Latest ArticlesTo investigate the expression of calumenin (CALU) in gastric cancer and its effect on metastasis and invasion of gastric cancer, and analyze its relationship with the prognosis of gastric cancer patients.
The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis. A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022. The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay, and the relationship of its expression with clinicopathological parameters was statistically analyzed. After gastric cancer cells with CALU knockdown and overexpression were constructed, and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR. Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells.
Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues (P<0.05), and its expression level was negatively correlated with the prognosis of patients (P<0.05). Immunohistochemical results showed that the expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues (P<0.01), and its level was positively correlated with the depth of infiltration (P<0.01), lymph node metastasis (P<0.01), and TNM stage (P<0.05). Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage (P=0.021) and T stage (P<0.001) and N stage (P=0.028). CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells (P<0.01), while over-expression obtained the opposite results.
CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.
To analyze clinical characteristics of mesenchymal-subtype gastric cancer (Mes-GC) by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.
Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023. Transcriptome and genome sequencing were applied for these tissue samples, including 19 cases of diffuse-type gastric cancer, 22 cases of intestinal-type gastric cancer, and 23 cases of mixed-type gastric cancer patients. Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer (non-Mes-GC) by integrating data resources including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and National Genomics Data Center (NGDC).
Compared to non-Mes-GC patients, Mes-GC ones were characterized by later clinical stages, deeper tumor infiltration, and higher rates of lymph node metastasis. Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time, poor prognosis as well as increased risk of cancer recurrence (P<0.05). Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness, metastasis (P<0.05), and epithelial-mesenchymal transition (EMT). And in the tumor microenvironment, there were significant more myeloid cells, smooth muscle cells, endothelial cells and fibroblasts, with the most pronounced elevation in the proportion of fibroblasts (P<0.05). Moreover, the patients with larger proportion of fibroblasts were associated with poorer prognosis.
Mes-GC tumor cells exhibit higher stemness and EMT characteristics, and stromal cells such as myeloid cells, endothelial cells, and fibroblasts are enriched in the tumor microenvironment. These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.
To construct an in vitro co-culture model of gastric cancer organoids and cancer-associated fibroblasts (CAFs), and investigate the role of cancer-associated fibroblasts in the proliferation and chemotherapy resistance of gastric cancer organoids.
Tumor tissues from 12 gastric cancer patients undergoing surgical treatment in Department of General Surgery of Second Affiliated Hospital of Army Medical University from February 2023 to March 2024 were collected to construct gastric cancer organoids using 3D culture. HE staining was used to observe the morphology, and immunohistochemical assay was employed to determine the expression of cytokeratin CK7, carcinoembryonic antigen (CEA), and proliferation marker Ki-67. After CAFs derived from the same patient were cultured, observed for their morphology under a light microscope, and detected for the phenotype by flow cytometry, the cells were co-cultured with gastric cancer organoids in a 1:1 ratio. Phase-contrast microscopy was applied to observe the growth of the organoids and analyze the number, average diameter, and total area. Then, organoids cultured alone served as the control group. After the control and co-culture groups were treated with chemotherapy drugs, 5-fluorouracil and oxaliplatin, for 48 h, the viability and apoptosis of organoids were assessed with CellTiter-Glo® 3D assay and CellEvent™ Caspase 3/7 activity, respectively.
Gastric cancer organoids and CAFs were successfully established from 10 gastric cancer patient-derived samples. The gastric cancer organoids exhibited morphological characteristics consistent with the corresponding primary tumors, and showed positive expression of CK7, CEA, and Ki-67. CAFs displayed typical spindle-shaped morphology and exhibited the phenotypic markers CD326-, CD45-, CD31-, α-SMA+, CD73+, CD90+, and CD105+. Compared to the organoids cultured alone, the organoids co-cultured with CAFs showed more formation of organoids, in larger average diameter, and taking larger total area (P<0.05). After the treatment of 5-fluorouracil and oxaliplatin, the half-maximal inhibitory concentration (IC50) was 10.66 and 3.26 μmol/L, respectively in the control group, while was 46.23 and 91.11 μmol/L in the co-culture group. Additionally, the number of CellEvent™ Caspase 3/7 positive apoptotic cells was significantly less in the co-culture group than the control group.
Compared with individually cultured gastric cancer organoids, the co-culture model of gastric cancer organoids and CAFs better simulates the pro-tumor proliferation and drug resistance effects of in vivo tumor microenvironment.
To explore the risk factors of hospitalization within 24 h after birth and respiratory support in late preterm and term neonates.
A case-control study was conducted on 1 468 neonates with gestational ages ≥34 weeks and <42 completed weeks delivered at the University-Town Hospital of Chongqing Medical University from January 2023 to March 2024. Maternal health parameters and neonatal outcomes were systematically obtained through standardized case report forms during the study period. The neonates were stratified into the hospitalization group and the non-hospitalization group based on neonatal ward admission within 24 h. For those hospitalized with infectious diseases, subgroup analysis was conducted with further categorization into respiratory support and the non-respiratory support subgroups according to ventilatory assistance requirements. The perinatal risk factors were compared between groups and subgroups, and the independent risk factors for hospitalization and the need for respiratory support within 24 h in neonates were identified. The indicators with P<0.1 in the univariate analysis were included in the multivariate logistic regression analysis, and the stepwise regression analysis was used to fit the multivariate logistic regression model.
There were 213 cases (14.5%) in the hospitalization group and 1 255 cases (85.5%) in the non-hospitalization group. A total of 150 neonates were hospitalized due to infectious diseases, including 48 cases (32.0%) in the respiratory support subgroup and 102 cases (68.0%) in the non-respiratory support subgroup. The multivariate logistic regression analysis showed that non-regular maternal prenatal examination (OR=2.687, 95%CI: 1.175~6.141, P=0.019), intrauterine growth retardation (OR=2.711, 95%CI: 1.106~6.646, P=0.029), premature rupture of membranes (OR=1.667, 95%CI: 1.139~2.438, P=0.008), chorioamnionitis (OR=4.852, 95%CI: 2.114~11.135, P<0.001), infectious diseases in the first week before delivery (OR=1.531, 95%CI: 1.015~2.310, P=0.042), turbidity of amniotic fluid (OR=3.170, 95%CI: 2.099~4.787, P<0.001), abnormal placenta (OR=2.335, 95%CI: 1.202~4.534, P=0.012), complications during pregnancy (OR=2.367, 95%CI: 1.360~4.118, P=0.002), and the use of glucocorticoids before delivery (OR=2.744, 95%CI: 1.219~5.528, P=0.009) were positively correlated with hospitalization within 24 h postnatally in late preterm and term neonates. Gestational age (OR=0.693, 95%CI: 0.602~0.797, P<0.001), 5-minute Apgar score (OR=0.026, 95%CI: 0.003~0.212, P=0.001), umbilical cord blood pH (OR=0.044, 95%CI: 0.002~0.793, P=0.034), and umbilical cord blood BE (OR=0.885, 95%CI: 0.823~0.823, P=0.001) were negatively correlated with it. Premature rupture of membranes (OR=0.207, 95%CI: 0.070~0.618, P=0.005), infectious diseases in the first week before delivery (OR=0.245, 95%CI: 0.070~0.854, P=0.027), 5-minute Apgar score (OR=0.063, 95%CI: 0.008~0.526, P=0.011), and abnormal C-reactive protein of newborns (OR=0.145, 95%CI: 0.046~0.460, P=0.001) were negatively correlated with the need for respiratory support in neonates hospitalized due to infectious diseases.
Risk factors for neonatal hospitalization within 24 h postnatal late preterm and term are identified as irregular antenatal care, fetal growth restriction and premature rupture of membranes in late preterm and term neonates. premature rupture of membranes, antenatal maternal infections within 1 week prior to delivery and 5-minute Apgar score ≥7 emerge as significant protective factors against respiratory support requirement in neonates hospitalized with infectious diseases.
To explore the efficacy of goal management training (GMT) on core symptoms and mental status in college students with attention deficit hyperactivity disorder (ADHD) inattentive type.
Delphi method was used to construct a GMT program for college students with inattentive ADHD. Then, totally 68 college students with inattentive ADHD were recruited through advertisements published by hospitals and universities (Second Affiliated Hospital of Army Medical University, and 3 universities in Chongqing from March to June 2024. The subjects were randomly divided into an intervention group (n=34) and a control group (n=34). The intervention group received GMT for 2 h, once a week, for 7 weeks, and the control group did not receive training for the time being. The 2 groups were evaluated within 1 week before and in 7 weeks after intervention by using Adult ADHD Self-Report Scale (ASRS), Dysregulation of Emotions Rating Scale (DERS), Generalized Anxiety Disorde-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Self-Compassion Scale (SCS), and Satisfaction with Life Scale (SWLS).
① The expert authority coefficient (Cr) of 2 rounds of expert consultation was 0.83, with a questionnaire recovery rate of 100% and 95%, respectively, the Kendall’s coordination coefficient was 0.081 (P<0.01) and 0.226 (P<0.01), and the coefficient of variation was <0.3, indicating the results of the expert consultation were reliable. The constructed GMT program includes 1 first-level indicator, 7 second-level indicators, and 20 third-level indicators. ② After 7 weeks of GMT intervention, the interaction between the 2 groups and time showed that the experimental group obtained significant improvements than the control group in terms of inattention symptoms (Wald Chi-square=28.35, P<0.001), dysregulation of emotions (Wald Chi-square=23.81, P<0.001), anxiety (Wald Chi-square=22.79, P<0.001), depression (Wald Chi-square=20.52, P<0.001), self-compassion (Wald Chi-square=9.36, P<0.01), and life satisfaction (Wald Chi-square=3.97, P<0.05).
GMT intervention can significantly improve the core symptoms of college students with inattentive ADHD, reduce anxiety and depression levels, enhance their emotion regulation and self-compassion abilities, and improve their life satisfaction.
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.
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.
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.
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.
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.
During NREM sleep, RE inputs may participate in the generation of sleep spindles network oscillations in the mPFC by activating interneurons.
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.
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.
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).
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.
To investigate the impact of sleep modes on the risk for diseases of the body systems.
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.
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.
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.