Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Objective: To analyze the epidemilogical and seasonal characteristics of foodborne Salmonella-associated diarrhea among children aged 0-6 years in Guizhou Province from 2016 to 2023, so as to provide a basis for the prevention and control of foodborne diseases. Methods: Data were extracted from the Foodborne Disease Survellance System for cases reported between January 1, 2016, and December 31, 2023. The incidence, seasonal characteristics, and peak periods were analyzed by the method of concentration and circular distribution. Results: A total of 6 434 cases of diarrhea in children aged 0-6 years were collected, and 455 cases of Salmonella were detected, with a positive detection rate of 7.07%. Salmonella typhimurium was the main serotype causing diarrhea (59.34%). The peak of the disease was from May 3 to September 30, with certain seasonal characteristics. The highest detection rate was found in children aged 1-3 years (8.66%). Among food types, the positive detection rates of Salmonella were relatively high in other foods (17.39%), fruits and their products (10.22%), infant and toddler foods (10.09%), and aquatic animals and their products (9.80%). The processing and packaging methods of food were mainly home-made (9.38%) and bulk food (7.54%). Conclusions The detection rate of Salmonella in children aged 0-6 years is high in Guizhou Province, with strong seasonal characteristics. The detection rates of other foods, fruits and their products, infant and toddler foods, and aquatic animals and their products are high. Enhanced pathogen surveillance for susceptible populations and high-risk foods, coupled with public health education during summer/autumn, is recommended.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
Mice ; Animals ; Mitogen-Activated Protein Kinase 14/metabolism* ; Wolfiporia ; Lipopolysaccharides/pharmacology* ; Sepsis/complications* ; Signal Transduction ; Inflammation/drug therapy* ; Oxygen Radioisotopes

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Objective:To explore the assessment value of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and tumor markers in assessing the curative effect of neoadjuvant chemotherapy for breast cancer.Methods:A total of 75 patients with breast cancer who received neoadjuvant chemotherapy combined with surgical intervention in Jining No.1 People's Hospital from May 2019 to May 2022 were selected,and they were divided into effective group(54 cases)and ineffective group(21 cases)according to the Response Evaluation Criteria In Solid Tumour(RECIST).The Ve,Kep and Ktrans of DCE-MRI quantitative parameters and CEA,CA125 and CA15-3 levels of tumor markers between two groups were compared before and after chemotherapy,and the receiver operating characteristics(ROC)curve was adopted to analyze the predictive efficiency of each diagnostic method.Results:After chemotherapy,the differences of the Ve,Kep and Ktrans of quantitative parameters between the two groups were significant(t=7.237,51.695,16.879,P<0.05),respectively.The differences of the CEA,CA125 and CA15-3 of tumor markers between two groups were significant(t=44.201,6.736,6.885,P<0.05),respectively.The AUC value of combined prediction of 6 indicators included Ve,Kep,Ktrans,CEA,CA125 and CA15-3 was 0.979 in predicting the curative effect of neoadjuvant chemotherapy for breast cancer,which was significantly higher than the AUC value of each alone indicator,and the differences of them were statistically significant(Z=2.993,2.679,2.510,2.731,3.215,3.071,P<0.05),respectively.Conclusion:The combination of tumor markers and DCE-MRI quantitative parameters can better predict the curative effect of neoadjuvant chemotherapy for breast cancer,which can indirectly assess the prognosis.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.