Development of a core outcome set of clinical research on the integration of traditional Chinese and Western medicine for spinal metastases: a study protocol.

BACKGROUND: In recent years, the incidence of spinal metastasis (SM) has been increasing steadily. In response to this serious public health problem, researchers have made progress by using the integration of traditional Chinese and Western medicine. However, considerable heterogeneity in the definition and measurement of outcomes across clinical research studies, along with the lack of uniform measurement standards for study data, makes it difficult for researchers to compare different treatments. Therefore, it is crucial to accurately evaluate clinical research on the integration of traditional Chinese and Western medicine for SM. METHODS: This study protocol outlines a comprehensive research programme based on the Core Outcome Set Standards Protocol Items. The study consists of four phases: a literature review, semistructured interviews, a two-round modified Delphi survey, a consensus meeting. Phase 1 involves a comprehensive literature review to extract outcomes used in current clinical studies of integrated traditional Chinese and Western medicine or Western medicine for the treatment of SM. A semistructured interview format will be used to survey patients and caregivers in phase 2 to collect suggestions from the patient perspective. Phase 3 involves a two-round modified Delphi survey to complete a prioritisation evaluation of outcomes to generate a candidate list for core outcome set (COS). Finally, phase 4 involves a face-to-face consensus meeting to review and establish the COS. ETHICS AND DISSEMINATION: Conducted in response to the current dilemma of SM, the study was endorsed by the Spine Oncology Group of the Orthopaedic Surgeons Branch of the Chinese Physicians' Association. It will be developed and reported through a rigorous process, with the results of the study to be published in a peer-reviewed journal.Registration: COMET Registry: COMET 2938; https://www.comet-initiative.org/Studies/Details/2938.

SENP2-NDR2-p21 axis modulates lung cancer cell growth.

Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G1/S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2-NDR2-p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment.

A critical appraisal of clinical practice guidelines on surgical treatments for spinal metastasis.

PURPOSE: As an important treatment for spinal metastasis, surgery has strict applicable conditions. Although various organizations have formulated different guidelines on surgical treatment for spinal metastasis (SM), there are certain differences in the content, standardization and quality of the guidelines and it is necessary to make a critical appraisal of them. We aim to systematically review and appraise the current guidelines on surgical treatments of SM and summarize the related recommendations with the quality evaluation of supporting evidence, as to provide a reference for the standardization of surgical treatment plans, and help clinical front-line medical workers can make safe and effective clinical decisions faster. METHODS: We searched Pubmed, Web of Science, and Embase for three major databases and online guideline databases. According to certain inclusion and exclusion criteria, the latest guidelines on the surgical treatment of SM were sorted out. AGREE II was used to evaluated the guideline's quality, and we extracted and compared the recommended treatment content of each guideline with evaluating by the evidence-grading scale. RESULTS: Eight guidelines from 2013 to 2019 were included. Seven guidelines are comprehensive guidelines and one related to the reconstructive surgery of SM. Five guidelines were evaluated as "recommended," and three guidelines were evaluated as "recommended with modifications." Regarding the indications of surgery with SM, four guidelines, seven guidelines, seven guidelines, three guidelines and three guidelines recommended surgical treatment for patients with SM with intractable pain, mechanical instability, metastatic epidural spinal cord compression (MESCC), recurrent spinal metastasis (RSM), and survival predication, respectively. Regarding the surgical strategies, three guidelines recommended minimally invasive therapy but had strict indications. Six guidelines and five guidelines recommend palliative surgery and with receiving radiation therapy, respectively. For the aggressive surgery, only one guideline recommended to apply to patients in good general conditions who has isolated symptomatic SM. Regarding the surgical reconstructions, one guideline didn't recommend iliac bone graft and three guidelines recommended PMMA bone cement. CONCLUSION: Most of the guidelines do not provide clear criteria for surgical application and provide more of a basic framework. The level of evidence for these surgical recommendations ranges from LOE B to D, and almost all guidelines recommend vertebroplasty and kyphoplasty, but for palliative and more aggressive surgery, which recommended to personalize specific surgical strategies with multidisciplinary collaboration.

Etoposide-induced SENP8 confers a feed-back drug resistance on acute lymphoblastic leukemia cells.

Chemotherapy is the most common treatment for acute lymphoblastic leukemia (ALL). However, many ALL patients eventually develop relapse and treating relapsed ALL has always been challenging. Therefore, exploring the resistance mechanism of chemotherapeutic drugs and proposing feasible intervention strategies are of great significance for ALL treatment. Here, we show that SENP8, whose coding protein is an important deNEDDylase targeting the substrate for deNEDDylation, is highly expressed in relapsed ALL specimens. Interestingly, overexpressing SENP8 specifically reduces the chemosensitivity of ALL cells to etoposide (VP-16) and significantly alleviates the proapoptotic effect of VP-16 on ALL cells. By contrast, NEDDylation inhibition reduces the chemosensitivity of ALL cells to VP-16. Furthermore, VP-16 induces SENP8 accumulation and the instability of MDM2 as well as the stabilization of p53 in ALL cells, and SENP8 knockdown can sensitize ALL cells to VP-16. Our study reveals a novel function of SENP8 in ALL and that VP-16-induced SENP8 confers a feed-back drug resistance on ALL cells, suggesting a possibility of overcoming the chemotherapeutic resistance to VP-16 via targeting SENP8.

Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review.

PURPOSE: Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, the authors aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM. METHODS: This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). 'Best evidence synthesis' was performed using COSMIN outcomes and the quality of findings. RESULT: Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, the Brief Pain Inventory (BPI) had the best methodological quality. CONCLUSIONS: Owing to the limitations of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies are needed to explore the evidence before a confirmatory decision is made.

Antileukemic effects of topoisomerase I inhibitors mediated by de-SUMOylase SENP1.

SUMO-specific proteases (SENPs) play pivotal roles in maintaining the balance of SUMOylation/de-SUMOylation and in SUMO recycling. Deregulation of SENPs leads to cellular dysfunction and corresponding diseases. As a key member of the SENP family, SENP1 is highly correlated with various cancers. However, the potential role of SENP1 in leukemia, especially in acute lymphoblastic leukemia (ALL), is not clear. This study shows that ALL cells knocking down SENP1 display compromised growth rather than significant alterations in chemosensitivity, although ALL relapse samples have a relatively higher expression of SENP1 than the paired diagnosis samples. Camptothecin derivatives 7-ethylcamptothecin (7E-CPT, a monomer compound) and topotecan (TPT, an approved clinical drug) induce specific SENP1 reduction and severe apoptosis of ALL cells, showing strong anticancer effects against ALL. Conversely, SENP1 could attenuate this inhibitory effect by targeting DNA topoisomerase I (TOP1) for de-SUMOylation, indicating that specific reduction in SENP1 induced by 7E-CPT and/or topotecan inhibits the proliferation of ALL cells.

Global Trends of the Research on Ossification of Posterior Longitudinal Ligament in Thoracic Spine: A Bibliometric and Visualization Study.

OBJECTIVE: Thoracic ossification of the posterior longitudinal ligament (TOPLL) is a rare but intractable disease, and is the second leading cause of thoracic myelopathy. This study aimed to illustrate the overall knowledge structure and development trends of TOPLL, using a bibliometric analysis and newly developed visualization tools. METHODS: Research data sets were acquired from the Web of Science. The literature search was also limited to articles that were published until October 30, 2021. VOS viewer and Citespace software was provided to analyze the data and generate visualization knowledge maps. Annual trend of publications, distribution, H-Index status, co-authorship status, and research hotspots were analyzed. RESULTS: A total of 206 publications met the requirement. Japan published most papers (92), both total citations (1574) and H-index (24) ranked first of all the countries. The most productive organization was Peking University (22). The most productive author was Yamazaki M (18). The most productive journal was Spine (33). Diagnosis and treatment on the accuracy of surgical segments, prognosis of patients, and gene research were the research hotspots in the recent years. CONCLUSIONS: The study showed an upward trend with a stable rise in recent years. Japan is country with the highest productivity, not only in quality, but also in quantity. Peking University and Spine have been the largest contributors. Indeed, this study provides great insights to the growth and development of TOPLL. Moreover, it will contribute to the growth of the international frontier.

Top 50 Most Cited Articles on Thoracic Ossification of Posterior Longitudinal Ligament.

Study Design: Bibliometric analysis. Objective: Over the last several decades, the field of thoracic ossification of the posterior longitudinal ligament (T-OPLL) has evolved unprecedentedly, and the literature on T-OPLL has increased significantly. The purpose of this study is to identify and review the top 50 most cited publications related to T-OPLL. Methods: The most frequently cited 50 articles in this field until 30 October 2021 were identified by searching Web of Science. We ranked the articles based on the citation number. Through the bibliometric method, we evaluated the following information: article title, first author, year of publication, journal of publication, total number of citations, country, and study topic. Results: The number of citations of included studies ranged from 20 to 108, with a mean number of 45.4. The journal Spine published most articles (20), followed by Spinal Cord (5), and European Spine (5). All of these articles were contributed by 38 first authors, Yamazaki (4), Fujimura (3), and Aizawa (3) who published more than 2 articles. In the respect of productive countries, Japan (39) contributed most papers. Tomita contributed the most cited article in 1990 on Spine, which was the first-ever report of circumferential decompression for thoracic myelopathy due to T-OPLL. Conclusion: The top 50 influential articles on T-OPLL were identified and analyzed in this study. It will undoubtedly provide a comprehensive and detailed basis for the orthopedic and neurosurgery physicians to make a clinical decision and assimilate the research focus of spine surgery.

Acupuncture for insomnia after ischemic stroke: an assessor-participant blinded, randomized controlled trial.

BACKGROUND: To date, there has been little focus on research into acupuncture for insomnia after ischemic stroke. Insomnia is one of the most common sequelae after ischemic stroke, and it is the most unrecognized modifiable risk factor. OBJECTIVE: To evaluate the efficacy and safety of acupuncture for insomnia after ischemic stroke. METHODS: In this assessor-participant blinded, randomized, controlled trial, 144 ischemic stroke patients with insomnia meeting Diagnostic and Statistical Manual of Mental Disorders (fifth edition, DSM-5) criteria were assigned to verum or sham acupuncture treatment (n = 72 per group) for three sessions per week over 4 weeks. The outcomes were the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), stroke-specific quality of life (SSQoL), and Hospital Anxiety and Depression Scale (HADS) scores. Multiple objective sleep variables were recorded using actigraphy. Assessment was conducted at baseline, and thereafter once biweekly for the 4-week treatment and at 4 weeks of follow-up. RESULTS: The verum acupuncture group had significantly greater improvements than the sham acupuncture group in sleep quality from 2 weeks into treatment throughout the follow-up, indicated by ISI scores and actigraphic variable SE (sleep efficiency). This greater improvement was also observed in the PSQI after 4 weeks of treatment throughout follow-up, as well as actigraphic variable TST (total sleep time), SSQoL and HADS scores at the end of treatment, and SSQoL and depression scores at follow-up. There was no significant difference between groups in the actigraphic variable SA (sleep awakenings). Adverse events were mild in severity, and their incidence was not significantly different between the two groups. CONCLUSION: Acupuncture appears to be efficacious, in terms of improving insomnia, related quality of life, and affective symptoms, for patients with ischemic stroke. TRIAL REGISTRATION NUMBER: ChiCTR-IIC-16008382 (Chinese Clinical Trial Registry).

Global and Current Research Trends of Unilateral Biportal Endoscopy/Biportal Endoscopic Spinal Surgery in the Treatment of Lumbar Degenerative Diseases: A Bibliometric and Visualization Study.

The study aimed to make a bibliometric analysis of the current research situation in unilateral biportal endoscopy/biportal endoscopic spinal surgery (UBE/BESS). Research data sets were acquired from the Web of Science database. The study chosed "biportal endoscopic spinal surgery" OR "two portal endoscopic spinal surgery" OR "percutaneous biportal endoscopic decompression" OR "unilateral biportal endoscopy" OR "irrigation endoscopic discectomy" as the search terms. The literature search was limited to articles published before March 5, 2021. We only included original articles and reviews. VOS viewer and Citespace software were used to analyze the data and generate visualization knowledge maps. Annual trend of publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed. A total of 74 publications met the requirement. The sum number of citations was 31,204, in which 19,336 were no self-citations. The average citation of all the papers was 21.84 times. The H-index of all the publications was 85. South Korea's total number of articles was far higher than that of other countries and regions (61, 82.4%), followed by United Arab Emirates, Egypt, and Peoples Republic of China (three, ranking second, accounting for 12.2% of the total). For the most productive authors, Choi ranked first with 21 articles, Kim ranked second with 16 articles, and Heo ranked third with 12 articles. The journal with the greatest number of publications was World Neurosurgery, with a total of 18 (39.1%) papers. Clinics in Orthopedic Surgery ranked second with six (13.0%) papers. In third place, there were fix articles published by Asian Spine Journal and Neurospine, accounting for 21.8% of the total articles. These top three journals accounted for 73.9% of all the papers. Spondylolisthesis and endoscopic decompression were the research hotspots in recent years. The number of publications has showed an upward trend with a stable rise in recent years. South Korea is the country with the highest productivity, not only in quality, but also in quantity. Barun Hosp and Leon Wiltse Mem Hosphave published most articles. Choi is the most productive author. World Neurosurgery is the most productive journal. Spondylolisthesis and endoscopic decompression are the research hotspots in recent years. Indeed, this study provides new insight into the growth and development of UBE/BESS.