ABSTRACT
BACKGROUND@#Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.@*OBJECTIVE@#To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.@*METHODS@#Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.@*CONCLUSION@#Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).
Subject(s)
Pregnancy , Female , Humans , Live Birth , Fertilization in Vitro/methods , Pregnancy Outcome , Abortion, Spontaneous , Acupuncture TherapyABSTRACT
BACKGROUND@#Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.@*OBJECTIVE@#To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.@*METHODS@#Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.@*RESULTS@#A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.@*CONCLUSIONS@#Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).
ABSTRACT
The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox intervention measures, but also the operational elements of Acup-Mox. This paper aimed to put forward the idea and process of collecting clinical questions in developing international acupuncture clinical practice guidelines. The experience was collected and the idea of collecting clinical questions of Acup-Mox was formed through expert consultation and discussion in combination with expert opinions. Based on the characteristics of Acup-Mox discipline. This paper put forward the thinking of collecting elements of clinical questions following the intervention-population-outcome-control (I-P-O-C) inquiry process, according to the discipline of Acup-Mox. It was emphasized that in the process of collecting clinical questions, "treatable population" and "alleviable outcome indicators" for a specific Acup-Mox intervention with certain therapeutic effect should be focused on, so as to highlight the pertinence of clinical questions of Acup-Mox guidelines in terms of population and outcome elements.
Subject(s)
Moxibustion , Acupuncture Therapy , AcupunctureABSTRACT
Pulmonary fibrosis is end-stage of variety of heterogeneous interstitial lung disease, characterizedby excessive proliferation of fibroblasts and extracellular matrix deposition and destruction of lung parenchyma. Thyroid and lung are derived from the same endodermal cells, thyroid hormone affect the occurrence、development and prognosis of the chronic obstructive pulmonary disease, lung cancer and other lung diseases, This article reviews the role and mechanism of thyroid hormone in pulmonary fibrosis in order to provide new idea for the study of the role and mechanism of thyroid hormone in silicosis.
Subject(s)
Humans , Pulmonary Fibrosis/pathology , Lung/pathology , Silicosis , Lung Diseases, Interstitial , Fibroblasts , Thyroid Hormones , FibrosisABSTRACT
The commonly used terms "sham acupuncture" and "placebo acupuncture" in clinical acupuncture research is compared and analyzed in this article. In terms of their respective characteristics, sham acupuncture has a wider scope, including various types of acupoints, needle insertion at non-acupoint or non-insertion at acupoints, while placebo acupuncture mainly focuses on non-insertion at acupoints. Sham acupuncture mainly emphasizes the appearance similarity to real acupuncture, while placebo acupuncture emphasizes both similarity in appearance and the absence of therapeutic effects. Properly distinguishing and applying sham acupuncture and placebo acupuncture can help standardize their usage in terminology. Considering the difficulty in setting up qualified placebo acupuncture, it is suggested that researchers use the term "sham acupuncture" to describe the acupuncture control methods used in clinical research.
Subject(s)
Humans , Acupuncture Therapy , Needles , Research Personnel , Clinical Trials as TopicABSTRACT
In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.
Subject(s)
Acupuncture Therapy , Acupuncture/education , Moxibustion , Acupuncture Points , KnowledgeABSTRACT
This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.
Subject(s)
Acupuncture Therapy , Acupuncture , Research Design , ConsensusABSTRACT
BACKGROUND@#The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.@*OBJECTIVE@#This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.@*SEARCH STRATEGY@#PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.@*DATA EXTRACTION AND ANALYSIS@#Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.@*RESULTS@#Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.@*CONCLUSION@#Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
Subject(s)
Female , Humans , Dysmenorrhea/therapy , Acupuncture Therapy , Pain Management , Needles , Placebo EffectABSTRACT
The paper analyzes the specificity of term recognition in acupuncture clinical literature and compares the advantages and disadvantages of three named entity recognition (NER) methods adopted in the field of traditional Chinese medicine. It is believed that the bi-directional long short-term memory networks-conditional random fields (Bi LSTM-CRF) may communicate the context information and complete NER by using less feature rules. This model is suitable for term recognition in acupuncture clinical literature. Based on this model, it is proposed that the process of term recognition in acupuncture clinical literature should include 4 aspects, i.e. literature pretreatment, sequence labeling, model training and effect evaluation, which provides an approach to the terminological structurization in acupuncture clinical literature.
Subject(s)
Acupuncture Therapy , Electronic Health Records , Natural Language ProcessingABSTRACT
The progress of Chinese clinical research on acupuncture and moxibustion in recent 10 years was reviewed and analyzed, and corresponding suggestions were put forward for the current problems. In the past 10 years, Chinese clinical research on acupuncture and moxibustion has made considerable progress, mainly in the following areas: a series of internationally recognized clinical research evidences have been published, a preliminary acupuncture clinical evaluation system has formed, sham/placebo acupuncture control is widely used internationally, acupuncture clinical research norms and standards have been initially established. However, the following issues still need to be paid attention to in follow-up research: focus on the overall layout and refinement of clinical research, further improvement of clinical evaluation system, developing relevant norms for sham/placebo acupuncture setting and reporting, strengthening data sharing and platform integration, building a smooth basic and two-way transformation clinical pathway, etc.
Subject(s)
Acupuncture , Acupuncture Therapy , Medicine, Chinese Traditional , Moxibustion , PublicationsABSTRACT
Objective: To evaluate the value of the age-adjusted Charlson comorbidity Index (ACCI) in predicting the prognosis and guiding the clinical treatment of laryngeal squamous cell carcinoma (LSCC) in patients over 60 years old. Methods: Retrospective analysis of 249 cases of LSCC in Shanxi Provincial Cancer Hospital and First Hospital of Shanxi Medical University from 2008 to 2015 was performed. There were 234 males and 15 females, aged from 60 to 88 years. The clinical characteristics, treatment information and follow-up data were collected. ACCI was used to score the comorbidities of the patients. Receiver operating characteristic (ROC) curve was drawn and the patients were divided into high ACCI group and low ACCI group according to the cut-off value of ACCI. Prognostic factors were analyzed. Kaplan-Meier method was used for survival analysis, rank sum test was used for comparison between groups, χ2 test was used for enumeration data. Results: Overall survival (OS) was 54.6%, progression-free survival (PFS) was 59.4%, and cancer-specific survival (CSS) was 58.6%. Both the median survival time and PFS time were 60 months. The best cutoff point of the ACCI group was 5. Cox multivariate analysis showed that ACCI was an independent risk factor for OS, PFS and CSS (OR=1.553, 1.499 and 1.534,respectively, all P<0.05). In the high ACCI group, OS (χ2=4.120 and 4.115,P<0.05) and CSS (χ2=4.510 and 5.009,P<0.05) of patients treated with surgery plus radiotherapy and patients with radiotherapy alone were better than those of patients with surgery alone (P<0.05). But in the low ACCI group, there was no significant difference in prognosis among the three treatment regimens (P>0.05). Conclusion: High ACCI offors important prognostic information for LSCC in patients over 60 years old, and can guide clinical treatment options.
Subject(s)
Female , Humans , Male , Middle Aged , Age Factors , Comorbidity , Head and Neck Neoplasms , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and NeckABSTRACT
OBJECTIVE@#To explore the rule of point selection in treatment of cerebral palsy with acupuncture in preschool children.@*METHODS@#Based on the electronic medical records of Xi'an Encephalopathy Hospital of TCM, through structuring medical record text, acupuncture prescriptions were extracted. Using the data mining tools of the ancient and modern medical record cloud platform V2.2.3 and the clinical effective prescription and molecular mechanism analysis system of traditional Chinese medicine V2.0, the cluster analysis and complex network analysis were conducted on acupuncture prescriptions.@*RESULTS@#Of 1584 acupuncture prescriptions for cerebral palsy in children, there were 84 acupoints and stimulating areas of scalp acupuncture, of which, foot-motor-sensory area, balance area and Sanyinjiao (SP 6) were the top 3 acupoints with the highest use rate. With cluster analysis, 5 groups of common supplementary acupoints and stimulating areas were found, named, Weizhong (BL 40) and Waiguan (TE 5), Shousanli (LI 10), Xingjian (LR 2), Xuanzhong (GB 39) and Chengfu (BL 36), foot-motor-sensory area, balance area and Sanyinjiao (SP 6), Xuehai (SP 10) and Fenglong (ST 40), Pishu (BL 20), motor area and Yanglingquan (GB 34). With complex network analysis on core prescriptions, 13 core acupoints and stimulating areas of scalp acupuncture were obtained, including 3 core main points, i.e. Sanyinjiao (SP 6), balance area and foot-motor-sensory area and 10 sub-core points, i.e. Taichong (LR 3), motor area, Xuehai (SP 10), Ganshu (BL 18), Pishu (BL 20), Yanglingquan (GB 34), Sishencong (EX-HN 1), Baihui (GV 20), Fengchi (GB 20) and Shenshu (BL 23).@*CONCLUSION@#In treatment of acupuncture for cerebral palsy in preschool children, the core prescriptions reveal the simultaneous treatment of exterior and interior, the mutual regulation of
Subject(s)
Child, Preschool , Humans , Acupuncture Points , Acupuncture Therapy , Cerebral Palsy/therapy , Data Mining , Electronic Health RecordsABSTRACT
On the base of the idea of traditional Chinese medicine as "disease prevention", the mode and the protocol of the moxibustion intervention for the group under quarantine after close contact with coronavirus disease 2019 (COVID-19) were explored. The group under quarantine after close contact with COVID-19 was taken as the subjects. By the non-contact physician-patient communication network platform co-developed by China Association of Acupuncture-Moxibustion, Hunan Provincial Association of Acupuncture-Moxibustion, Data Center of China Academy of Chinese Medical Sciences and Yuge Medicine Company, an exploratory randomized controlled trial was designed. A total of 100 cases were included and randomized into a moxibustion group and a conventional intervention group, 50 cases in each one. In the moxibustion group, moxibustion intervention was used. In the conventional intervention group, the conventional observation was adopted without moxibusiton intervention applied. The outcomes included the symptoms changes, e.g. anxiety, emotional disturbance, fatigue, headache and diarrhea, as well as whether quarantine release and the case confirmed or not, etc. The results were evaluated before intervention, in 14 days of intervention and 2 weeks after intervention separately. In this research, on the base of internet plus technology and with the internet communication platform adopted, through mobile phone WeChat App, it was to implement the subject screen, the random allocation and the instruction of moxibustion intervention as well as the quality control of patient's diary and data collection. It is anticipated that the significance and the implementation mode of moxibustion intervention can be assessed preliminarily for the group under quarantine after close contact with COVID-19.
Subject(s)
Humans , Acupuncture Therapy , Methods , Betacoronavirus , China , Coronavirus Infections , Therapeutics , Moxibustion , Pandemics , Pneumonia, Viral , Therapeutics , QuarantineABSTRACT
Acupuncture and moxibustion has a wealth of experience in the prevention and control of epidemic disease since ancient times, which was used for all kinds of acute infectious diseases in modern times and its efficacy has been clearly and reliably reported. This article proposes the theoretical feasibility and reliability of acupuncture and moxibustion interventional prevention and treatment by discussing the recognition of coronavirus disease 2019 (COVID-19) from the perspective of acupuncture and moxibustion. The unique "acupuncture and moxibustion program" for COVID-19 is presented including treatment in different stages, selecting acupoints by distinguishing meridians, applying needle technique by various methods. The article also proposes a new understanding of acupuncture and moxibustion at related acupoints on the surface of the body that can directly affect the "" to treat the disease.
Subject(s)
Humans , Acupuncture Therapy , Betacoronavirus , Coronavirus Infections , Therapeutics , Moxibustion , Pandemics , Pneumonia, Viral , Therapeutics , Reproducibility of ResultsABSTRACT
To explore the basic principles and methods of quality control of clinical registry research in the field of acupuncture. This study drawed on the data quality control methods of clinical trials in the United States and combined clinical practice experience, based on the "International Patient Registry Platform of Acupuncture and Moxibustion", and the registry study of acupuncture treatment for early-onset ovarian insufficiency as a model. The principles of accuracy, authenticity, consistency and completeness were followed. A remote and on-site quality control method with remote quality control as the main and on-site quality control as the supplement is formed, with a view to providing ideas and reference for the quality control of registry research.
Subject(s)
Humans , Acupuncture Therapy , Clinical Trials as Topic , Reference Standards , Moxibustion , Quality Control , RegistriesABSTRACT
As a discipline, the independent knowledge system of acupuncture-moxibustion has been established in - Dynasties, while the education and management institutes have tended to be formalized since Northern and Southern Dynasties and continue to late imperial period. In the period of the Republic of China, acupuncture-moxibustion discipline began to be constructed intentionally, and the knowledge system, education institutes and institution have changed significantly with the characteristics of modern science. Now acupuncture has fully met the conditions of modern subjects. The study of the history of acupuncture-moxibustion discipline needs the perspective of internal and external history integration, focusing on the differences from academic history and educational history. In addition, four important topics in the current research of the history of acupuncture-moxibustion discipline are suggested: the relationship between acupuncture- moxibustion discipline and related disciplines, scientific value and technology philosophy, international recognition and branch disciplines.
Subject(s)
Acupuncture Therapy , History , China , History, Ancient , Moxibustion , HistoryABSTRACT
Objective:To study the effect of Yupingfeng San （YPFS） on the expressions of GATA binding protein 3 （GATA3） and forkhead transcription factor3 （Foxp3） in ovalbumin （OVA）-induced lung tissue of allergic rhinitis （AR） mice， and explore the mechanism of YPFS on AR. Method:The allergic rhinitismice model was established by intraperitoneally injecting with OVA and Al （OH）3， and challenged with OVA intranasally. The mice were divided into four groups： normal，model，chloretadine（3 mg·kg-1） and YPFS（6.5 g·kg-1） group， the corresponding drugs were orally administrated for three weeks. At the end of administration，the infiltration of inflammatory cells， such as mast cells， eosinophils and neutrophils in nasal mucosa， were observed by htoxylin eosin （HE） staining. The serum concentrations of OVA-specific IgE and cytokines ［interleukin-4（IL-4）， IL-5 and γ-interferon （INF-γ）］ were determined by enzyme-linked immune sorbent assay （ELISA）. The expressions of GATA3 and Foxp3 proteins in nasal mucosa tissue were detected by Western blot. Result:The AR mice had such symptoms as scratching， sneezing and running nose. Nasal mucosa section by HE staining showed significant desquamation of AR mouse nasal mucosa cilia， obvious tissue stromal edema， telangiectasia， and a large number of eosinophilic cells， lymphocytes， plasma cells infiltration. YPFS obviously improved nasal symptoms of allergic rhinitis mice. Nasal mucosa epithelial structure was complete and arranged evenly， with no obvious tissue clearance edema and vasodilation， and inflammatory cell infiltration was significantly reduced. Compared with normal group， the levels of OVA specific IgE， IL-4 and IL-5 in peripheral blood of AR model group were significantly higher（P<0.01）， and the INF-γ level was significantly lower （P<0.01）. Compared with AR model group， the administration of chloretadine and YPFS can significantly reduce the level of OVA specific IgE and IL-4， IL-5， and increase the level of INF-γ in AR mice peripheral blood （P<0.05， P<0.01）. Western blot results showed that compared with normal group， GATA3 protein expression was significantly increased， while Foxp3 protein expression was significantly decreased in AR model group （P<0.05， P<0.01）. Compared with AR model group， YPFS inhibited GATA3， and promoted Foxp3 protein expression （P<0.01）. Conclusion:YPFS has an effect in alleviating OVA-induced allergic rhinitis．YPFS may modulate the immune response by regulating the balance of Th2/Treg cells.
ABSTRACT
Objective:To explore the potential mechanisms of Panax Notoginseng Saponins （PNS） on growth inhibition of breast cancer cell line 4T1 in tumor-bearing mice by investigating the mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways. Method:The 4T1 breast cancer mice model was established. Forty-eight mice with successful modeled and randomly divided into the low， medium and high-dose PNS groups （10， 20， 40 mg·kg-1） and the model control group （12 mice in each group）. The PNS groups received intraperitoneal injection with dosage of 10 mL·kg-1， while the controlled group was given the same dosage of saline. After administration with PNS for 28 days， tumor tissues were isolated， weighed， sliced and homogenized. Tumor cell apoptosis was detected by TdT mediated-dUTP nick end labeling （TUNEL） staining. The mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by Real-time polymerase chain reaction（Real-time PCR）. The protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by immunofluorescence staining and Western blot. Result:Compared with model group， the tumor weights of medium-dose and high-dose PNS groups were decreased significantly （P<0.05）. TUNEL staining showed that the number of apoptotic tumor cells increased with the rise of dosage of PNS （P<0.05）. The medium-dose and high-dose PNS groups showed a significant increase in the mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 as well as the protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissues （P<0.05）， with statistically significant differences （P<0.05）. Conclusion:PNS could inhibit the tumor growth of breast cancer cell line 4T1 in tumor-bearing mice， which may be related to the activation of MEKK1/SEK1/JNK1/AP-1 signaling pathways.
ABSTRACT
@#【Objective】 To use next generation sequencing （NGS） for examing 295 gene mutations in Chinese mucosal melanoma，and explore the mutation landscape of Chinese mucosal melanoma for potential therapeutic targets. 【Methods】The specimens were from 25 mucosal melanoma patients from September 2017 to September 2018 in Biotherapy Center，Sun Yat-sen University Cancer Center. Mutations of 295 genes were detected by NGS sequencing in the Department of Molecular Diagnostics in our hospital. 【Results】 The mutation frequency of major driver genes of melanoma was：BRAF 20%（5/25），KIT 20%（5/25），NRAS 12%（3/25），and NF1 8%（2/25），respectively. The most common mutation was an increase copy number in MYC（9/25，36%），followed by an increase in KDR copy number，24%（6/25）. DNA damage repair，cell cycle，PI3K-mTOR，growth factor receptor，MAPK，immune response and WNT/NOTCH related pathways were widely mutated. Mutation rates were 76%（19/25），72%（18/25），56%（14/25），60%（15/25），36%（9/25），28%（7/25），and 24%（6/25），respectively. Multiple therapeutic targets were observed，such as ATM，ATRX，EMSY， FANCI，RAD52，MET，PDGFRA，KDR，FLT4，ALK，ERBB3 and ROS1.【Conclusion】Gene mutations in Chinese mucosal melanoma were different from that of Chinese cutaneous melanoma and that of Caucasians. NGS could provide potential therapeutic targets for the treatment of Chinese mucosal melanoma.
ABSTRACT
@#【Objective】The aim of this study was to investigate the effect and mechanism of cabozantinib combined with anti-PD-L1 antibody on the growth of subcutaneous transplanted malignant melanoma in mice.【Methods】Established mouse subcutaneous xenograft model using mouse melanoma cell line B16- F10，and then randomly divided into five groups：saline control group，vehicle control group，anti PD- L1 antibody group，cabozantinib group，cabozantinib in combined with anti- PD- L1 antibody group （combination group）. Tumor growth was observed and tumor volume was measured every 2 days. The research endpoint was defined as when the tumor volume reached 2 000 mm3 or the difference between the groups was statistically significant. Then the mice were sacrificed and tissue samples were taken at the endpoint of the study. Infiltrating immune cells including CD4 + ，CD8 + T lymphocytes and myelogenous suppressor cells （MDSC）were detected by flow cytometry. In addition，B16-F10 cells cultured in vitro were treated with different drugs， the apoptosis was detected by flow cytometry ，and the protein expressions of AKT ，p-AKT ，mTOR and p-mTOR were detected by western blot assay.【Results】B16- F10 melanoma xenograft model showed that anti- PD- L1 antibody group had no obvious antitumor effect ，while both cabozantinib group and combination group produced significant antitumor effect，and the combination group had more obvious antitumor effect compared to cabozantinib group（P=0.001 5）. B16- F10 cells were treated with different drugs in vitro，and the apoptosis rate of the combination group was significantly higher than that of cabozantinib group at 24 h and 48 h，respectively（24 h:P=0.003 5；48 h:P=0.002 9）. Western blot assay showed that the combination group and cabozantinib group had no significant effect on the protein expression of AKT and mTOR，but both could reduce their phosphorylation levels，and the combination group was more remarkable. 【Conclusion】Cabozantinib in combined with anti-PD-L1 antibody had synergistic anti-tumor effect，which might be achieved by promoting B16-F10 cells apoptosis and inhibiting of AKT/mTOR pathway.