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BACKGROUND: Lumbar disc herniation was regarded as an age-related degenerative disease. Nevertheless, emerging reports highlight a discernible shift, illustrating the prevalence of these conditions among younger individuals. METHODS: This study introduces a novel deep learning methodology tailored for spinal canal segmentation and disease diagnosis, emphasizing image processing techniques that delve into essential image attributes such as gray levels, texture, and statistical structures to refine segmentation accuracy. RESULTS: Analysis reveals a progressive increase in the size of vertebrae and intervertebral discs from the cervical to lumbar regions. Vertebrae, bearing weight and safeguarding the spinal cord and nerves, are interconnected by intervertebral discs, resilient structures that counteract spinal pressure. Experimental findings demonstrate a lack of pronounced anteroposterior bending during flexion and extension, maintaining displacement and rotation angles consistently approximating zero. This consistency maintains uniform anterior and posterior vertebrae heights, coupled with parallel intervertebral disc heights, aligning with theoretical expectations. CONCLUSIONS: Accuracy assessment employs 2 methods: IoU and Dice, and the average accuracy of IoU is 88% and that of Dice is 96.4%. The proposed deep learning-based system showcases promising results in spinal canal segmentation, laying a foundation for precise stenosis diagnosis in computed tomography images. This contributes significantly to advancements in spinal pathology understanding and treatment.
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Aprendizaje Profundo , Canal Medular , Estenosis Espinal , Tomografía Computarizada por Rayos X , Humanos , Estenosis Espinal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Canal Medular/diagnóstico por imagen , Masculino , Vértebras Lumbares/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Procesamiento de Imagen Asistido por Computador/métodos , Adulto , Desplazamiento del Disco Intervertebral/diagnóstico por imagenRESUMEN
OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.
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Terapia por Acupuntura , Artritis Experimental , Quimiocina CXCL1 , Receptores de Interleucina-8B , Corteza Somatosensorial , Animales , Humanos , Masculino , Ratones , Ratas , Puntos de Acupuntura , Artritis Experimental/terapia , Artritis Experimental/metabolismo , Artritis Experimental/genética , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Inflamación/terapia , Inflamación/metabolismo , Inflamación/genética , Ratones Endogámicos BALB C , Dolor/metabolismo , Dolor/genética , Manejo del Dolor , Ratas Wistar , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Transducción de Señal , Corteza Somatosensorial/metabolismoRESUMEN
Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.
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Depression is a common mental disorder caused by the interaction of social, psychological, and biological factors. Treatments include psychotherapy, pharmacotherapy, and other therapies, but they have limitations. Particularly, the COVID-19 pandemic may have a negative impact on depressed people. Thus, developing more potential treatments for depression has currently been an urgent challenge. A growing number of studies have found that acupressure is effective in relieving the symptoms of depression. Thus, this study aimed to evaluate the efficacy and safety of acupressure in people with depression. English (PubMed, CENTRAL, EMBASE, APA PsycINFO, and CINAHL) and Chinese databases (CBM, CNKI, Wanfang, and VIP), ClinicalTrials.gov and Chinese Clinical Trial Registry were searched for randomized controlled trials (RCTs) on patients diagnosed with depression from study inception until March 31, 2023. Studies that compared acupressure with sham acupressure, conventional treatments (i.e., medication, usual care, etc.), and acupressure as an adjunct to conventional treatment for depression were included. The primary outcome was depression level measured using the Hamilton Depression Scale, Self-Rating Depression Scale, or Geriatric Depression Scale. A total of 19 RCTs involving 1686 participants were included. The pooled results showed that acupressure exhibited a significant beneficial effect on reducing the severity of depression compared with sham acupressure and served as an adjunct to conventional treatment, although the evidence level was moderate. Thus, acupressure may be a potential treatment for depression.
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Acupresión , Depresión , Humanos , Acupresión/métodos , COVID-19 , Depresión/terapia , Trastorno Depresivo/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.
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Terapia por Acupuntura , Artritis Experimental , Artritis Reumatoide , Ratones , Animales , Inflamación/patología , Citocinas/uso terapéutico , Antiinflamatorios/farmacología , Antígenos/efectos adversos , Edema/tratamiento farmacológicoRESUMEN
Recently, increasing numbers of studies have demonstrated that transient receptor potential ankyrin 1 (TRPA1) can be used as a potential target for the treatment of inflammatory diseases. TRPA1 is expressed in both neuronal and non-neuronal cells and is involved in diverse physiological activities, such as stabilizing of cell membrane potential, maintaining cellular humoral balance, and regulating intercellular signal transduction. TRPA1 is a multi-modal cell membrane receptor that can sense different stimuli, and generate action potential signals after activation via osmotic pressure, temperature, and inflammatory factors. In this study, we introduced the latest research progress on TRPA1 in inflammatory diseases from three different aspects. First, the inflammatory factors released after inflammation interacts with TRPA1 to promote inflammatory response; second, TRPA1 regulates the function of immune cells such as macrophages and T cells, In addition, it has anti-inflammatory and antioxidant effects in some inflammatory diseases. Third, we have summarized the application of antagonists and agonists targeting TRPA1 in the treatment of some inflammatory diseases.
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OBJECTIVES: Acupuncture has been found to be effective at relieving many inflammatory pain conditions, including rheumatoid arthritis (RA). We aimed to assess the anti-inflammatory potential of manual acupuncture (MA) treatment of RA using adjuvant-induced arthritic (AIA) rats and to explore the underlying mechanisms. METHODS: The anti-inflammatory and analgesic actions of MA at ST36 (Zusanli) in AIA rats were assessed using paw withdrawal latency and swelling, histological examination and cytokine detection by enzyme-linked immunoassay (ELISA). The cell-cell communication (CCC) network was analyzed with a multiplex immunoassay of 24 immune factors expressed in the inflamed joints, and the macrophage and Treg populations and associated cytokines regulated by MA were investigated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), ELISA and flow cytometry. RESULTS: MA markedly decreased heat hyperalgesia and paw swelling in AIA rats. MA-treated rats also exhibited decreased levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß) coupled with increased anti-inflammatory cytokines (IL-10, transforming growth factor (TGF)-ß1) in the ankle joints at protein and mRNA levels. CCC network analysis confirmed that macrophages are of critical importance and are potential therapeutic targets in RA. Repeated treatment with MA triggered a macrophage phenotypic switch in the paws, with fewer M1 macrophages. Prominent increases in the Treg cell population and TGF-ß1 in the popliteal lymph nodes demonstrated the immunomodulatory effects of MA. Furthermore, a selective TGF-ß1-receptor inhibitor, SB431542, attenuated the anti-inflammatory effects of MA and MA-induced suppression of the levels of M1-released cytokines. CONCLUSION: These findings provide novel evidence that the anti-inflammatory and analgesic effects of MA on RA act through phenotypic modulation involving the inhibition of M1 macrophage polarization and an increase in the Treg cell population, highlighting the potential therapeutic advantages of acupuncture in controlling pain and ameliorating inflammatory conditions.
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Terapia por Acupuntura , Artritis Experimental , Artritis Reumatoide , Ratas , Animales , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Factor de Crecimiento Transformador beta1 , Citocinas , Artritis Reumatoide/tratamiento farmacológico , Factor de Necrosis Tumoral alfa , Macrófagos/metabolismo , Macrófagos/patología , Dolor/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Artritis Experimental/tratamiento farmacológicoRESUMEN
In the past few decades, the use of acupuncture analgesia in clinical practice has increased worldwide. This is due to its various benefits, including natural alleviation of pain without causing various adverse effects associated with non-steroidal anti-inflammatory drugs (NSAID) and opioids. The acupoint represents the initial site of acupuncture stimulation, where diverse types of nerve fibers located at the acupoint hold significant roles in the generation and transmission of acupuncture-related information. In this study, we analyzed the patterns and mechanisms of acupuncture analgesic mediated by acupoint afferent fibers, and found that acupuncture stimulates acupoints which rapidly and directly induces activation of high-density primary afferent fibers under the acupoints, including myelinated A fibers and unmyelinated C fibers. During acupuncture stimulation at the muscle layer, the analgesic effects can be induced by stimulation of A fiber threshold intensity. At the skin layer, the analgesic effects can only be produced by stimulation of C fiber threshold intensity. Electroacupuncture (EA) activates A fibers, while manual acupuncture (MA) activates both A and C fibers. Furthermore, acupuncture alters acupoint microenvironments, which positively modulates afferent fibers, enhancing the transmission of analgesic signals. In addition to local activation and conduction at acupoints, nerve fibers mediate the transmission of acupuncture information to pain centers. In the spinal cord, acupuncture activates neurons by inducing afferent fiber depolarization, modulating pain gating, inhibiting long-term potentiation (LTP) of the spinal dorsal horn and wide dynamic range (WDR) neuronal activities. At higher nerve centers, acupuncture inhibits neuronal activation in pain-related brain regions. In summary, acupuncture inhibits pain signal transmission at peripheral and central systems by activating different patterns of afferent fibers located on various layers of acupoints. This study provides ideas for enhancing the precise application and clinical translation of acupuncture.
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The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture's actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS.
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Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.
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Terapia por Acupuntura , Puntos de AcupunturaRESUMEN
Cartilage damage is the key pathological mechanism in the progressive development of osteoarthritis(OA). Slowing down cartilage damage and accelerating cartilage repair are strategies for effective treatment of OA. Acupuncture and moxibustion therapies are widely used in relieving symptoms of OA and have a protective effect on cartilage. In this paper, we reviewed the mechanisms of acupuncture and moxibustion underlying relieving cartilage damage from three aspects: 1) promoting chondrocyte homeostasis by inhibiting apoptosis and improving cellular autophagy, 2) regulating extracellular matrix (ECM) metabolism (inhibiting decomposition and promoting synthesis) by suppressing the release of inflammatory factors and the activity of proteolytic enzymes, and 3) improving OA microenvironment by reducing the number of macrophagocyte 1 (M1) and increasing the ratio of M2/M1 in the local inflammatory locus. In addition, most studies on the mechanisms of acupuncture and moxibustion underlying remission of OA focus on the improvement of pathological changes, such as joint histopathology, cartilage morphology, synovial inflammatory reaction and infiltration, subchondral bone remodeling, etc., thus, the exact functions of acupuncture and moxibustion in ameliorating cartilage injury remain unknown. In view of the important role of mitochondrial dysfunction in promoting OA development and cartilage damage and the current use of tissue engineering methods of chondrocytes and mesenchymal stem cells to repair articular cartilage injury, it is highly recommended that future studies should pay more attention to these aspects.
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Terapia por Acupuntura , Cartílago Articular , Moxibustión , Osteoartritis , Condrocitos/metabolismo , Condrocitos/patología , Humanos , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/terapia , Péptido Hidrolasas/metabolismoRESUMEN
Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.
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Cisplatino/uso terapéutico , Electroacupuntura , Inmunomodulación , Neuroinmunomodulación , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/genética , Animales , Células de la Médula Ósea/metabolismo , Neutropenia Febril Inducida por Quimioterapia , Cisplatino/farmacología , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Electroacupuntura/métodos , Hematopoyesis/genética , Hematopoyesis/inmunología , Humanos , Inmunomodulación/genética , Leucopenia , Ratones , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/terapia , Neuroinmunomodulación/genética , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismoRESUMEN
OBJECTIVE: Chaihu Jia Longgu Muli decoction (CLMD) is widely used in the treatment of poststroke depression (PSD) in China. Some evidences show that it has advantages, but there lacks reliable evidence. This study aims to systematically evaluate the efficacy and safety of CLMD in the treatment of PSD. METHODS: All randomized controlled trials (RCTs) of CLMD in the treatment of PSD were searched from the following databases: PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Service System (CBM), from their inception to May 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 13 RCTs involving 1665 patients were finally included in this study, among which 5 RCTs were oral CLMD alone versus antidepressants, and 8 RCTs were oral CLMD with antidepressants versus antidepressants. Meta-analysis results showed that oral administration of CLMD could improve Hamilton's Depression Scale (HAMD) and the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) scores, improve the Barthel index, and have a low rate of adverse reactions, but there was no significant difference in the total effective rate (p=0.21 > 0.05) and the National Institute of Health Stroke Scale (NIHSS) score (p=0.47 > 0.05) between the antidepressants group and the oral administration of the CLMD group. Oral CLMD combined with antidepressants could improve the total effective rate, HAMD, and MESSS score, but there was no significant difference in Barthel index (p=0.06 > 0.05) and the adverse reaction rate (p=0.14 > 0.05) between the two groups. CONCLUSION: Current evidence suggests that oral CLMD alone or with antidepressants is more effective and safer in the treatment of PSD than oral antidepressants. Due to the limitation of the quality and quantity of the included studies, more high-quality studies are needed to confirm the above conclusion.
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Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.
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BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Acupuncture has been proven effective in RA treatment. This study aimed to investigate the anti-inflammatory action of acupuncture, specifically, in relation to immune cell interactions and key mediators. METHODS: Rats with adjuvant-induced arthritics (AIA) were treated with manual acupuncture (MA) at Zusanli (ST36). Joint edema and paw withdrawal latency were monitored to observe the effects on inflammation. The levels of 24 cytokines, chemokines, and growth factors in ankle joints during the treatment (on days 1, 7, 15, and 21) were detected by multiplex immunoassay. A bioinformatics analysis based on a directed weighted mathematical model was used to construct cell communication network diagrams and identify the key cells through calculation. The monocyte/macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines. RESULTS: ST36 MA alleviated paw edema and upregulated the nociceptive threshold of AIA rats. Several innate and adaptive immune cytokines were dynamically regulated by MA, and MA-treated rats showed a significant improvement in symptoms compared with AIA rats by day 21. The immune cell-cell communication networks were intensified with the development of RA but were significantly reduced after treatment with MA. MA was found to specifically regulate monocytes/macrophages in inflamed ankle joints ST36 MA also inhibited M1-phenotype macrophages accompanied by decreased levels of IL-1ß. CONCLUSIONS: ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. This research highlighted a systematic research paradigm for investigating mechanisms of acupuncture action.
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Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, ð¾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.
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Analgesia por Acupuntura/métodos , Neuroglía/metabolismo , Plasticidad Neuronal/fisiología , Manejo del Dolor/métodos , Dolor/metabolismo , Analgesia por Acupuntura/tendencias , Animales , Citocinas/inmunología , Citocinas/metabolismo , Humanos , Neuroglía/inmunología , Dolor/inmunologíaRESUMEN
Due to its own internal laws of development, Chinese medicine (CM) seems more inclined to empirical medicine in a relatively long historical period. It is considered to be lacking objective and unified clinical practice guidelines (CPGs), and the difficulties in diagnosis and therapeutic effect evaluation comes with it, have restricted its further inheritance, development and international communication. Over the years, our research group has been committed to improving the standardization theory and methodology of CM, also perfecting relative techniques for further application, which are all based on the stratified evidence scoring method. We have already applied this method to 45 issued guidelines, including 5 national guidelines, 3 industrial guidelines, and 37 formulation/revision social organization guidelines. The stratified evidence scoring method has been recognized and used widely. It helps scholars and applicators to study, formulate, publish and popularize the acupuncture therapy clinical practice guidelines better, thus further promotes the development of acupuncture therapy.
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Terapia por Acupuntura , Acupuntura , Medicina Tradicional de Asia Oriental , Guías de Práctica Clínica como Asunto , Proyectos de InvestigaciónRESUMEN
Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed. METHODS: We searched the PubMed database for studies with keywords including ["berberine"] and ["tumor" or "cancer"] and ["AMPK"] or ["AKT"] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine. RESULTS: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine. CONCLUSION: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.
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Berberina , Proteínas Proto-Oncogénicas c-akt , Proteínas Quinasas Activadas por AMP , Adenosina Monofosfato , Berberina/farmacología , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-QuinasasRESUMEN
A fresh strategy based on two-step electrochemical reduction for the fabrication of palladium nanoparticles/reduced oxide nanocomposite-modified glass carbon electrode (PdNPs/rGO/GCE) was established in this study. Field emission scanning electron microscopy (FESEM) images showed that spherical PdNPs were evenly distributed on the surface of rGO-modified electrode (rGO/GCE), and the introduction of PdNPs has no effect on the morphology of rGO. Electrochemical impedance spectroscopy (EIS) studies revealed that the conductivity of PdNPs/rGO/GCE was higher than that of rGO/GCE and bare GCE. The electrochemical performances of PdNPs/rGO/GCE sensor were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry using ascorbic acid (AA), dopamine (DA), and uric acid (UA) as analytes. At the optimized conditions, wide linear ranges of 0.5-3.5 mM (R 2 = 0.99), 3-15 µM (R 2 = 0.99) and 15-42 µM (R 2 = 0.99), and 0.3-1.4 mM (R 2 = 0.99) towards AA, DA, and UA in ternary mixture were observed, respectively. In addition to superior anti-interference capability, fast response (≤5 s), excellent reproducibility, and good long-term stability were also given by this sensor. These results suggested that PdNPs/rGO/GCE is promising for the simultaneous detection of AA, DA, and UA in practical application.
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BACKGROUND: Obsessive-compulsive disorder is common, chronic mental disorder, which is characterized by recurrent, unwanted, or intrusive thoughts and repetitive behaviors or mental action. Acupuncture and moxibustion, as a popular form of complementary and alternative therapy, have the advantages of low side effects, high safety, and low cost. The research showed that acupuncture and moxibustion have a good clinical efficacy on obsessive-compulsive disorder. However, there is no literature to systematically evaluate the efficacy and safety of acupuncture and moxibustion in treating obsessive-compulsive disorder. Thus, this study is aimed to evaluate the efficacy and safety of acupuncture and moxibustion for obsessive-compulsive disorder patients, providing reliable evidence for clinical application. METHODS: Randomized controlled trials of acupuncture and moxibustion combined with western medicine for the treatment of obsessive-compulsive disorder will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure(CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) from inception to June, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies dependently. Statistical analysis is performed in RevMan 5.3 software. RESULTS: The efficacy and safety of acupuncture and moxibustion combined with western medicine for obsessive-compulsive disorder will be assessed based on the total effective rate, Hamilton Anxiety Scale score, Hamilton Rating Scale for Depression score, Clinical Global Impression score, side effects, and so on. CONCLUSIONS: The proposed systematic review and meta-analysis of acupuncture and moxibustion combined with western medicine for treating obsessive-compulsive disorder is expected to provide reliable evidence for clinical application. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/CDGTW.