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.

OBJECTIVE: To investigate the relationship between peripheral blood circular RNA Bardet-Biedl syndrome 9 (circBBS9) and circRNA catenin beta 1 (circCTNNB1) and weaning failure of mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A prospective, observational cohort study was conducted. The patients with AECOPD who received invasive mechanical ventilation and passed the spontaneous breathing test (SBT) admitted to the First Affiliated Hospital of Hebei North University from January 2022 to February 2024 were selected as the study subjects. According to the outcome of weaning, the patients were divided into failed weaning group and successful weaning group. At admission and before SBT, the expression levels of circBBS9 and circCTNNB1 in peripheral blood were detected by fluorescence quantitative polymerase chain reaction (PCR). General information, acute physiology and chronic health evaluation II (APACHEII) score within 24 hours of admission, vital signs before SBT and the most recent laboratory indicators before SBT of the patients were collected. The differences in circBBS9 and circCTNNB1 expression levels and clinical data between the two groups were compared. Multivariate Logistic regression was used to analyze the influencing factors of the weaning failure. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of each index on weaning failure. RESULTS: Ultimately, 132 patients with AECOPD who underwent invasive mechanical ventilation and passed the SBT were enrolled in the study. Among them, 82 patients were successfully weaned from mechanical ventilation, while 50 patients failed to be weaned, resulting in a weaning failure rate of 37.88%. There was no statistically significant difference in the expression levels of circBBS9 and circCTNNB1 in the peripheral blood at admission of patients between the two groups. The expression level of circBBS9 in the peripheral blood before SBT of patients in the failed weaning group was significantly higher than that in the successful weaning group (2^-ΔΔCt: 131.64±30.24 vs. 100.00±21.32), and the expression level of circCTNNB1 was significantly lower than that in the successful weaning group (2^-ΔΔCt: 79.90±16.82 vs. 100.00±26.43), and the differences were statistically significant (both P < 0.05). The APACHEII score within 24 hours of admission and the levels of RSBI, SCr, and PCT before SBT in the failed weaning group were significantly higher than those in the successful weaning group [APACHEII score: 22.54±4.62 vs. 16.56±4.58, RSBI: 81.90±16.56 vs. 63.25±17.00, SCr (μmol/L): 100.20±17.27 vs. 89.93±26.29, PCT (μg/L): 1.08±0.18 vs. 0.87±0.22], and the Alb level before SBT was significantly lower than that in the successful weaning group (g/L: 29.71±2.73 vs. 33.93±2.89), and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in other clinical data between the two groups. Multivariate Logistic regression analysis showed that circBBS9 [odds ratio (OR) = 1.291, 95% confidence interval (95%CI) was 1.049-1.588] and APACHEII score (OR = 2.897, 95%CI was 1.004-8.353), RSBI (OR = 1.413, 95%CI was 1.057-1.890) were independent risk factors for weaning failure (all P < 0.05), and circCTNNB1 (OR = 0.812, 95%CI was 0.688-0.959) and Alb (OR = 0.149, 95%CI was 0.036-0.614) were protective factors (both P < 0.05). ROC curve analysis showed that circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb all had certain value for predicting weaning failure. The area under the ROC curve (AUC) and 95%CI were 0.820 (0.750-0.890), 0.755 (0.674-0.835), 0.827 (0.757-0.897), 0.795 (0.715-0.876), and 0.854 (0.791-0.919), respectively. Using the multivariate Logistic regression equation as the combined indicator, the AUC for predicting weaning failure reached 0.997 (95%CI was 0.993-1.000), which was significantly higher than that of the single indicators including circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb (the Z value was 5.582, 6.093, 5.771, 5.932, and 5.182, respectively, all P < 0.05). CONCLUSIONS High expression of circBBS9 and low expression of circCTNNB1 in the peripheral blood of AECOPD patients receiving invasive mechanical ventilation before SBT are associated with weaning failure. circBBS9, circCTNNB1 combined with APACHEII score, RSBI and Alb are helpful for predicting the failure of weaning in these patients.
Humans ; Pulmonary Disease, Chronic Obstructive/blood* ; Prospective Studies ; Ventilator Weaning ; RNA, Circular/blood* ; Respiration, Artificial ; Male ; Female ; Aged

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of age.The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process.Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism.Therefore,maintaining mitochondrial homeostasis is an important strategy to mitigate OA.Mitophagy is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial homeostasis.Cumulative studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA.By reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

The endoplasmic reticulum is a key site for protein production and quality control.More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum.However,during protein folding,unfolded and/or misfolded proteins are prone to occur,which may lead to endoplasmic reticulum stress.Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control(ERQC)and endoplasmic reticulum-associated degradation(ERAD),which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins.The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored.Therefore,this paper reviews the process and function of protein folding and ERAD in mammalian cells,in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

Transcatheter aortic valve implantation (TAVI) is an important alternative in treating high-risk patients with aortic valve regurgitation. Transcatheter tricuspid valve implantation (TTVI) is also an important treatment option for high-risk patients with tricuspid regurgitation. We reported a 72-year male patient who underwent TAVI due to severe aortic valve regurgitation using a J-Valve. During a two-year follow-up, the patient developed secondary tricuspid regurgitation to atrial fibrillation, and subsequently received TTVI using a LuX-Valve. Following the interventions, the patient's symptoms were significantly improved, and echocardiography indicated good hemodynamic performance of both transcatheter heart valves. This case highlights the feasibility and effectiveness of performing multiple valve implantations via transcatheter approaches in high-risk elderly patients.

Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.

Objective     To investigate the effect and prognosis of patients with ventricular septal rupture after myocardial infarction treated by surgical repair combining an occluder and a patch. Methods     Clinical data of 42 patients with myocardial infarction complicated with ventricular septal rupture admitted to the First Affiliated Hospital of Zhengzhou University from January 2010 to September 2021 were retrospectively analyzed. According to the surgical methods, 27 patients were divided into a traditional group, including 17 males and 10 females, with an average age of 62.81±6.81 years, who were repaired by patch only, and 15 patients were divided into a modified group, including 11 males and 4 females, with an average age of 64.27±9.24 years, who were repaired by surgery combining an occluder and a patch. Perioperative and follow-up data of the two groups were compared and analyzed. Results     There were statistical differences between the two groups in preoperative Killip grading, rate of intra-aortic balloon pump use, interval from myocardial infarction to operation, and the number of culprit artery (P<0.05). There was no statistical difference in other preoperative data, the cardiopulmonary bypass time, aortic cross-clamping time, postoperative hospital stay or in-hospital death rate between the two groups (P>0.05). No residual shunt occurred in the modified group, and the difference was statistically significant compared with the traditional group (P=0.038). There was no statistical difference in other complications between the two groups (P>0.05). The median follow-up time was 4 years. Two patients in the traditional group and one in the modified group died during follow-up. The follow-up cardiac function grading of patients in the modified group was statistically different from that in the traditional group (P=0.023). Conclusion     The perioperative  mortality of ventricular septal rupture after myocardial infarction is high, but the long-term effect is satisfactory. Surgical repair combining an occluder and a patch is a safe and effective treatment for ventricular septal rupture, which can effectively reduce postoperative residual shunt.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for severe aortic stenosis. The localization and anchor of many transcatheter heart valves available in the clinic today are dependent on the calcific aortic valve leaflet of patients. We reported here a successful case of transapical aortic valve implantation with Ken-Valve heart valve in an 82-year-old male patient with pure severe aortic regurgitation without native valve calcium. Postoperative follow-up (3 months after the surgery) showed that the cardiac function significantly improved. The echocardiography indicated that the Ken-Valve prosthesis worked well without perivalvular regurgitation. The short-term clinical effect was satisfactory. The Ken-Valve with three position anchors is proved to be suitable for the treatment of pure aortic regurgitation.