The effect of massage on patients with chronic fatigue syndrome: A systematic review and meta-analysis.

BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term and complex chronic disease that seriously affects the physical and mental health and quality of life of patients. Massage, as one of the methods in traditional Chinese medicine, can treat both symptoms and root causes and is widely used to treat CFS. The main purpose is to systematically evaluate the impact of massage therapy on the efficacy and safety of CFS patients, providing a reference for clinical practice. METHODS: By searching for literature published in PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, VIP Database, and China National Knowledge Infrastructure Database until November 2023, randomized controlled trial studies were selected according to the established inclusion and exclusion criteria. The Cochrane system evaluation manual was used to evaluate the quality of the included studies, and RevMan5.4 software was used for meta-analysis. RESULTS: 32 randomized controlled trials were included, with a total of 2594 CFS patients. Meta-analysis showed that the total score of the fatigue scale (FS-14) in the treatment group, MD = -1.59, 95% CI (-1.84, -1.34), P < .00001; Physical fatigue score, MD = -1.30, 95% CI (-1.60, -1.00), P < .00001; Mental fatigue score, MD = -0.84, 95% CI (-0.99, -0.72), P < .0001]; Effective rate [RR = 1.23, 95% CI (1.19,1.28), P < .00001]; all indicators were superior to the control group, Only one study reported adverse reactions, including local swelling, skin bruising, and nausea. CONCLUSION: Our research findings suggest that massage therapy has a significant therapeutic effect on CFS, avoiding adverse reactions and improving fatigue symptoms. Therefore, massage therapy for chronic fatigue syndrome should be further promoted and applied.

GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice.

Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.

[Retracted] A disintegrin and metallproteinase 15 knockout decreases migration of fibroblast­like synoviocytes and inflammation in rheumatoid arthritis.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting assay data shown in Figs. 1B and 5A and the histological data shown in Fig. 6C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 11: 4389­4396, 2015; DOI: 10.3892/mmr.2015.3302].

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice.

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

Dopamine D2 receptor within the intermediate region of the lateral septum modulate social hierarchy in male mice.

The dopamine (DA) system has long been involved in social hierarchies; however, the specific mechanisms have not been elucidated. The lateral septum (LS) is a limbic brain structure that regulates various emotional, motivational, and social behaviors. DA receptors are abundantly expressed in the LS, modulating its functions. In this study, we evaluated the functions of DA receptors within different subregions of the LS in social dominance using a confrontation tube test in male mice. The results showed that mice living in social groups formed linear dominance hierarchies after a few days of cohousing, and the subordinates showed increased anxiety. Fos expressions was elevated in the entire LS after a confrontation tube test in the subordinates. However, DA neurons were more activated in the dominates within the ventral tegmental area and the dorsal raphe nucleus. Quantitative real-time polymerase chain reaction results showed that D2 receptor (D2R) within the intermediate region of the LS (LSi) were elevated in the subordinate. In the following pharmacological studies, we found simultaneous D2R activation in the dominants and D2R inhibition in the subordinates switched the original dominant-subordinate relationship. The aforementioned results suggested that D2R within the LSi plays an important role in social dominance in male mice. These findings improve our understanding of the neural mechanisms underlying the social hierarchy, which is closely related to our social life and happiness.

5-HT1A receptor in the central amygdala and 5-HT2A receptor in the basolateral amygdala are involved in social hierarchy in male mice.

Most social animals self-organize into dominance hierarchies that strongly influence their behavior and health. The serotonin (5-HT) system is believed to play an important role in the formation of social hierarchy. 5-HT receptors are abundantly expressed in the amygdala, which is considered as the central node for the perception and learning of social hierarchy. In this study, we assessed the functions of various 5-HT receptor subtypes related to social rank determination in different subregions of the amygdala using the confrontation tube test in mice. We revealed that most adult C57BL/6 J male mice exhibited a linear social rank after a few days of cohousing. The tube test ranks were slightly related to anxiety-like behavioral performance. After the tube test, the amygdala and 5-HT neurons in the dorsal raphe nucleus were activated in lower-rank individuals. Quantitative real-time polymerase chain reaction analysis revealed that despite the high expression of 5-HT1A receptor mRNA in the central amygdala (CeA), 5-HT2A receptor mRNA expression was downregulated in the basolateral amygdala (BLA) in higher-rank individuals. The dominant-subordinate relationship between mouse pairs could be switched via pharmacological modulation of these receptors in CeA and BLA, suggesting that these expression changes are essential for establishing social ranks. Our findings provide novel insights into the divergent functions of 5-HT receptors in the amygdala related to social hierarchy, which is closely related to our health and welfare.

Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress.

INTRODUCTION: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. METHODS AND RESULTS: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. CONCLUSIONS: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.

Acupuncture combined with traditional Chinese medicine for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: With the aging of society, the incidence of knee osteoarthritis (KOA) is increasing year by year, which seriously affects the quality of life. Acupuncture therapy has been widely used in the treatment of osteoarthritis, but there is no complete systematic review on acupuncture combined with traditional Chinese medicine. Therefore, this study aims to clarify the efficacy and safety of acupuncture combined with traditional Chinese medicine in the treatment of KOA through systematic review and meta-analysis. METHODS: A structured and systematic literature search will be conducted in the following databases up to March, 20, 2022: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/). We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This meta-analysis further established the efficacy of acupuncture combined with traditional Chinese medicine in the treatment of KOA. CONCLUSION: This meta-analysis aims to investigate the efficacy of acupuncture combined with traditional Chinese medicine on patients with KOA and provide reliable evidence. To provide more options for clinicians and patients in the treatment of KOA.

Tuina for shoulder pain after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke shoulder pain is a relatively common complication in stroke patients, with an incidence of 16% to 84% and poor outcomes with anti-inflammatory or sedative medications. This study will evaluate the results of a randomized controlled trial to determine the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. METHODS: The Chinese and English search strategies were used to search China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, PubMed, Wanfang Database, and Web of Science were used to search seven databases. All eligible studies published on or before September 15, 2022, will be selected. To improve the validity of this study, only clinical randomized controlled trials related to the use of Tuina for post-stroke shoulder pain will be included. The screening will be performed by 2 independent reviewers and data synthesis, bias analysis, subgroup analysis, and meta-analysis will be performed using RevMan (V.5.4) software. RESULTS: The study will provide a high-quality evaluation of the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. CONCLUSION: This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for treating patients with post-stroke shoulder pain.PROSPERO registration number: CRD42022360401.

Acupuncture-related techniques for prevention of type 2 diabetes mellitus in people with pre-diabetes: Protocol for a systematic review and meta-analysis.

BACKGROUND: In modern society, the incidence of diabetes is increasing year by year. Most individuals pass through a phase of prediabetes before developing full blown diabetes. Acupuncture-related has been widely used in the treatment of diabetes, but there is no systematic review of acupuncture-related on the control of blood glucose in prediabetes. Therefore, this study aims to conduct a meta-analysis of the clinical efficacy of acupuncutre-related therapy in preventing the development of diabetes in patients with prediabetes. METHODS: We will search Web of Science, The Cochrane Library, PubMed, Embase, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wan-Fang Database, Chinese Scientific Journal Database (VIP Database) from their respective inception dates to September 1, 2022 to identify potentially eligible studies. We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This meta-analysis further elucidates the protective effects of acupuncture-related techniques on patients with prediabetes. CONCLUSION: The purpose of this meta-analysis was to investigate the effect of acupuncture- related techniques on blood glucose in patients with prediabetes, and to provide more methods for clinical prevention of conversion from prediabetes to diabetes.

A systematic review of Tuina for cervical hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervical hypertension is a secondary form of hypertension with a high incidence rate. As the main etiology of cervical hypertension is related to cervical spondylosis, commonly used antihypertensive drugs have poor efficacy in the treatment of cervical spondylosis, and improving the symptoms of cervical spondylosis can effectively reduce blood pressure. Massage can effectively improve the symptoms of patients with cervical hypertension, but there has been no systematic review of massage treatment for cervical hypertension. This study aimed to evaluate the efficacy and safety of massage in patients with cervical hypertension. METHODS: Before February 10, 2022, a systematic literature search was conducted using the following databases: Embase, SinoMed (previously called the Chinese Biomedical Database), China Science and Technology Journal Database for Chinese Technical Periodicals, Chinese National Knowledge Infrastructure, and Wanfang Data. Review Manager software (version 5.3) will be used for statistical analysis. Quality and risk assessments of the included studies were performed, and the outcome indicators of the trials were observed. RESULTS: This meta-analysis further confirmed the beneficial effects of massage in patients with cervical hypertension. CONCLUSION: This study investigated the efficacy and safety of massage therapy in patients with cervical hypertension, providing clinicians and patients with additional options for the treatment of this disease.

[Clinical observation on cluster acupuncture at scalp points combined with exercise therapy in treatment of limb spasm after stroke].

OBJECTIVE: To observe the clinical effect of cluster acupuncture at scalp points in treating limb spasm after stroke on the basis of conventional exercise therapy. METHODS: A total of 72 patients with limb spasm after stroke were randomly divided into an observation group (36 cases, 5 cases dropped off) and a control group (36 cases, 6 cases dropped off). The control group was treated with exercise therapy. In the observation group, on the basis of the control group, penetrating technique of acupuncture was exerted at Qianding (GV 21) to Baihui (GV 20), Xinhui (GV 22) to Qianding (GV 21), etc. once a day, 5 days a week for 4 weeks. Before and after treatment, the changes of the modified Ashworth scale (MAS), simplified Fugl-Meyer motor assessment (FMA), and modified Barthel index (MBI) scores of the two groups were compared. RESULTS: After treatment, the MAS scores of upper and lower limbs in the two groups were lower than before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, the scores of FMA and BMI in the two groups were higher than before treatment (P<0.05), and the score of MBI in the observation group was higher than the control group (P<0.05). CONCLUSION: On the basis of conventional exercise therapy, cluster acupuncture at scalp points can reduce the spasm, improve motor function and activities of daily living in patients with limb spasm after stroke.

mGlu2/3 receptors within the ventral part of the lateral septal nuclei modulate stress resilience and vulnerability in mice.

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs' agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.

Efficacy and safety of external therapy of TCM for diabetic peripheral vascular disease: A protocol for systematic review and meta-analysis.

BACKGROUND: In modern society, the incidence of diabetes is increasing yearly, and poor glycemic control can accelerate the progression and severity of diabetic peripheral vascular disease. External treatment with traditional Chinese medicine (TCM) has been widely used in the treatment of diabetes, but there is no systematic review on the external treatment of TCM for diabetic peripheral vascular disease; therefore, this study aimed to conduct a meta-analysis on the clinical efficacy and safety of external treatment of TCM in the treatment of diabetic peripheral vascular diseases. METHODS: We searched The Cochrane Library, PubMed, Web of Science, EMBASE, China Science and Technology Journal, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and other sources from their respective inception dates to October 20, 2022, to identify potentially eligible studies. We will use Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed their outcome measures. RESULTS: Changes in the bilateral femoral artery, popliteal artery, dorsal artery diameter, blood flow, ankle/brachial index, and dorsal foot temperature: An overall reduction in symptoms (a reduction in diabetes-related symptoms that occur only during the intervention or as a result of the intervention, including peripheral vascular disease). CONCLUSION: The objective of this meta-analysis was to investigate the influence of external treatment of traditional Chinese medicine on diabetic peripheral vascular disease and to provide more methods for the clinical prevention and treatment of diabetic peripheral vascular disease.

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation.

Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

Tuina for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Tuina therapy has been widely used in the treatment of DPN, but there is no systematic review on the treatment of DPN. Therefore, this study aimed to conduct a meta-analysis of Tuina in the treatment of DPN to clarify its efficacy. METHODS: The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and May 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to Tuina for diabetic peripheral neuropathy were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of Tuina for treating diabetic peripheral neuropathy. CONCLUSION: This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for patients with diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. REGISTRATION NUMBER: INPLASY202150027.

Tuina for spasticity of poststroke: protocol of a systematic review and meta-analysis.

INTRODUCTION: Spasticity is a common complication of poststroke, tuina is a widely used rehabilitation treatment, although there is a lack of supportive evidence on efficacy and safety for patients with poststroke spasticity. The aim of this systematic review is to assess and synthesis evidence of efficacy and safety of tuina for spasticity of poststroke. METHODS AND ANALYSIS: A comprehensive electronic search of EMBASE, MEDLINE, Cochrane Library, Web of Science, Wiley, Springer, PEDro, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database (VIP), Wanfang Database (Wanfang), Japanese medical database (CiNii), Korean Robotics Institute Summer Scholars and Thailand Thai-Journal Citation Index Centre will be conducted to search literatures of randomised controlled trials of tuina for spasticity of poststroke survivors range from the establishment to 1 January 2020.There is no time of publication limitations. The primary outcome will be measured with the Modified Ashworth Scale, and the second outcome will include Fugl-Meyer Assessment Scale, surface electromyogram RMS value, the Modified Barthel Index, Stroke Specific Quality of Life Scale, quality of life 36-Item Short-Form Health Survey and Visual Analogue Scale. Cochrane Handbook for Systematic Reviews of Interventions will be used to assess the risk of bias, and GRADE will be used to access the confidence in cumulative evidence. The protocol will be conducted according to approach and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015. ETHICS AND DISSEMINATION: Ethical approval will not be required, for no primary data of individual patients were collected. We will publish the findings in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020163384.

The effects of cytarabine combined with ginsenoside compound K synergistically induce DNA damage in acute myeloid leukemia cells.

AML is a kind of hematological malignant tumor that urgently requires different treatment options in order to increase the cure rate and survival rate. Cytarabine (ara-C) is currently the main drug used to treat AML patients and is usually combined with different chemotherapeutic agents. However, due to resistance to ara-C, a new combination is needed to reduce ara-C resistance and improve treatment outcome. As is known to all, ginseng is a traditional Chinese herb; compound K is the principal metabolic product of ginsenoside which also has anti-cancer activity in some cancer cells, while the mechanism is unclear. In our previous study, we found that compound K inhibited AML cell viability and induced apoptosis, and compound K combined with ara-C synergistically induced AML cell proliferation arrest. Thus, we sought to investigate the reason for this by focusing on the mitochondrial dysfunction and DNA damage. In this paper, our results provide a foundation for the clinical evaluation of concomitant administration of compound K and ara-C in order to reduce the resistance to ara-C and improve AML treatment.

Platelet Protease Activated Receptor 1 Is Involved in the Hemostatic Effect of 20(S)-Protopanaxadiol by Regulating Calcium Signaling.

Panax notoginseng (Burk.) F.H. Chen has long been used to stop bleeding for hundreds of years in China. At present, only dencichine, notoginsenoside Ft1, and 20(S)-protopanaxadiol (PPD) showed hemostatic effect. However, the molecular mechanism of PPD on the platelet aggragetion needs to be further investigated. The study aims to evaluate the hemostatic effect of PPD and reveal its interacting targets using a series of experiments. In this study, the bleeding time was measured in mouse tail amputation and liver scratch models to evaluate hemostatic effect of PPD. The routine blood and plasma coagulation parameters in NS, HC, and PPD (2, 4, and 8 mg/kg) groups were measured using a blood analyzer. Platelet aggregation rate and ATP release were analyzed by a platelet aggregometer. Subsequently, the degranulation marker CD62P and PAC-1, and the concentrations of cytosolic Ca2+ ([Ca2+]i), cAMP, cGMP, and PAC-1 expressions were also assessed. We found that PPD shorted the bleeding time on the mouse tail amputation and liver scratch models and mainly increased blood platelet count in the rats after subcutaneous injection for 4 h. Meanwhile, PPD decreased APTT, increased FIB content, and directly induced platelet aggregation in vitro. In the absence of Ca2+, PPD induced the increase of [Ca2+]i and slightly increased the levels of CD62P and PAC-1. After the addition of 1 mM Ca2+, PPD treatment markedly promoted platelet activation by promoting ATP level, releasing CD62P and increasing PAC-1 binding in washed platelets. Excitingly, PPD-induced changes including platelet aggregation, decreased cAMP content, and the increases of CD62P and PAC-1 were significantly reversed by protease-activated receptor 1 (PAR-1) antagonist, vorapaxar, which showed similar function as thrombin. In addition, molecular docking analysis and ELISA assay demonstrated that PPD had a promising docking score with -6.6 kcal/mol and increased PAR-1 expression in human platelets, which indicated that PAR-1 is involved in PPD-induced platelet aggregation by regulating calcium signaling. Collectively, our study could provide the new insights of PPD as an essential hemostatic ingredient in Panax notoginseng for the treatment of hemorrhagic disease.