Normal rhythmic myoelectrieal activity of the human stomach is 3 cpm, regulating gastric contractile activity. Dysrhythmia in gastric myoelectrieal activity is found to be associated with functional disorders of the stomach. Gastric dysrhythmias are classified into tachygastria (frequency higher than normal), bradygastria (frequency lower than normal) and arrhythmia (no rhythmic activity). Clinical significance of gastric dysrhythmias is discussed in this paper, outlined as follows: (a) What is normal gastric myoelectrieal activity and what is dysrhythmia? (b) How to detect gastric dysrhythmias? (c) Gastric dysrhythmias in clinical settings, (d) What may cause gastric dysrhythmias? (e) How to normalize gastric dysrhythmias?

Background: Although increasing clinical trials studying Shenfu injection (SFI) comprising panaxoside 0.8 mg/ml extracted from Panax ginseng C.A. Mey. and aconitine 0.1 mg/ml extracted from Aconitum carmichaeli Debeaux for elderly patients with severe pneumonia on biomarkers associated with COVID-19 progression are emerging, there is no evidence-based evaluation for the effect of SFI on elderly severe pneumonia.Objectives: To evaluate the effect of SFI on elderly patients with severe pneumonia providing hints for treating critical COVID-19, we conducted a systematic review and meta-analysis.Methods: Nine databases, namely, PubMed, EMBASE, Web of Science, Science Direct, Google Scholar, Wanfang, Chongqing VIP Database, CNKI, and SinoMed were used to search clinical trials reporting the effect of SFI as an adjuvant for elderly severe pneumonia on outcomes of interest. Primary outcomes were total effective rate, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mortality, and safety. Secondary outcomes were predictors associated with COVID-19 progression. Duplicated or irrelevant articles with unavailable data were excluded. Cochrane Collaboration’s tool was used to evaluate the risk of bias by two reviewers independently. All data were analyzed by Rev Man 5.4. Continuous variables were shown as weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence intervals (95% CI), whereas dichotomous data were calculated as the risk ratio (RR) with 95% CI.Results: We included 20 studies with 1, 909 participants, and the pooled data showed that compared with standard control, SFI could improve the total effective rate (RR = 1.25, 95% CI = 1.14–1.37, and n = 689), APACHE II score (WMD = −2.95, 95% CI = −3.35, −2.56, and n = 809), and predictors associated with COVID-19 progression (brain natriuretic peptide, creatine kinase, stroke volume, cardiac output, left ventricular ejection fraction, cardiac index, sE-selectin, von Willebrand factor, activated partial thromboplastin time, platelet counts, D-Dimer, procalcitonin, and WBC count). SFI may reduce mortality (RR = 0.52, 95% CI = 0.37–0.73, and n = 429) and safety concerns (RR = 0.29, 95% CI = 0.17–0.51, and n = 150) for elderly severe pneumonia.Conclusion: SFI as an adjuvant may improve the total effective rate, APACHE II score, gas exchange, and predictors associated with COVID-19 progression, reducing mortality and safety concerns for elderly patients with severe pneumonia.

Selective neuronal vulnerability is a hallmark of Alzheimer’s disease (AD), yet the molecular basis of resilience remains poorly understood. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex, precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing RORB , CUX2 , and EYA4 . Layer 4 neurons in association neocortex shared molecular signatures of resilience. Early-stage resilient neurons upregulated genes associated with synapse maintenance, synaptic plasticity, calcium homeostasis, and neuroprotection ( GRIN2A, RORA, NRXN1, NLGN1, NCAM2, FGF14, NRG3, NEGR1 , CSMD1) . We identified KCNIP4 , which encodes a voltage-gated potassium channel-interacting protein, as a key resilience factor consistently upregulated during early stages of AD pathology. AAV-mediated overexpression of Kcnip4 in male App ^SAA mice reduced the expression of activity-dependent genes Arc and c-Fos , suggesting compensatory mechanisms against neuronal hyperexcitability. Our dataset provides a resource for investigating mechanisms underlying resilience to neurodegeneration.

Intercellular communication in the central nervous system (CNS) is essential for maintaining neural function and coordinating responses to injury or disease. With recent advances in single-cell and spatial transcriptomics, a growing body of research has revealed that this communication is highly dynamic, shifting across states of health, aging, demyelination, and neurodegeneration. In this review, we synthesize the current findings on intercellular communication networks involving neurons, astrocytes, microglia, oligodendrocytes, and other glial populations in the CNS across four major states: healthy homeostasis, aging, demyelinating diseases, and Alzheimer’s disease (AD). We focus on how changes in intercellular communication contribute to the maintenance or disruption of CNS integrity and function. Mechanistic insights into these signaling networks have revealed new molecular targets and pathways that may be exploited for therapeutic intervention. By comparing the intercellular signaling mechanisms across different disease contexts, we underscore the importance of CNS crosstalk not only as a hallmark of disease progression, but also as a potential gateway for precision therapy.

Alzheimer's Disease (AD) is a neurodegenerative condition characterized by the accumulation and deposition of amyloid‐β (Aβ) aggregates in the brain. Despite a wealth of research on the toxicity of Aβ and its role in synaptic damage, the mechanisms facilitating Aβ clearance are not yet fully understood. However, microglia, the primary immune cells of the central nervous system, are known to maintain homeostasis through the phagocytic clearance of protein aggregates and cellular debris. In this study, RNA sequencing analysis and live cell functional screens are employed to uncover microglial genetic modifiers related to AD. Lyzl4 is identified, which encodes a c‐type lysozyme‐like enzyme primarily localized to microglial lysosomes, as a gene significantly upregulated in AD microglia with aging and propose that Lyzl4 upregulation acts as a positive regulator of Aβ clearance. Furthermore, it is found that Lyzl4 overexpression boosts Aβ clearance both in vitro and in vivo, underscoring its potential for mitigating Aβ burden. These novel insights position Lyzl4 as a promising therapeutic target for Alzheimer's disease, paving the way for further exploration into potential AD treatments.

Degenerative orthopedic diseases, traditionally viewed as inevitable "wear-and-tear" processes, are now being reimagined as dynamic failures of tissue homeostasis orchestrated by a complex interplay of chronic inflammation and metabolic exhaustion. Over the past decade, the field of stem cell therapy, specifically involving mesenchymal stromal/stem cells (MSCs) and induced pluripotent stem cells (iPSCs) has transitioned from a simplistic "cell replacement" model to a sophisticated "niche reprogramming" paradigm. This Research Topic curates four pivotal contributions that integrate global clinical landscapes, bibliometric trajectories, and granular mechanistic insights to define the next generation of regenerative orthopedics.A successful transition from bench to bedside requires resolving the structural paradoxes within clinical development and scientific focus. Li et al. 1 provide an exhaustive mapping of 224 global clinical trials for osteoarthritis (OA), uncovering a "translational chasm" where the exponential expansion of early-phase trials stands in stark contrast to the scarcity of Phase III successes. This discrepancy reveals an urgent need for robust potency assays and precision-stratified patient cohorts to manage clinical heterogeneity.Parallel to these clinical shifts, the bibliometric mapping by Ai et al. 2 uncovers a decisive transition in the scientific center of gravity, where the focus has evolved from traditional structural scaffolds toward exosome-mediated biological signaling. This trajectory reflects a strategic industry-wide push toward cell-free paradigms, which circumvent the logistical and safety constraints of live-cell transplantation by utilizing stem cell-derived secretomes. Such systems offer superior scalability and refined immunogenic profiles, effectively redefining the standards for future regenerative products by prioritizing functional bio-signaling over mere structural replacement.Therapeutic efficacy in regenerative orthopedics is increasingly predicated on understanding the molecular cross-talk between therapeutic agents and their degenerate environment, particularly in complex systemic contexts. Xie et al. 3 provide a compelling case for cell-free intervention by elucidating how chronic hyperglycemia in Diabetic Osteoarthritis biophysically rewires the MSC secretome. Their review underscores that MSC-derived exosomes (MSC-Exos) serve as critical mediators that can be engineered to counteract the NLRP3-mediated "pyroptotic" environment, emphasizing that future strategies must be comorbidity-aware to override systemic metabolic interference.In a complementary yet fascinating mechanistic contrast, Junuzović et al. 4 shift the focus back to the intricate physical interactions of cell-based therapies. By challenging the conventional paracrine-only dogma, they highlight the transformative role of mitochondrial transfer through tunneling nanotubes (TNTs). This suggests a dual-track regenerative logic: while cell-free exosomes offer a scalable, "off-the-shelf" approach to signaling modulation as discussed by Xie et al., the direct donation of functional organelles by live MSCs restores the bioenergetic integrity of exhausted chondrocytes at a foundational level. Together, these insights demonstrate that regenerating a hostile niche involves a sophisticated interplay between cellfree systemic signaling reprogramming and live-cell direct metabolic rescue, providing a multidimensional toolkit for personalized regenerative medicine.The findings within this collection suggest that the "therapeutic ceiling" of regenerative orthopedics will be broken by the integration of bio-engineering and RNA biology. The development of injectable, responsive hydrogels and the molecular "loading" of specific microRNAs into extracellular vesicles are key strategies. These innovations aim to ensure that the regenerative signal persists long enough to override the proteolytic and pro-inflammatory environment characteristic of degenerative joints.As this Research Topic concludes, it is imperative to situate orthopedic regeneration within the broader framework of Geroscience, which posits that chronic degenerative diseases share a common set of biological drivers. The pathophysiology of musculoskeletal decay-traditionally viewed in isolation-is increasingly recognized as part of a systemic "geropathy" that mirrors the decline of the central nervous system (CNS) 5 .The "inflammaging" profile observed in the osteoarthritic joint-characterized by the accumulation of senescence-associated secretory phenotypes (SASP) [6][7][8] and the failure of proteostatic surveillance-finds a profound parallel in the neurodegenerative milieu of Alzheimer's and Parkinson's diseases 9,10 . Both the articular chondrocyte and the post-mitotic neuron exist within highly specialized niches where the loss of cellular "tiling" and homeostatic polarization (e.g., the M1/M2 macrophage-microglia spectrum) leads to irreversible tissue loss 11 .The emerging concept of the "Bone-Brain Axis" suggests a deep, bidirectional metabolic coupling between skeletal health and cognitive integrity 12,13 . Osteokines and bone-derived extracellular vesicles (EVs) are no longer viewed as localized messengers but as systemic rheostats of inflammation 14 . The engineered stem cell strategies discussed in this collectiondesigned to reprogram the joint microenvironment-hold transformative potential for neurobiology 15 . Specifically, the potential for MSC-derived EVs to cross the blood-brain barrier and modulate microglial proteostasis provides a unique opportunity to apply orthopedic breakthroughs to neuro-regeneration [16][17][18] .Future research must pivot from organ-specific inquiries to a unified regenerative logic. Can the "mitochondrial rescue" mechanisms observed in mesenchymal-chondrocyte interactions be harnessed to restore bioenergetics in the aging neuro-glial unit? Could the anti-senescence RNAs refined for...