The distribution of the common acupoints of acupuncture-moxibustion for gastrointestinal diseases conforms to the rule of the segmental homology of somatic afferent nerve-visceral nerve circuit at the spinal cord level. Acupuncture-moxibustion regulates the gastrointestinal function through the nerve-endocrine-immune system, and especially depending on the integrity of the structure and function of nervous system. The somatic afferent nerve-visceral nerve circuit plays an important role in the process of acupuncture and moxibustion for regulating the gastrointestinal function. There are three dimensions. ① The somatic afferent nerve-visceral nerve circuit at the peripheral level, including the somatic afferent nerve-visceral afferent nerve circuit centered on the dorsal root ganglion, and the somatic afferent nerve-visceral efferent nerve circuit centered on the sympathetic ganglia; ② that at the spinal cord level; ③ that at the supra-spinal cord level, focusing on the various reflex circuits with the solitary nucleus involved. The somatic afferent nerve-visceral nerve circuit at the spinal level and inferior to it determines the segmental regulation of acupuncture-moxibustion in the gastrointestinal system, while that at the level superior to the spinal cord determines the supersegmental action of acupuncture-moxibustion in regulating the gastrointestinal system. The neurophysiological mechanism of acupuncture-moxibustion is multi-circuits and multi-targets in regulating gastrointestinal function.
Humans ; Moxibustion ; Acupuncture Therapy ; Acupuncture Points ; Gastrointestinal Tract/physiology* ; Animals ; Neurons, Afferent/physiology* ; Afferent Pathways/physiology*

In the era of big data, neuroimaging and algorithmic analyses have propelled brain science research and brain mapping. Acupuncture, widely recognized as an effective surface stimulation therapy, has demonstrated therapeutic efficacy for various brain conditions such as stroke and depression. However, the mechanisms linking acupuncture to brain function and its modulatory effects on brain activity require systematic exploration. Additionally, there is an urgent need to scientifically reinterpret traditional meridian theory and enhance its clinical applicability. Therefore, we propose the initiative of constructing a "brain mapping atlas of meridian, collateral and body surface stimulation" to explore the patterns linking the therapeutic effects of stimulating the twelve meridians, eight extraordinary vessels, divergent channels, collateral channels, sinew channels, and skin regions to brain function. This initiative aims to provide a scientific interpretation of traditional Chinese medicine meridian theory and enhance its practical applicability. This paper begins by reviewing the current state of brain mapping. It then summarizes existing research on the relationship between acupuncture and the brain, highlighting the necessity of constructing this atlas. The paper further analyzes the methodologies and technical challenges involved. Finally, the potential applications of the brain mapping atlas of meridian, collateral and body surface stimulation, and its main significance in advancing traditional meridian theory to keep pace with the times are prospected.
Humans ; Acupuncture Therapy ; Meridians ; Big Data ; Brain/physiology* ; Brain Mapping

The correlation between meridians and zangfu organs is one of the core contents of the theory of zangfu organs and meridians, which has significant research value and clinical application potential. In this paper, the research literature on correlation between meridians and zangfu organs in the past five years is sorted out and summarized, and it is found that more clinical application basis is added in meridian-diagnosis, and a new situation of high-quality evidence-based medicine is opened in the aspect of meridian-treatment. In terms of internal connection and biological mechanism, the neurobiological characteristics and regulatory mechanism represented by "heart meridian-heart" are illustrated. The research model of the relationship between the meridians-zangfu organs and the brain, which combines the functional connection of the brain network in clinic and the basic neural circuit mechanism under the premise of the "effect law", is clearly proposed.
Meridians ; Humans ; Brain/physiology*

OBJECTIVE: To observe the clinical efficacy of Tongtiao acupuncture-moxibustion method for long COVID-19 olfactory dysfunction. METHODS: A total of 28 patients with long COVID-19 olfactory dysfunction were selected and treated with Tongtiao acupuncture-moxibustion therapy (regulating orifices, invigorating the brain, and regulating qi and blood). Acupoints included Yintang (GV24⁺), Baihui (GV20), Fengfu (GV16), Qihai (CV6) and bilateral Yingxiang (LI20), Fengchi (GB20), Xuehai (SP10), Zusanli (ST36). Deep needling to the periosteum of the nasal bone was performed at Yintang (EX-HN3), with warming needle moxibustion applied. Each treatment lasted 40 min, administered once daily for 6 days per week, followed by a 1-day rest, over 4 consecutive weeks. T&T olfactory test scores, TCM symptom scores, serum cortisol levels, Hamilton depression scale (HAMD) scores, and Hamilton anxiety scale (HAMA) scores were compared before and after treatment. Clinical effect was evaluated based on T&T olfactory test grading. RESULTS: Compared before treatment, the T&T olfactory test scores, each TCM symptom scores, HAMD scores, and HAMA scores were decreased after treatment (P<0.01, P<0.05), while serum cortisol level was increased (P<0.01). The total effective rate was 96.4% (27/28). CONCLUSION Tongtiao acupuncture method could effectively alleviate symptoms of long COVID-19 olfactory dysfunction, increase serum cortisol level, and relieve anxiety and depressive symptoms.
Humans ; Moxibustion ; Male ; Female ; COVID-19/therapy* ; Acupuncture Therapy ; Middle Aged ; Adult ; Acupuncture Points ; Olfaction Disorders/virology* ; Aged ; SARS-CoV-2/physiology* ; Treatment Outcome

Electroencephalography (EEG) and magnetic resonance imaging (MRI), as neuroimaging technologies, provided objective and visualized technical tools for analyzing the brain effect mechanisms of acupuncture and moxibustion from the perspectives of brain structure, function, metabolism, and hemodynamics. The advancement of artificial intelligence (AI) algorithms can compensate for issues such as the large and scattered nature of neuroimaging data, inconsistent quality, and high heterogeneity of image information. The integration of AI with neuroimaging can facilitate individualized, intelligent, and precise prediction of acupuncture and moxibustion effects, enable intelligent classification of differential acupuncture responses, and identify brain activation patterns. This paper focuses on EEG and MRI, analyzing how machine learning and deep learning optimize multimodal neuroimaging data and their applications in the study of acupuncture and moxibustion brain effects mechanisms. Furthermore, it highlights current research gaps and limitations to provide insights for future studies on acupuncture brain effects mechanisms.
Humans ; Acupuncture Therapy ; Brain/physiology* ; Moxibustion ; Neuroimaging/methods* ; Artificial Intelligence ; Magnetic Resonance Imaging ; Electroencephalography

INTRODUCTION: Odour recognition is influenced by culture. Odour identification tests need to be adapted to a population to accurately assess olfactory function. This study's objectives were to validate the Singapore version of the Sniffin' Sticks (SS-Sg) and a locally-developed odour recognition test (Scentsor) for Singapore. METHOD: This prospective study was performed in 3 otolaryngology outpatient clinics in 3 phases (1 May to 15 November 2024). Phase 1 was a survey evaluation of 93 odour descriptors to identify familiar odour descriptors to be used in the tests (n=414); Phase 2 evaluated and finalised SS-Sg and Scentsor to ensure test odours were recognised by ≥75% of healthy controls (n=130); and Phase 3 validated both tests on healthy controls (n=473) to obtain normative data, to determine test-retest reliability (n=50), and to assess the ability to distinguish patients with olfactory loss (n=67). RESULTS: In Phase 1, the unmodified SS blue and purple sets had 15/32 (46.9%) unfamiliar test odours and 25 unfamiliar distractors combined. In Phase 2, after modification, all odours in SS-Sg and Scentsor were correctly identified by ≥75% of controls. In Phase 3, normative data (age 21-83 years) was obtained. Both tests had good test-retest reliability (Pearson's correlation coefficient of 0.88 with<0.001 for SS-Sg; and at 0.90 with<0.001 for Scentsor). Both tests differentiated among normosmia, hyposmia and anosmia (SS-Sg scores: 12.6 [±2.4] versus [vs] 9.8 (±3.2) vs 6.0 [±2.3] respectively,<0.001; Scentsor scores: 14.3 [±1.8] vs 11.3 [±2.8] vs 5.8 [±3.4] respectively,<0.001). CONCLUSION SS-Sg and Scentsor have been validated to assess olfaction in Singapore.
Humans ; Singapore ; Male ; Female ; Odorants/analysis* ; Middle Aged ; Prospective Studies ; Olfaction Disorders/diagnosis* ; Adult ; Reproducibility of Results ; Aged ; Smell/physiology* ; Young Adult

BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.
Humans ; Hypotension/complications* ; Cognitive Dysfunction/etiology* ; Alzheimer Disease/epidemiology* ; Cerebrovascular Circulation/physiology* ; Cognition Disorders/etiology*

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans ; Acute Kidney Injury/metabolism* ; Lactic Acid/metabolism* ; Animals ; Glycolysis/physiology* ; Gluconeogenesis/physiology* ; Kidney/metabolism*