Circadian rhythm(CR)is an intrinsic biological clock mechanism within organisms that regulates physiological and biochemical processes, enabling synchronization with periodic fluctuations in the external environment. This rhythmicity not only influences the sleep-wake cycle but also encompasses various physiological functions, including metabolism, hormone secretion, cell proliferation, and immune responses. Age-related macular degeneration(ARMD), a prevalent retinal disease, has been significantly associated with disruptions in CR. ARMD is among the leading causes of vision loss in the elderly, with a complex pathogenesis involving multiple factors such as genetics, environmental influences, and lifestyle choices. This article will focus on the molecular mechanisms linking CR and ARMD, analyzing how disruptions in CR affect the physiological state and metabolic processes of retinal cells, ultimately contributing to the onset and progression of ARMD. Additionally, this article will elucidate the interactions effects of CR on ARMD in relation to oxidative stress, regulation of Aβ, inflammatory pathways, and mitochondrial homeostasis. By deepening our understanding of the relationship between CR and ARMD, we aim to provide new insights and directions for future clinical interventions and treatments.

The pathological changes of myocardial infarction （MI） are mainly characterized by progressive myocardial ischemic necrosis， decline in cardiac diastolic function， thinning of the ventricular wall， and enlargement of the ventricles. The clinical manifestations include myocardial ischemia， heart failure， arrhythmia， shock， and even sudden cardiac death， rendering MI one of the most perilous cardiovascular diseases. Currently， the clinical treatment for MI primarily involves interventional procedures and drug therapy. However， due to their significant side effects and high complication rates associated with these treatments， they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand， traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB （NF-κB）， adenosine 5̒-monophosphate-activated protein kinase （AMPK）， transforming growth factor-β （TGF-β）/Smads， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions， traditional Chinese medicine can enhance MI management by inhibiting apoptosis， providing anti-inflammatory properties， alleviating oxidative stress levels， and resisting myocardial ischemia. Due to its notable efficacy and favorable safety， it has become an area of focus in clinical practice.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

[Objective] To investigate the infection and characteristics of hepatitis E virus among blood donors in Hangzhou. [Methods] A total of 5 075 blood samples of blood donors from Zhejiang Provincial Blood Center from September to November 2023 were collected, including 5 037 samples with normal ALT and 38 samples with elevated ALT (>50 U/L). Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HEV IgM, anti-HEV IgG and HEV-Ag. The Fisher test and Chi-square test were used to evaluate the difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT. The distribution characteristics of HEV screening in blood donors were analyzed. Univariate and multivariate logistic regression were used to analyze the susceptibility factors of anti-HEV IgM and anti-HEV IgG seropositivity, and the anti-HEV IgM-reactive blood donors were followed up by telephone. [Results] The reactivity rates of anti-HEV IgM, anti-HEV IgG and HEV-Ag in 5 075 blood samples were 0.45%, 22.98% and 0%, respectively. There was no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT (P>0.05), and the results of univariate and multivariate logistic regression analysis showed that age was a risk factor for anti-HEV IgM and anti-HEV IgG reactivity in blood donors (P<0.05), while no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among blood donors was noticed in gender, occupation and education level (P>0.05). [Conclusion] There is a potential risk of transfusion-transmitted HEV (TT-HEV) in Hangzhou, and a cost-effective HEV screening strategy needs to be established to continue regular HEV surveillance in Hangzhou to assess the risk of infection.

Yin-yang, visceral manifestation, and ti-yong theories are the core theories of traditional Chinese medicine (TCM) and play a crucial role in its formation and development. With the continuous evolution of Chinese philosophy, TCM philosophy and theories have undergone significant influence, resulting in differing interpretations of the visceral manifestation of liver and mingmen across various historical periods by different medical practitioners. This paper focuses on the different understandings of the position of liver and mingmen, combining relevant philosophical images and TCM anatomical illustrations to deeply explore ancient medical theorists′ concepts regarding the four spatial directions of left, right, up, and down. The research reveals that ancient medical theorists′ conceptualization of spatial theory transitioned from an initial circular motion to a vertical movement, with the focus shifting from the upper part to the lower part. The primary reasons for these differences and changes could be explained by the varying emphasis on the ti-yong theory and differing focal points within the yin-yang theory. This study systematically examines the evolution of visceral manifestation theories related to liver and mingmen, highlights the shifts in physicians′ perspectives on spatial theory, and analyzes the influence of the ti-yong theory and yin-yang theory on these changes. The findings aim to provide a theoretical guide for advancing research and clinical application of spatial theory in TCM, thereby fostering the integration of TCM philosophy with medical theory.

Guided by the theory of turbid pathogen disturbing clarity， this paper holds that the pathogenesis of otolith disorders involves the failure of clear yang to ascend and the internal generation of phlegm-turbidity as the initiating factors. The clinical manifestations are characterized by the intermingling of phlegm and fluid， as well as the disturbance between turbid and clear substances， while the root lies in spleen-kidney deficiency and depletion of primordial qi. Treatment strategies are formulated according to the different stages of the disease： in the acute phase， therapy focuses on warming and resolving phlegm-fluid retention， using a modified combination of Linggui Zhugan Decoction （苓桂术甘汤） and Zexie Decoction （泽泻汤）； in the residual phase， the approach shifts to tonifying qi and uplifting clear yang， with a modified combination of Shengxian Decoction （升陷汤） and Shengmai Power （生脉散）； in the consolidation phase， therapy aims to tonify the kidney and replenish essence， employing a modified version of Qiju Dihuang Pill （杞菊地黄丸）.

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1