researchers to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers.

Hepatoprotective iridoid glucosides from Callicarpa nudiflora.

Two new iridoid glucosides, callicoside A (1) and callicoside B (2), were isolated from the leaves of Callicarpa nudiflora. Their structures were elucidated by means of spectroscopic methods and chemical evidences. In an in vitro bioassay, compound 1 showed pronounced hepatoprotective activity against D-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.

Study on health-seeking behavior and influencing factors among Chinese hepatitis B surface antigen positive adults / 中华流行病学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of health-seeking behaviors and related influencing factors of the community-based hepatitis B surface antigen (HBsAg) positive adults, in China.</p><p><b>METHODS</b>Based on the cohort formed by the HBsAg positive patients, in the national sero-survey project in 2006, we conducted a follow-up programs in 2010 and 2014. In the latest follow-up project, we carried out a cross-sectional study to collect information on health-seeking behaviors of the patients. Questionnaires would include information on clinic visits, diagnosis, regular physical examination and treatments,etc. We used the SPSS 18.0 software for data analysis.</p><p><b>RESULTS</b>Totally, 2 478 HBsAg positive adults (≥18 years old) were followed through, with 34.4% (853/2 478) of them had visited the doctors and diagnosed after they were informed the status of HBsAg positivity, in the 2006-sero-survey program. Among patients who ever visiting the clinic, 51.2% (372/727) of them underwent at least medical examination once a year, with 31.5% (229/727) of them received treatment. Furthermore, 34.5% (79/229) of the treated patients adopted the traditional Chinese medicine or medicine for ' liver protection'. 56.8% (130/229) of the treated patients received antiviral drugs. Data from the binary logistic regression showed that the major influencing factors on clinic visits would include: age, level of education received and residencial areas (rural/urban).</p><p><b>CONCLUSIONS</b>Consciousness on health was low in those community-based HBsAg positive people. Standerdized management and clinical treatment programs should be set up accordingly.</p>

[Chemical Constituents from Camellia oleifera Stem].

OBJECTIVE: To study the chemical constituents of stem of Camellia oleifera. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-ß-D-glucopyranosyl- (1 --> 2) -ß-D-xylopyransoyl-(1 --> 3) -[ß-D-glucopyranosyl- (1 --> 2)] -ß-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol (6) and oleanolic acid (7). CONCLUSION: Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time.

Two new triterpenoids from Callicarpa kwangtungensis.

Two new triterpenoids, 2α,3ß,16α,19α,23-pentahydroxyolean-12-en-28-oic acid (1) and 2α,3α,11α,21α,23-pentahydroxyurs-12-en-28-oic acid (2), were isolated from the aerial parts of Callicarpa kwangtungensis. Their structures were elucidated by 1D and 2D analyses, as well as MS and IR spectra.

Comments on "Acupuncture for chronic knee pain: a randomized clinical trial" from Journal of the American Medical Association / 中国针灸

The development of TCM acupuncture represents a internationalized and modern trend. A recent study with the title of "Acupuncture for chronic knee pain: a randomized clinical trial" published in Journal of the American Medical Association on October 1st, 2014, which raised doubts on acupuncture efficacy as well as traditional manipulation and acupoint theory, makes some negative impact and challenges on the development of acupuncture. From the view of future development of acupuncture, the potential influence of this research on acupuncture development is proposed, and by combining acupuncture theory, some discussions and doubts on the research design and outcome explanations are made. Additionally, enlightenments of this research on further clinical research are summarized.

Inhibitory effects of mesenchymal stem cells on antigen-specific T cells and antigen presenting cells in experimental autoimmune uveitis / 中华实验眼科杂志

Background Our previous studies found that mesenchymal stem cells (MSCs) can ameliorate experimental autoimmune uveitis (EAU) and reduce tissue impairment.Its mechanism is still pending.Objective This study was performed to investigate the effects of MSCs on T cell subsets and antigen presenting cells (APCs) in EAU rats.Methods MSCs were isolated from bone marrow of six male Wistar rats and cultured by plastic adherence method.Twelve female Lewis rats were assigned randomly into MSCs group and PBS group.EAU rat model was induced by immunization with 200 μl emulsion containing 30 μg interphotoreceptor retinoid-binding protein (IRBP) 1177-1191 polypeptide fragment R16 and complete Freund adjuvant (CFA).The eye manifestations of the rats were observed and scored under the slit lamp microscope after modeling.The R16-immunized rats were treated intravenously with 5×106/ml MSCs for 3 consecutive days from day 9 to 11 after modeling in the MSCs group,and the equivalent volume of PBS was used with the same way in the PBS group.Fifteen days after modeling,the spleens and draining lymph nodes were collected to evaluate the proportion of interferon-γ (IFN-γ) positive CD4+ T cells,interleukin-17 (IL-17)positive CD4+ T cells and forkhead helix transcription factor p3 (Foxp3) positive CD4+ T cells by flow cytometry.The T cells and APCs from the different groups were cocultured and divided into PBS cocultured group,MSCs cocultured group, PBS-MSCs cross-cultured group and MSCs-PBS cross-cultured group under the stimulation of R16 at the concentration of 0.3,1.0 or 10.0 μg/ml, and the proliferation indexes of the T cells in different groups were assayed by 5-bromodeoxyuridine (BrdU) Elisa kit.The use of experimental animals complied with the regulations on the management of experimental animals promulgated by the national science and technology commission.Results The ocular surface inflammatory scores of 11,12,13 and 14 days after modeling in the MSCs group were significantly lower than that in the PBS group (t=3.825,5.100,4.250,3.400, all at P＜0.05).Compared with the PBS group, the proportions of IFN-γ positive CD4+ T cells in spleen and draining lymph notes were considerably decreased in the MSCs group (t =5.651,4.376, both at P＜0.05) , so were the IL-17+ CD4+ T cells (t =3.300,4.925, both at P＜0.05).However,the proportions of Foxp3 + CD4+ T cells in spleen and draining lymph notes were statistically raised in the MSCs group compared with the PBS group (t =-5.172,-2.825,both at P＜0.05).The proliferation index of T cells increased with the rise of R16 dose in the PBS cocultured group, and the proliferation indexes were all declined in the MSCs cocultured group compared with the PBS cocultured group under the stimulation of 0.3,1.0 and 10.0 μg/ml of R16 (P =0.027,0.000,0.000).In addition, significant reduces of proliferation indexes of T cells were seen in the PBS-MSCs cross-cultured group and MSCs-PBS cross-cultured group in comparison with the PBS cocultured group when stimulated by 1.0 μg/ml and 10.0 μg/ml R16 (1.0 μg/ml R16 : P =0.001,0.000;10.0 μg/ml R16:P=0.000,0.000).Conclusions MSCs can ameliorate EAU by inhibiting the functions of antigen-specific T cells and APCs and up-regulating T regulatory cells in EAU rats.