Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

To explore the regulatory mechanism of drought stress on the synthesis of chlorogenic acid and luteoloside in Lonicera japonica, we designed five drought gradients (soil water contents of 30%, 24%, 17%, 14%, and 10%) and screened and verified the differentially expressed genes (DEGs) by RNA sequencing (RNA-seq) and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we employed HPLC to systematically measure the content changes of chlorogenic acid and luteoloside. The results revealed that drought significantly reduced the accumulation of secondary metabolites, and severe drought led to more obvious reductions. Under extreme drought (soil water content of 10%), the content of chlorogenic acid and luteoloside decreased significantly to 25.73 mg/g and 11.33 mg/g (with the decrease rates of 37.85% and 9.58%, respectively). A total of 77 454 genes were identified via transcriptome analysis, among which the number of DEGs reached 1 128 under the extraordinary drought. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed that the DEGs were mainly involved in flavonoid synthesis, secondary metabolite biosynthesis, plant hormone signal transduction and the plant-pathogen interaction pathways, and the expression of key genes regulating the synthesis of chlorogenic acid and luteoloside was significantly downregulated. RT-qPCR verified the accuracy of the RNA-seq data. This study revealed that drought stress reduced the content of chlorogenic acid and luteoloside, the main secondary metabolites, by inhibiting the expression of key genes in the secondary metabolism pathways. The findings provide candidate gene resources for molecular breeding of drought-tolerant Lonicera japonica.
Lonicera/physiology* ; Chlorogenic Acid/metabolism* ; Droughts ; Stress, Physiological ; Gene Expression Regulation, Plant ; Glucosides/metabolism* ; Luteolin

Objective To investigate the correlation between the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)and connective tissue growth factor(CTGF)in serum and cognitive function and clinical symptoms in patients with schizophrenia.Methods A total of 160 patients with schizophrenia who were diagnosed and treated in Department of Mental Intensive Care of Wuhan Wudong Hospital from January 2021 to January 2023 were collected as the observation group,and 160 healthy volunteers who underwent physical examinations were collected as the control group for the study.According to the Positive and Negative Symptom Scale(PANSS),patients were evaluated for their clinical and psychiatric symptoms(positive and negative symptoms,general pathological symptoms,and additional symptoms).The patients were grouped into a high score group(PANSS total score≥70 points,n=72)and a low score group(PANSS total score＜70 points,n=88).MATRICS consensus cognitive battery(MCCB)was applied to evaluate the cognitive abilities of patients;enzyme-linked immunosorbent assay(ELISA)was applied to detect serum P2X7R and CTGF levels.Spearman method was applied to analyze the correlation between serum P2X7R,CTGF levels and PANSS scores,and MCCB scores in patients with schizophrenia.Results Compared with the control group,the serum levels of P2X7R(610.71±107.83ng/L vs 384.78±80.62 ng/L)and CTGF(1.85±0.36μg/L vs 1.40±0.21μg/L)in the observation group were increased,with differences of statistical significance(t=21.226,13.658,all P＜0.05).The scores of variety items of MCBB of patients with schizophrenia in the observation group were lower than those in the control group,with differences of statistical significance(t=14.845～24.862,all P＜0.05),the positive symptom score(21.10±3.42score),negative symptom score(23.37±5.03 score),general pathological symptom score(39.48±8.11score),additional symptom score(8.26±1.22 score),and PANSS total score(92.21±12.50score)of schizophrenia patients in the high group were higher than those in the low group(13.65±3.04,15.62±3.91 score,30.14±6.15 score,5.20±0.94score,64.61±5.30score),with differences of statistical significance(t=14.576,10.964,8.280,17.915,18.764,all P＜0.05).The serum levels of P2X7R and CTGF in patients with schizophrenia in the high group were higher than those in the low group,with differences of statistical significance(t=12.233,5.923,all P＜0.05).The levels of serum P2X7R and CTGF in patients with schizophrenia were positively correlated with PANSS score(r=0.464～0.580,all P＜0.05),and negatively correlated with MCCB score[r=-0.603～-0.439,all P＜0.05].Conclusion The serum levels of P2X7R and CTGF in patients with schizophrenia are elevated,they are closely related to the clinical symptoms and cognitive function of patients.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

Objective:To investigate the performance of medical students with different cognitive styles and temperament types in the flipped classroom of pediatrics.Methods:A total of 85 medical students of the class of 2018 in eight-year program who studied the course of Pediatrics 2 in West China Medical School, Sichuan University, were selected and received the flipped classroom teaching of pediatrics. The cognitive style figure test was used to investigate the cognitive style of students, and the temperament self-test questionnaire was used to investigate the temperament type of students. The methods such as the cluster analysis, the ANOVA analysis of variance, the Pearson correlation analysis, and the chi-square test were used to describe the distribution of flipped classroom scores and related differences between the students with different cognitive styles and temperament types.Results:There were four temperament types of these students, i.e., choleric and sanguine temperament, sanguine and phlegmatic temperament, melancholic temperament, and choleric temperament, accounting for 28.24%, 23.53%, 27.06%, and 21.18%, respectively. There were two cognitive styles of field independence and field dependence, accounting for 51.76% and 48.24%, respectively. There was a significant difference in flipped classroom scores between the students with different cognitive styles ( t=3.18, P<0.05), while there was no significant difference in such scores between the students with different temperament types ( F=0.38, P>0.05). The correlation analysis showed that the score of phlegmatic temperament was significantly negatively correlated with flipped classroom scores ( r=-0.283, P<0.05), and the score of cognitive test was significantly positively correlated with flipped classroom scores ( r=0.346, P<0.05). Conclusions:In the flipped classroom teaching of pediatrics, it is necessary to flexibly apply specific interaction and evaluation methods in students with different temperament types and cognitive styles and grasp the relationship between cooperative learning and independent learning. The design of different links of flipped classroom should be further improved.

The outbreak of COVID-19 as an acute communicable disease has also changed the epidemiological status of diabetes mellitus and other noncommunicable chronic diseases. During the COVID-19 epidemic period, it was observed that there were increased morbidity of diabetes, difficulties in blood sugar control and increased acute complications for diabetic patients. This may be attributed to lifestyle changes during the epidemics, such as the reduced exercise time and increased sedentary time, more snacks and sugary food intake, as well as anxiety and depression. However, it is not known the long-term impact of COVID-19 epidemic on the management of diabetic patients, so it is necessary to closely monitor the exposed diabetic patients in the future.

Objective:To analyze the clinical and genetic features of the children with 5p15.1-5p15.33 duplication at the end of the short arm of chromosome 5 (5p).Methods:Clinical data of a 5p15.1-5p15.33 duplicative patient diagnosed in the Department of Pediatric Intensive Care Unit of West China Second University Hospital of Sichuan University in July 2021 were collected, and the characteristics of the patients of 5p duplication syndrome reported in the literatures were summarized and analyzed.Results:The boy was 1 year and 5 months old at the time of admission. The main clinical manifestations included growth restriction and developmental delay after birth, accompanied by craniofacial deformities. At 7 months old, he was diagnosed as epilepsy due to convulsive limbs. At present, he is 2 years old, still has recurrent convulsions, can not raise his head, sit alone, crawl and talk, with hypotonia. Repeated cranial magnetic resonance imaging showed agenesis of the corpus callosum. The child′s parents had normal phenotypes. His copy number variation sequencing results showed partial overlap of chromosome 5p15.1-5p15.33 (chr5:1934522-18905656), which was determined as pathogenic copy number variation according to copy number variations evaluation criteria, and no abnormality was detected in his parents. According to the retrieval strategy set in this study, 10 literatures (all in English, reporting 17 cases) were retrieved, and a total of 22 5p duplication syndrome patients (including this case and 4 cases included in databases) were included. Seventeen of the 22 patients were younger than 14 years old with a onset age of 7 (0, 18) years, and the male to female ratio was about 1.1∶1. Among the 22 patients, craniofacial malformation was found in 19 patients, developmental disorder in 18, bone/muscle dysplasia in 15, autism in 11, attention deficit hyperactivity disorder in 9, mental retardation in 8, obesity in 5, epilepsy in 5, congenital heart dysplasia in 2, hypotonia in 4, strabismus/hyperopia in 2, and corpus callosum dysplasia, endocrine dysfunction, inguinal hernia as well as umbilical hernia in 1, respectively. There were 19 cases of multiple malformation and 3 cases of single malformation.Conclusions:5p15.1-5p15.33 duplication may be the genetic cause of this child. Facial malformation, developmental delay, skeletal/muscular dysplasia, intellectual disability, autism spectrum disorder and attention deficit hyperactivity disorder are the main clinical phenotypes of 5p copy number duplication. Corpus callosum dysplasia may be an extended phenotype of chromosome duplication at this location.

Objective:To analyze the risk factors for heart failure in patients with hemodialysis, and to construct a nomogram model.Methods:The clinical data of 218 patients with hemodialysis in Xianyang Central Hospital from January 2021 to April 2022 were retrospectively analyzed. Among them, 83 cases developed heart failure (heart failure group), and 135 cases did not develop heart failure (control group). The relevant clinical data were recorded, including age, sex, body mass index, disease duration, concurrent infection, blood calcium, blood phosphorus, soluble CD 146 (sCD 146), soluble growth-stimulated expression gene 2 protein (sST2), N-terminal brain natriuretic peptide precursor (NT-proBNP), time-averaged urea concentration (TACurea), tumor necrosis factor α (TNF-α), blood creatinine and 24 h urine volume. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of each index in predicting heart failure in patients with hemodialysis. Multivariate Logistic regression was used to analyze the independent risk factors of heart failure in patients with hemodialysis. R language software 4.0 "rms" package was used to construct the nomogram model for predicting the heart failure in patients with hemodialysis, the calibration curve was internally validated, and the decision curve was used to evaluate the predictive efficacy of the nomogram model. Results:There were no statistical difference in gender composition, age, body mass index, disease duration, 24 h urine volume and blood creatinine between the two groups ( P>0.05); the rate of concurrent infection, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea in heart failure group were significantly higher than those in control group: 39.76% (33/83) vs. 8.89% (12/135), (1.53 ± 0.34) mmol/L vs. (1.27 ± 0.24) mmol/L, (43.60 ± 10.24) μmol/L vs. (28.08 ± 7.99) μmol/L, (49.00 ± 9.41) μg/L vs. (34.53 ± 8.05) μg/L, (38.57 ± 6.79) μg/L vs. (29.72 ± 5.64) μg/L, (5.18 ± 0.92) μg/L vs. (4.07 ± 1.13) μg/L and (24.28 ± 4.37) mmol/L vs. (17.96 ± 2.52) mmol/L, the blood calcium was significantly lower than that in control group: (1.95 ± 0.36) mmol/L vs. (2.31 ± 0.39) mmol/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the optimal cut-off values of blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea for heart failure in patients with hemodialysis were 2.01 mmol/L, 1.42 mmol/L, 34.15 μmol/L, 40.37 μg/L, 35.37 μg/L, 4.33 μg/L and 20.74 mmol/L. Multivariate Logistic regression analysis result showed that the blood calcium (≤2.01 mmol/L), blood phosphorus (>1.42 mmol/L), sCD 146 (>34.15 μmol/L), sST2 (>40.37 μg/L), NT-proBNP (>35.37 μg/L), TNF-α (>4.33 μg/L) and TACurea (>20.74 mmol/L) were independent risk factors for heart failure in patients with hemodialysis ( OR = 1.183, 1.582, 1.915, 1.105, 1.459, 1.347 and 1.717; 95% CI 1.102 to 1.191, 1.274 to 1.868, 1.716 to 2.105, 1.072 to 1.141, 1.225 to 1.703, 1.132 to 1.574 and 1.482 to 1.935; P<0.05 or <0.01). The blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea were used as predictors to construct a nomogram model for predicting heart failure in patients with hemodialysis. Internal validation result showed that the nomogram model predicted the heart failure with good concordance in patients with hemodialysis (C-index = 0.811, 95% CI 0.675 to 0.948); the nomogram model predicted the heart failure in patients with hemodialysis at a threshold>0.18, provided a net clinical benefit, and all had higher clinical net benefits than blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea. Conclusions:The nomogram model constructed based on blood calcium, blood phosphorus, sCD 146, sST2, NT-proBNP, TNF-α and TACurea has better clinical value in predicting the heart failure in patients with hemodialysis.

Objective:To carry out the Meta-integration of real experience qualitative studies on modified electroconvulsive therapy (MECT) for patients with mental disorders.Methods:We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, WanFang Data, and China Biology Medline Disc by computer to collect qualitative researches on the MECT experience of patients with mental disorders from database establishment to February 18, 2022. The quality of articles was evaluated using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The results were summarized and integrated using the aggregation integration method.Results:This study included 16 articles and extracted 69 results. Similar results were summarized into 10 categories and integrated into 4 themes, namely MECT decision-making experience, different treatment attitudes, breaking the life normality, adjusting strategies to cope with the new normality and expecting diversified support and help.Conclusions:Medical and nursing staff should pay attention to the MECT experience of patients with mental disorders, and meet their needs through multiple channels. Medical and nursing staff also should cooperate with patients' family members and peers to build a diversified support system to provide patients with necessary support and help them cope with the new forms of life.