Modulations of resting-static functional connectivity on insular by electroacupuncture in subjective tinnitus

ObjectiveTo explore the modulations of electroacupuncture in subjective tinnitus (ST) by comparing the difference of functional connectivity (FC) in ST patients and healthy volunteers between the insular (INS) and the whole brain region.MethodsA total of 34 ST patients were selected into electroacupuncture group (EG) and 34 age- and sex-matched normal subjects were recruited into control group (CG). The EG received acupuncture at SI19 (Tinggong), GB11 (Touqiaoyin), TE17 (Yifeng), GV20 (Baihui), GV15 (Yamen), GV14 (Dazhui), SJ13 (Zhongzhu), among which the points of SI19 and GB11 were connected to the electroacupuncture instrument with the density wave of 2/50 Hz, and 3 treatments per week for 10 sessions in total. The severity of tinnitus was evaluated by Tinnitus Handicap Inventory (THI), the hearing status was recorded using pure tone audiometry, and resting-state functional magnetic resonance imaging (rs-fMRI) was performed on the brain before and after treatment, the CG received no intervention yet only rs-fMRI data were collected.ResultsWith the electroacupuncture treatment, the total THI score, average air conduction threshold of patients of EG were significantly lower than before (p < 0.01), and the total effective rate was 88.24%. Compared with CG, FC of ST patients between INS and left superior temporal gyrus and right hippocampal significantly decreased before treatment, while FC of ST patients between INS and right superior frontal gyrus, left middle frontal gyrus and right anterior cuneus significantly decreased after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of ST patients between the INS and right middle frontal gyrus, left superior frontal gyrus and right paracentral lobule showed a significant decrease after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). In addition, THI score in EG was negatively correlated with the reduction of FC value in INS-left superior frontal gyrus before treatment (r = −0.41, p = 0.017). Therefore, this study suggests that abnormal FC of INS may be one of the significant central mechanisms of ST patients and can be modulated by electroacupuncture.DiscussionElectroacupuncture treatment can effectively reduce or eliminate tinnitus symptoms in ST patients and improve the hearing by decreasing FC between the INS and the frontal and temporal brain regions

The Path Constitution of Platform Evolution: An Organizational Momentum View

Although the evolutionary pathways are critical to the success of platforms, extant literature has provided little insight into the dynamic processes of the platform evolution, let alone how platforms constitute the evolutionary pathways over time. Against this backdrop, this study examines the evolutionary path constitution of platforms by adopting an organizational momentum lens. Through an exploratory case study of Pinduoduo, it provides evidence of path dependence under the network effects and of path creation resulting from the deliberate actions conducted by the platform firms. Moreover, this study identifies three platform strategies to manage its momentum to facilitate platform evolution and sustainability. Furthermore, this study develops a holistic framework to explain the interactions between platform momentum and path constitution by considering the outcomes of these strategies. The findings and developed framework shed novel light on the path constitution of platform evolution and provide new insight into the sustainability of the platform firms and platform-based markets by leveraging momentum thinking

The Path Constitution of Platform Evolution: An Organizational Momentum View

Although the evolutionary pathways are critical to the success of platforms, extant literature has provided little insight into the dynamic processes of the platform evolution, let alone how platforms constitute the evolutionary pathways over time. Against this backdrop, this study examines the evolutionary path constitution of platforms by adopting an organizational momentum lens. Through an exploratory case study of Pinduoduo, it provides evidence of path dependence under the network effects and of path creation resulting from the deliberate actions conducted by the platform firms. Moreover, this study identifies three platform strategies to manage its momentum to facilitate platform evolution and sustainability. Furthermore, this study develops a holistic framework to explain the interactions between platform momentum and path constitution by considering the outcomes of these strategies. The findings and developed framework shed novel light on the path constitution of platform evolution and provide new insight into the sustainability of the platform firms and platform-based markets by leveraging momentum thinking

Combining IL-2-based immunotherapy with commensal probiotics produces enhanced antitumor immune response and tumor clearance

Background Interleukin-2 (IL-2) serves as a pioneer of immunotherapeutic agent in cancer treatment. However, there is a considerable proportion of patients who cannot benefit from this therapy due to the limited clinical responses and dose-limiting toxicities. Mounting evidence indicates that commensal microbiota shapes the outcome of cancer immunotherapies. In this study, we aim to investigate the enhancing effect of Akkermansia muciniphila (AKK), a beneficial commensal microbe receiving considerable attentions, on the antitumor efficacy of IL-2 and explore the underlying molecular mechanism.Methods Colorectal carcinoma patient-derived tumor tissues were used to evaluate the therapeutic efficacy of combination treatment. AKK was orally delivered to B16F10 and CT26 tumor-bearing mice along with systemic IL-2 treatment. Flow cytometry was carried out to analyze the tumor immune microenvironment. The molecular mechanism of the enhanced therapeutic efficacy was explored by RNA-seq and then verified in tumor-bearing mice.Results Combined treatment with IL-2 and AKK showed a stronger antitumor efficacy in colorectal cancer patient-derived tumor tissues. Meanwhile, the therapeutic outcome of IL-2 was significantly potentiated by oral administration of AKK in subcutaneous melanoma and colorectal tumor-bearing mice, resulting from the strengthened antitumor immune surveillance. Mechanistically, the antitumor immune response elicited by AKK was partially mediated by Amuc, derived from the outer membrane protein of AKK, through activating toll-like receptor 2 (TLR2) signaling pathway. Besides, oral supplementation with AKK protected gut barrier function and maintained mucosal homeostasis under systemic IL-2 treatment.Conclusion These findings propose that IL-2 combined with AKK is a novel therapeutic strategy with prospecting application for cancer treatment in clinical practice

Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint.