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2025 Volume 47 Issue 4  Published: 2025-02-28
    Expert Review
  • Mindian LI , Jianxin ZHANG
    doi: 10.16016/j.2097-0927.202501018

    Metabolic diseases, including obesity and diabetes, etc., are a spectrum of life-threatening diseases, in which metabolic dysfunction is a hallmark. It is in urgent need of new insights for the prevention and treatment of the diseases. Circadian rhythm is fundamental in health and wellbeing. Research on circadian rhythm has shed light on metabolic homeostasis, thereby giving birth to a new direction, named circadian metabolism. Here, we summarize recent advances in circadian metabolism regarding organelle regulation, inter- and intra-organ crosstalk of circadian clocks, as well as molecular mechanisms of time-restricted eating, and propose circadian communication across the hierarchy of central and peripheral clocks as a key concept for understanding the temporal regulation of metabolism. The underlying mechanisms on circadian communication should shed light on precision medicine in a temporal resolution and provide guidelines on when to eat and when to exercise for the prevention of metabolic diseases.

  • Expert Review
  • Bo HU , Xuan TAN
    doi: 10.16016/j.2097-0927.202504093

    Memory refers to the physiological process in which the brain is able to keep the information obtained from both internal and external sources over an extended period of time. In the brain, neuronal ensembles distributed across multiple regions encode information about past scenes or events and form long-term memories, which then can guide individuals' behavior in similar scenes or events. Unless been consolidated, these newly-formed memories decay quickly. Sleep is a brain state with multiple physiological functions, including non-rapid eye movement sleep (NREM) and rapid eye movement (REM) sleep. Memory formation involves 3 processes: encoding, consolidation, and retrieval. Both reduced sleep time and fragmented sleep can lead to the impaired consolidation of various types of memory, indicating that one of the important physiological functions of sleep is beneficial for the memory consolidation. In this article, we summarizes the critical evidence that NREM sleep and REM sleep are involved in memory consolidation, and discuss how sleep promotes memory consolidation through the mechanisms such as ensemble reactivation and synaptic modification. Future researches may include further exploration on how sleep coordinates synaptic "down-scaling" with "up-scaling", how REM sleep complements with NREM sleep, the involvement of glial cells activity during sleep in memory consolidation, and whether and how brain regions controlling NREM and REM sleep directly participates in the regulation of memory consolidation.

  • Monographic Reports
  • Lei ZHANG , Minmin LU , Xiaolong ZHANG , Chao HE , Qin XIAO
    doi: 10.16016/j.2097-0927.202412132
    Objective

    To determine the effect of thalamic nucleus reuniens (RE) on sleep spindles and neuronal activity in the medial prefrontal cortex (mPFC) during non-rapid eye movement (NREM) sleep.

    Methods

    Thirteen wild-type C57BL/6 male mice (8~12 weeks old, weighing 22~28 g) were randomly divided into an experimental group (n=7) and a control group (n=6). Optogenetic inhibition combined with multi-channel recording technology was used to specifically inhibit RE projections to mPFC during NREM sleep with yellow light for 20 s, in a 5-min interval between 2 times of light stimuli. The types and distribution of neurons were identified based on the waveform width and firing frequency of neurons. The changes in spindle activity in the mPFC following inhibition, as well as in firing of interneurons and pyramidal neurons were analyzed.

    Results

    Morphological data confirmed that neural fibers originating from the RE densely projected to the mPFC, primarily distributed in the deep layers. In the experimental group, light stimulation significantly affected the spindle activity in the mPFC when compared with the period before light stimulation, mainly manifested as a decrease in spindle rate, central frequency, and peak-to-peak amplitude ( P<0.05). However, no impacts on spindle duration, number of cycles, symmetry, and power were observed. Meanwhile, there were no significant changes in the spindle activity of the control group. The proportion of interneurons in the mPFC area was 21.9%, while pyramidal neurons accounted for 78.1%. The firing rates of interneurons in the experimental group decreased significantly during light stimulation (P<0.05), whereas there was no significant change in the firing rates of pyramidal neurons. In addition, the firing activities of both interneurons and pyramidal neurons in the control group remained unaffected.

    Conclusion

    During NREM sleep, RE inputs may participate in the generation of sleep spindles network oscillations in the mPFC by activating interneurons.

  • Monographic Reports
  • Yue ZHAN , Rongrong LI , Jie ZHANG , Hongli LI
    doi: 10.16016/j.2097-0927.202501016
    Objective‍

    To investigate the effects of sleep deprivation on the firing activity of hippocampal parvalbumin-expressing interneuron (PV-IN) of mice during trace eyeblink conditioning (tEBC) training and during recovery sleep.

    Methods‍

    A total of 15 PV-Cre mice were randomly assigned into a sleep deprivation group (n=8) and a control group (n=7). After daily tEBC training, the sleep deprivation group experienced 1.5 h of sleep deprivation followed by 1.5 h of recovery sleep, and the control group mice were allowed to sleep freely, for 5 consecutive days. Multichannel recording and optogenetic techniques was applied to identify the hippocampal PV-IN in vivo.

    Results‍

    The sleep deprived mice failed to show significant increase in the incidence of conditioned eyeblink response (CR) across 5 training days (P>0.05). On training days 3~5, the CR incidence was significantly lower in the sleep deprived mice than the control mice (P<0.05). The enhancement of conditioned stimulus (CS)-evoked firing activity in hippocampal PV-INs during tEBC training was significantly lower in the sleep deprived mice when compared to the control mice (P<0.05). The sleep deprived mice obtained notably strengthened firing activity of hippocampal PV-INs peri sharp wave ripple events during recovery sleep period when compared with the pre-training sleep period (P<0.05), and the enhancement was remarkably greater than that in the control mice (P<0.05). Sleep deprivation had no obvious effects on the firing activity of hippocampal non PV-IN during either tEBC training or recovery sleep (P>0.05).

    Conclusion‍

    Sleep deprivation produces dual effects on the firing activities of hippocampal PV-INs during tEBC training and recovery sleep. These effects may be the cellular mechanisms of tEBC memory formation and consolidation disorders caused by sleep deprivation.

  • Monographic Reports
  • Yimeng WANG , Qing CHEN , Siwen LUO , Fuquan SHI , Mengchao HE , Shengfeng WANG , Qiaorui WEN , Yingzhong DAI , Hao QU , Jia CAO
    doi: 10.16016/j.2097-0927.202410006
    Objective

    To investigate the impact of sleep modes on the risk for diseases of the body systems.

    Methods

    Based on a subset of UK Biobank dataset comprising 87 617 participants, 3 sleep dimensions including 6 sleep indicators were obtained through a wrist-worn accelerometer, that is sleep duration and onset, sleep rhythm (relative amplitude and stability), and sleep quality (sleep efficiency and number of awakenings). Latent profile analysis (LPA) was applied to identify and classify distinct sleep modes. Then their longitudinal medical records were the association between different sleep modes and the risk for 467 diseases.

    Results‍

    LPA identified 5 subgroups of unique sleep modes in the participants. Among the 5 subgroups, the subgroup 4 had relatively optimal levels in above sleep indicators. Compared to the subgroup 4, the other 4 subgroups exhibited variations in different sleep dimensions, with at least one indicator demonstrating an unfavorable trend. These subgroups also revealed differences in racial composition, shift work and social deprivation index. Moreover, there were notable differences in the risk of various system diseases among the subgroups (P<0.05). When compared to the subgroup 4, the other 4 subgroups exhibited an elevated risk for certain diseases (comprising a total of 126 diseases), with the diseases of the circulatory system, digestive system and musculoskeletal system most common. Among the 5 subgroups, the subgroup 2 (shorter sleep duration and later sleep onset) and the subgroup 5 (rhythm disorder) had the highest counts of associated risks, amounting to 85 and 91 types, respectively, but there was certain difference in their systematic composition.

    Conclusion‍

    There are different sleep modes within the participants, and the modes are potentially associated with an increased risk for diseases of body systems. Comprehensive interventions targeting overall sleep modes rather than single sleep indicator may yield obvious health benefits.

  • Monographic Reports
  • Yanchun ZHANG , Yan LIU , Rui WANG , Feilong WANG , Yue ZHAO , Fei LI , Tunan CHEN , Jishu XIAN
    doi: 10.16016/j.2097-0927.202410073
    Objective

    To verify the accuracy of a Non-Contact Sleep Monitoring Mattress (NCSMM) based on body movement during sleep in assessing sleep quality of patients before neurosurgery in order to provide a more portable and efficient assessment tool for clinical staff.

    Methods

    A single-arm trial was conducted on 114 inpatients admitted in our department selected with convenience sampling. Sleep quality data of 1 night were collected through 5 sleep quality assessment tools, including NCSMM, polysomnography (PSG), Patient-Reported Outcome Measurement Information System (PROMIS) Sleep Disturbance scale, Richards-Campbell Sleep Scale (RCSQ), and a wearable device (smart watch for body movements and sleep quality monitoring). The sleep efficiency (≤85%) obtained by PSG was used as the diagnostic standard for sleep disorders. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and Youden index were calculated for the other 4 tools to evaluate and compare their diagnostic effectiveness.

    Results

    The AUC value for NCSMM, PROMIS, RCSQ and smart watch was 0.788 (95%CI: 0.687~0.888, P<0.001), 0.664 (95%CI: 0.543~0.784, P=0.02), 0.723 (95%CI: 0.600~0.846, P=0.001) and 0.750 (95%CI: 0.654~0.846, P<0.001), respectively. The diagnostic accuracy rate was 0.774, 0.559, 0.742 and 0.602, with corresponding Youden index value of 0.488, 0.321, 0.456, and 0.459. NCSMM demonstrated the best AUC value, sensitivity and Youden index when compared with the other 3 tools.

    Conclusion

    NCSMM shows high accuracy in assessing sleep quality in pre-neurosurgery inpatients, and it is a viable portable and efficient assessment tool in clinical practice.

  • Basic Medicine
  • Shulin LIU , Jing WEI , Baohang ZHU , Yan YE , Jiale PAN , Anni ZHAO , Zhen SONG , Liusheng PENG , Haibo LI , Hongwu SUN , Quanming ZOU
    doi: 10.16016/j.2097-0927.202412021
    Objective

    To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule, ophiopogonin, on enhancing the immune response of a subunit vaccine with the receptor-binding domain (RBD) of coronavirus spike protein as the antigen.

    Methods

    CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D' (OPD') on bone marrow-derived dendritic cells (BMDCs). Female Balb/c mice were randomly divided into RBD, RBD/OPD', RBD/Alum, and control groups. The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse, and immunization was carried out according to the intramuscular injection immunization procedure on days 0, 21, and 42. The titers of specific IgG and its subtype antibodies were detected by ELISA. The cytokine levels in the supernatant of splenocytes were detected using ELISA. The number of splenocytes secreting IFN-γ was detected by ELISpot. Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs. The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry. The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.

    Results

    When the concentration of OPD' was less than 5 μg/mL, the survival rate of BMDCs was 100%. After a single intramuscular injection in mice, except for a slight decrease in body weight, the other biochemical indicators were within corresponding normal ranges. After intramuscular injection immunization of the vaccine, the titers of serum-specific IgG, IgG1, and IgG2a in the RBD/OPD' group were significantly higher than those in the RBD group (P<0.05). Compared with the RBD group, the RBD/OPD' group induced a high-level Th1 cell immune response of IL-1β, TNF-α, and IFN-γ (P<0.01) and had more lymphocytes secreting IFN-γ (P<0.001). Laser confocal microscopy displayed that BMDCs took up more antigens after OPD' treatment, which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate (P<0.01). Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD' group than the RBD group, suggesting that OPD' may activate the PPAR signaling pathway to exert its adjuvant effect.

    Conclusion‍

    OPD' effectively enhances the immune response of the RBD subunit vaccine, and its action mechanism may be related to the activation of the PPAR signaling pathway.

  • Medical Psychology
  • Rongqian LIU , Li PENG , Yanli CHEN , Ying YANG , Jia XIAO , Jun JIANG , Chen XU , Qiao ZHANG , Min LI
    doi: 10.16016/j.2097-0927.202407004
    Objective

    To investigate the characteristics of attentional bias towards cancer-related stimuli in breast cancer patients with fear of cancer recurrence (FCR) under subthreshold and suprathreshold stimulus conditions.

    Methods

    A total of 94 female breast cancer patients admitted in First Affiliated Hospital of Army Medical University from September 2022 to March 2023 were recruited to complete the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) and the dot-probe task. According to the FCRI-SF cut-off score of 13, they were divided into clinical and non-clinical FCR groups, with 47 cases in each group. One-sample t-test and repeated-measures ANOVA were used to statistically analyze the subjects in the 2 groups in terms of attentional bias score, attentional orienting score and attentional disengagement difficulty score.

    Results

    The patients in the clinical FCR group showed a significant attentional bias toward cancer-related negative words (P<0.05). Under the subthreshold stimulus condition, its main component was attentional orienting to cancer-related negative words (P<0.05). In the suprathreshold stimulus condition, the main components were attentional orienting to neutral words matched by cancer-related negative words and difficulty in attentional disengagement from cancer-related negative words as well as attentional avoidance for cancer-related positive words (P<0.05).

    Conclusion

    Breast cancer patients with clinical FCR have an attentional bias toward cancer-related negative stimuli. Reducing their attention to cancer-related negative stimuli may be an effective measure to reduce FCR level in the patients.

  • Medical Psychology
  • Xiao CUI , Song CHANG , Heqing HUANG , Ling ZHU
    doi: 10.16016/j.2097-0927.202402078
    Objective

    To identify and delineate the developmental trajectories of depressive symptoms in the middle-aged and elderly population in China, and to explore the risk factors for depressive symptom trajectories in China's middle-aged and elderly population.

    Methods

    According to our inclusion and exclusion criteria, 7 600 participants were subjected based on the data from the China Health and Aged Care Tracking Survey (CHARLS) published by Peking University. The data from 5 waves of the survey from 2011 to 2023 were collected and analyzed with latent growth curve model (LGCM), latent class growth model (LGCM) to identify the developmental trajectories of depressive symptoms in the participants. Multicategorical logistic regression analyses were conducted to analyze whether gender, marital status, educational level, urban/rural residence, annual income, self-rated health status, and childhood bullying experience were risk factors for different trajectories of depressive symptoms.

    Results

    Two developmental trajectories of depressive symptoms were identified and classified in this study, that is, low-level stable (n=5 545, 72.96%) and high-level ascending (n=2 055, 27.04%). With the low-level stable group as a reference, multicategorical logistic regression analysis revealed that female (OR=1.373, 95CI%: 1.191~1.584, P<0.001), residence of rural area (OR=1.634, 95CI%: 1.410~1.895, P<0.001), and poor self-rated health status (OR=2.059, 95%CI: 1.890~2.243, P<0.001), and experience of childhood bullying (OR=1.76, 95%CI: 1.489~2.080, P<0.001) were associated with an increased risk of high-level ascending trajectory of depression.

    Conclusion

    There are 2 different trajectories of depressive mood in Chinese middle-aged and elderly population. And poor self-rated health status, history of childhood bullying, being female, and residence of rural area are risk factors for a high-level ascending trajectory of depressive symptoms.

  • Public Health and Preventive Medicine
  • Hao YUAN , Xiao LI , Zhiyu SUN , Aiwu WEI
    doi: 10.16016/j.2097-0927.202405107
    Objective

    To explore the causal relationships of anxiety, depression and neuroticism with recurrent spontaneous abortion (RSA).

    Methods

    Genome-wide association study (GWAS) data were used to extract single nucleotide polymorphisms (SNPs) closely related to anxiety, depression and neuroticism as instrumental variables (IVs). Inverse variance weighting (IVW), weighted median estimator (WME), weighted mode (WM) and Mendelian randomization (MR)-Egger regression were employed for MR analysis to evaluate the causal effects of anxiety, depression and neuroticism with RSA, and to analyze heterogeneity, gene pleiotropy and sensitivity.

    Results

    A total of 46 SNPs were extracted from GWAS data as IVs (5 anxiety SNPs, 9 depression SNPs, and 32 neuroticism SNPs). IVW, WME, WM and MR-Egger regression analysis revealed that the odds ratio (OR) and 95% confidence interval (CI) of anxiety data were 1.07 (0.86-1.32), 1.10 ( 0.85-1.43), 1.14 (0.81-1.59) and 1.18 (0.53-2.61); those of depression data were 1.11 (0.93-1.32), 1.05 (0.83-1.32), 0.96 (0.67-1.38) and 0.57 (0.25-1.31); those of neuroticism data were 1.01 (0.75-1.36), 1.07 (0.73-1.56), 1.02 (0.49-2.12) and 2.40 (0.46-12.44), but none of the above causal analyses were statistically significant (all P>0.05). After reliability analysis, the Cochran's Q test for heterogeneity evaluation was not significant (P>0.05), the MR-Egger regression intercepts for gene pleiotropy evaluation were all close to 0 (P>0.05), and the sensitivity evaluation "Leave-one-out" test also shows that the combined causal effect values are similar.

    Conclusion

    There dose not exist causal relationships of anxiety, depression and neuroticism with RSA. The reliability test shows that the results are relatively robust.