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BACKGROUND: Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. METHODS: This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100â mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. RESULTS: Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. CONCLUSIONS: Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. TRIAL REGISTRATION: ISRCTN.org Identifier 13563102.
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Terapia por Acupuntura , Trastornos Migrañosos , Topiramato , Humanos , Topiramato/uso terapéutico , Topiramato/administración & dosificación , Trastornos Migrañosos/prevención & control , Trastornos Migrañosos/terapia , Femenino , Masculino , Persona de Mediana Edad , Adulto , Terapia por Acupuntura/métodos , Enfermedad Crónica , Resultado del Tratamiento , Método Simple Ciego , Adulto Joven , Terapia Combinada/métodos , Adolescente , AncianoRESUMEN
Neurturin (NRTN) is one of the glial cell line-derived neurotrophic factor family ligands crucial for neuron growth, differentiation and maintenance. Recent studies showed NRTN promotes an aggressive pancreatic cancer phenotype, and predicts shorter survival in lung cancer patients. However, its expression and function in colorectal cancer (CRC) remain unclear. Herein, we found NRTN was enriched in CRC cells, and predicted poor patients outcomes. Upregulated NRTN enhanced the migration and invasion of CRC cells and vascularization of endothelial cells. In mechanism, NRTN promoted ZEB1/N-cadherin and vascular endothelial growth factor (VEGF)-A expression in CRC cells, which were responsible for tumor cell motility and angiogenesis, respectively. More importantly, NRTN inhibition prevented CRC metastasis and angiogenesis in vivo. In conclusion, NRTN promotes CRC cells motility and tumor angiogenesis via inducing ZEB1/N-cadherin and VEGF-A overexpression. It is a potential therapeutic target and negative prognostic biomarker for CRC patients.
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Isoflurane, a common volatile anesthetic, has been widely used to provide general anesthesia in operations. However, exposure to isoflurane may cause widespread neurotoxicity in the developing animal brain. Fraxetin, a natural coumarin derivative extracted from the bark of Fraxinus rhynchophylla, possesses versatile pharmacological properties including anti-oxidative, anti-inflammatory, and neuroprotective effects. However, the effect and action mechanism of fraxetin on neurotoxicity induced by isoflurane are unknown. Reactive oxygen species (ROS) generation, cell viability, lactate dehydrogenase (LDH) release, and apoptosis were estimated by 2',7'-dichlorofluorescin-diacetate (DCFH-DA) staining, MTT, LDH release, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining assays, respectively. The protein levels of light chain 3 (LC3)-I, LC3-II, p62, protein kinase B (Akt), and phosphorylated Akt (p-Akt) were detected by western blot analysis. Isoflurane induced ROS, LDH release, apoptosis, and autophagy, but inhibited the viability in HT22 cells, which were overturned by fraxetin or ROS scavenger N-acetyl-L-cysteine. Fraxetin suppressed isoflurane-induced PI3K/Akt inactivation in HT22 cells. PI3K/Akt inactivation by LY294002 resisted the effects of fraxetin on isoflurane-induced autophagy and autophagy-modulated neurotoxicity in HT22 cells. In conclusion, fraxetin suppressed ROS-dependent autophagy by activating the PI3K/Akt pathway to inhibit isoflurane-induced neurotoxicity in hippocampal neuronal cells.
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Isoflurano , Síndromes de Neurotoxicidad , Animales , Apoptosis , Autofagia , Cumarinas/metabolismo , Cumarinas/farmacología , Hipocampo , Isoflurano/metabolismo , Isoflurano/toxicidad , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide, with a poor prognosis. The aim of our study was to identify key biomarkers and their associations with immune cells to aid in the study of IgAN pathology and immunotherapy. Material and methods: The data of IgAN were downloaded from a public database. The metaMA package and limma package were used to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs), respectively. Biological functions of the DEmRNAs were analyzed. Machine learning was used to screen the mRNA biomarkers of IgAN. Pearson's correlation coefficient was used to analyze the correlation between mRNA biomarkers, immune cells and signaling pathways. Moreover, we constructed a miRNAs-mRNAs targeted regulatory network. Finally, we performed in vitro validation of the identified miRNAs and mRNAs. Results: 1205 DEmRNAs and 125 DEmiRNAs were identified. In gene set enrichment analysis (GSEA), tumor necrosis factor α (TNF-α) signaling via nuclear factor κB (NF-κB), apoptosis and MTORC-1 signaling were inhibited in IgAN. 8 mRNA biomarkers were screened by machine learning. In addition, the distribution of 8 immune cell types was found to be significantly different between normal controls and IgAN by difference analysis. Pearson correlation coefficient analysis demonstrated that AKAP8L was significantly negatively correlated with CD4+ memory T-cells. AKAP8L was also significantly negatively correlated with TNF-α signaling via NF-κB, apoptosis, and MTORC-1 signaling. Subsequently, 5 mRNA biomarkers predicted corresponding negative regulatory miRNAs. Conclusions: The identification of 8 important biomarkers and their correlation with immune cells and biological signaling pathways provides new ideas for further study of IgAN.
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Propofol, a general intravenous anesthetic, has been demonstrated to cause a profound neuroapoptosis in the developing brain followed by long-term neurocognitive impairment. Our study aimed to examine the neuroprotective effect of neuronal PAS domain protein 4 (NPAS4), an activity-dependent neuron-specific transcription factor, on propofol-induced neurotoxicity in hippocampal neuronal HT22 cells. The differentially expressed genes in HT22 cells after treatment with propofol were screened from Gene Expression Omnibus dataset GSE106799. NPAS4 expression in HT22 cells treated with different doses of propofol was investigated by qRT-PCR and Western blot analysis. Cell viability, lactate dehydrogenase (LDH) release, caspase-3 activity, and apoptosis were evaluated by MTT, a LDH-Cytotoxicity Assay Kit, a Caspase-3 Colorimetric Assay Kit, and TUNEL assay, respectively. The protein levels of LC3-I, LC3-II, Beclin 1, p62 and NPAS4 were detected using Western blot analysis. Propofol treatment concentration-dependently decreased NPAS4 expression in HT22 cells. Propofol treatment inhibited cell viability, increased LDH release and caspase-3 activity, and induced apoptosis and autophagy in HT22 cells. NPAS4 overexpression suppressed propofol-induced cell injury and autophagy in HT22 cells. Mechanistically, autophagy agonist rapamycin attenuated the neuroprotective effect of NPAS4 in propofol-treated HT22 cells. In conclusion, NAPS4 overexpression protected hippocampal neuronal HT22 cells against propofol-induced neurotoxicity by reducing autophagy.
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Autofagia/fisiología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Propofol/toxicidad , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hipocampo/metabolismo , RatonesRESUMEN
BACKGROUND: Temporomandibular disorders (TMD) is the leading cause of pain and disability among frequently occurring facial pain and the second leading cause of musculoskeletal conditions. AIM: We examined whether acupuncture could alleviate pain intensity in patients with temporomandibular disorders (TMD). DESIGN AND METHODS: Sixty participants with TMD were randomly assigned (ratio 1:1) to receive three acupuncture or sham acupuncture sessions weekly for 4 weeks. The primary outcome was the change in the mean weekly pain intensity from baseline to week 4. Secondary and exploratory outcomes included proportion of participants with ≥30% or ≥ 50% reduction in pain intensity, change in jaw opening and movement, graded chronic pain scale, jaw functional limitations scale-20-item, Depression, Anxiety and Stress Scales-21, Pittsburgh sleep quality index at week 4 and 8, and the pressure pain threshold and surface electromyography at week 4. RESULTS AND CONCLUSION: The acupuncture group showed significantly reduced pain intensity compared to the sham group at week 4 (-1.49, 95% confidence interval [CI]: -2.32 to -0.65; P < 0.001) and week 8 (-1.23, 95% CI: -2.11 to -0.54; P = 0.001). Acupuncture's effectiveness surpassed sham's at 4 weeks and lasted 8 weeks. Participants in the acupuncture group experienced significantly greater improvements in the 30% and 50% response rate, jaw opening and movement, GCPS, JFLS-20, DASS-21 and PSQI than those in the sham acupuncture group. There were no significant between-group differences in PPT and sEMG. In summary, acupuncture provided marked pain relief and improvement in physical and emotional function for patients with TMD compared with sham acupuncture.
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Background: Ectopic adrenocortical tissues and neoplasms are rare and usually found in the genitourinary system and abdominal cavity. The thorax is an extremely rare ectopic site. Here, we report the first case of nonfunctional ectopic adrenocortical carcinoma (ACC) in the lung. Case presentation: A 71-year-old Chinese man presented with vague left-sided chest pain and irritable cough for 1 month. Thoracic computed tomography revealed a heterogeneously enhancing 5.3 × 5.8 × 6.0-cm solitary mass in the left lung. Radiological findings suggested a benign tumor. The tumor was surgically excised upon detection. Histopathological examination using hematoxylin and eosin staining showed that the cytoplasm of the tumor cells was rich and eosinophilic. Immunohistochemical profiles (inhibin-a+, melan-A+, Syn+) indicated that the tumor had an adrenocortical origin. The patient showed no symptoms of hormonal hypersecretion. The final pathological diagnosis was non-functional ectopic ACC. The patient was disease-free for 22 months and is still under follow-up. Conclusions: Nonfunctional ectopic ACC in the lung is an extremely rare neoplasm that can be easily misdiagnosed as primary lung cancer or lung metastasis, both preoperatively and on postoperative pathological examination. This report may provide clues to clinicians and pathologists regarding the diagnosis and treatment of nonfunctional ectopic ACC.
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Background: Radiotherapy usually leads to a decrease in the total number of lymphocytes in patients with esophageal cancer. The factors that causing lymphopenia and the clinical significance of lymphopenia are studied in this article. Patients and methods: 110 patients with esophageal squamous cell carcinoma who had undergo intensity-modulated radiation therapy were enrolled. Statistical methods were used to analyze the correlation between lymphopenia and total survival in patients with esophageal cancer during radiotherapy, and analyze the correlations between nutritional factors and lymphopenia. Results: There were 11 patients with the lowest lymphocyte value with level 1-2 during radiotherapy, accounting for 10% of all the patients, and 110 patients with level 3-4, accounting for 90% of all the patient. In all the enrolled patients, the incidence of lymphocyte nadir G1, G2, G3 and G4 MinALC during radiotherapy accounted for 0.91%, 9.09%, 62.73% and 27.27%, respectively.KM survival analysis showed that the overall survival of patients in the group (MinALC ≤ 0.41×109/L) was significantly lower than that of the patients in the other group (MinALC>0.43×109/L). Nutritional indicators were positively correlated with the decline degree of lymphocytes. The minimal value of lymphocyte can predict the occurrence of grade 3-4 radiation pneumonitis. Conclusion: Lymphopenia induced by radiotherapy can predict survival and radiation pneumonitis. Nutritional factors such as hemoglobin and albumin were positively correlated with total lymphocytes numbers induced by radiotherapy.
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OBJECTIVE: To observe the clinical therapeutic effect on post-stroke dysphagia treated with He's santong (triple promotion) acupuncture therapy through surface electromyography (sEMG). METHODS: A total of 60 patients with post-stroke dysphagia were divided into a routine treatment group and a He's santong acupuncture therapy group, using blocked randomization, 30 cases in each one. In the routine treatment group, the secondary prevention and swallowing rehabilitation training were adopted. In the He's santong acupuncture therapy group, on the base of the treatment as the routine treatment group, weitong (mild promotion, routine acupuncture at bilateral Fengchi ï¼»GB20ï¼½, Fengfu ï¼»GV16ï¼½, Yifeng ï¼»TE17ï¼½, Lianquan ï¼»CV23ï¼½, Jia-lianquan ï¼»Extraï¼½, Fenglong ï¼»ST40ï¼½ and Tongli ï¼»HT5ï¼½, needle retaining for 30 min, 5 treatments a week), wentong (warm promotion, pricking with fire needle at bilateral GB20 and CV23, twice a week) and qiangtong (strong promotion, blood-letting with three-edge needle at Jinjin ï¼»EX-HN12ï¼½, Yuye ï¼»EX-HN13ï¼½ and Yanhoubi ï¼»Extraï¼½, twice a week) treatment was added. The therapy was given consecutively for 4 weeks in each group. The score of fiberoptic endoscopic examination of swallowing (FEES) and Rosenbek-penetration-aspiration scale (PAS), the score of swallowing grading scale, the score of the modified Mann assessment of swallowing ability (MMASA) and the peak amplitude of sEMG were recorded before and after treatment in patients. RESULTS: Compared with before treatment, the score of FEES and PAS after treatment was decreased (P<0.05), the scores of swallowing grading scale and MMASA after treatment were increased in both routine treatment group and He's santong acupuncture therapy group (P<0.05), the peak amplitude of sEMG was increased (P<0.05) in the He's santong acupuncture therapy group and decreased (P<0.05) in the routine treatment group. Compared with the routine treatment group, the score of FEES and PAS was decreased (P<0.05), the scores of swallowing grading scale and peak amplitude of sEMG were increased in the He's santong acupuncture therapy group (P<0.05). CONCLUSION: He's santong acupuncture therapy is obviously effective on post-stroke dysphagia, which may be related to its effects in increasing the contraction of swallowing-related muscles and improving the peak amplitude of hyoid muscle group.
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Terapia por Acupuntura , Trastornos de Deglución , Deglución , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Electromiografía , Humanos , Resultado del TratamientoRESUMEN
Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). Patients and methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6. Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3. Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. Clinical trial registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606].