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 analyze the expression of long-chain non-coding RNA U73166 in lung cancer tissues and its relationship with patients′ prognosis, and to explore the effects of silencing U73166 on proliferation and invasion of lung cancer H1299 cells and its regulatory mechanism. Methods:The expression level of U73166 in lung cancer tissues and normal tissues, as well as its correlation with lung cancer patients′ overall survival, were analyzed using the gene expression profiling interactive analysis (GEPIA) database. After culturing, H1299 cells were divided into a control group and a transfection group based on treatment conditions, and were transfected with 25 μmol/L of U73166 negative control and U73166 inhibitor, respectively. The effects of silencing U73166 on the relative expression of U73166 and microRNA-618 ( miR-618) genes in H1299 cells were assessed by real-time reverse transcription-PCR method. A cell counting kit-8 assay was used to evaluate the impact of silencing U73166 on the viability of H1299 cells. A transwell invasion assay was performed to detect the invasive ability of H1299 cells. The Linc2GO database and a dual-luciferase reporter assay were used to predict and verify the binding site between U73166 and miR-618. Western blotting was used to analyze the relative expression of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and phosphorylated signal-transducing adaptor molecule 1 (p-STAM1) in the JAK2/STAT3 signaling pathway to evaluate the effects of silencing U73166 on this pathway in H1299 cells. Data were analyzed by an independent sample t test or one-way analysis of variance. Results:Analysis of the GEPIA database revealed that U73166 relative expression level in lung cancer tissues ( n=383) was significantly higher than that in normal tissues ( n=347) ( P<0.01). The overall survival of lung cancer patients with low U73166 expression [(245±2) months] was longer than that of patients with high U73166 expression [(167±2) months] ( P<0.05). The relative expression of U73166 were 7.81±0.99 in the control group and 1.01±0.26 in the transfection group, respectively, and the relative expression of miR-618 were 1.03±0.20 in the control group and 4.83±1.27 in the transfection group, respectively. Silencing U73166 significantly downregulated its expression ( t=6.66, P<0.01) and upregulated the relative expression of miR-618 ( t=2.96, P<0.01) in H1299 cells. After silencing U73166, the absorbance values of H1299 cells in the transfection group on days 2, 3, 4, and 5 (0.36±0.04, 0.74±0.05, 1.07±0.09, and 1.18±0.10) were significantly lower than those in the control group (0.55±0.03, 1.20±0.08, 1.63±0.07, and 1.90±0.07) ( P<0.05, 0.01). The number of invasive cells in the control and transfection groups were 52.03±6.08 and 19.92±3.78, respectively. There were significantly fewer invasive cells in the transfection group ( t=4.49, P<0.01). After transfection with wild-type U73166, the relative luciferase activity in the miR-618 group (0.32±0.05) was significantly lower than that in the miR-negtive control group (0.96±0.15) ( t=4.02, P<0.01). However, after transfection with mutant U73166, there was no statistically significant difference in relative luciferase activity between the miR-618 group (1.01±0.15) and the miR-negtive control group (1.03±0.11) ( t=0.09, P>0.05). The relative expression of p-JAK2, p-STAT3, and p-STAM1 proteins in the transfection group were 2.08±0.21, 1.36±0.20, and 0.55±0.12, respectively. These values were significantly lower than those in the control group (3.72?±?0.29, 5.56?±?0.19, and 4.38±0.17) (all P<0.01). Conclusions:U73166 is highly expressed in lung cancer tissues and lung cancer cells, and its expression is related to lung cancer patients′ overall survival. Silencing U73166 can target miR-618, which inhibits the proliferation and invasion of H1299 cells.

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.

Polycystic ovary syndrome(PCOS)is a heterogeneous disorder closely associated with reproductive endocrine dysfunction in the women.The etiology and pathogenesis of PCOS remain unclear.PCOS is the result of the combination of endocrine metabolic disorders,genetics,and environmental factors.Hyperandrogenemia(HA)and insulin resistance(IR)are the fundamental pathophysiological changes in the development of PCOS,and their interactions exacerbate the clinical manifestations of the PCOS patients.The family aggregation and twin study results confirm the genetic predisposition of PCOS;the genome-wide association study(GWAS)results confirm some risk loci and candidate genes of PCOS.The unhealthy lifestyle habits and environmental endocrine disruptors also play an important role in the progression of PCOS,and the gut microbita is involved in the pathogenesis of PCOS.This article provides a comprehensively retrospective analysis on the recent studies about PCOS,and reviews both internal factors and external factors related to the etiology and pathogenesis of PCOS.

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 prepare dual-targeted lipid ultrasound microbubbles loaded with ANM33 (HA-PANBs) and evaluate its feasibility in targeting foam cells by stages and achieving precise intracellular drug release in vitro. Methods:The dual-targeteded lipid ultrasound microbubbles were designed with nanobubbles (NBs) as the microbubble core, hyaluronic acid (HA) as the first-stage targeting ligand for damaged endothelial cells, aptamer PM1 as the second-stage targeting moiety for foam cells, and ANM33 as the therapeutic factor. Simultaneously with the characterization of the lipid bubbles, the stability and in vitro contrast-enhanced ultrasound imaging capability were detected. Then a co-culture model of damaged human umbilical vein endothelial cells (HUVEC) and macrophages (RAW264.7, MΦ) was established, combined with flow cytometry, oil red O staining and small animal in vivo imaging to evaluate the ability of HA-PANBs in targeting foam cells precisely and releasing ANM33. Results:The HA-PANBs exhibited regular morphology and good structural stability, with a particle size of (1 357.53±140.20)nm and a surface potential of (-5.61±0.73)mV. HA, PM1 and ANM33 were effectively connected. In the damaged HUVEC/MΦ co-culture system, the HA-PANBs group demonstrated the best targeting effect on foam cells, with an effective uptake of (80.65±2.12)%, which was 56.74% higher than that of the NBs group. Oil red O staining revealed that the cholesterol efflux capacity of foam cells in the HA-PANBs group was significantly better than that in the NBs group, the results were statistically different [(629.80±21.99) a.u.vs (1 071.00±55.49)a.u., P<0.05]. Conclusions:The dual-targeted lipid ultrasound microbubbles (HA-PANBs) can precisely target foam cells and significantly enhance their cholesterol efflux, providing a new strategy for the early non-invasive diagnosis and treatment of atherosclerosis.

Objective To explore the application of three-dimensional imaging of the superior vena cava(SVC)with multi-slice spiral CT in the evaluation of catheter dysfunction after Cuff catheter implantation.Methods Twenty patients who underwent double lumen Cuff catheter indwelling for chronic renal failure at the No.971 Hospital of PLA Navy from May 2019 to August 2021,had postoperative catheter dysfunction and underwent CT three-dimensional imaging of SVC were analyzed retrospectively.Thirteen patients underwent carotid duplex ultrasound and 7 patients underwent digital subtraction angiography(DSA).The results of CT three-dimensional imaging of SVC,carotid duplex ultrasound and DSA were compared and analyzed.Results CT images clearly showed the position of the catheter implanted into different blood vessels and the location of the catheter tip in the 20 patients.There were 15 cases of dysfunction caused by peripheral thrombus,2 cases of catheter lippage,2 cases of subcutaneous tunnel pain and 1 case of no obvious symptoms after Cuff catheter implantation.Among the 13 patients undergoing carotid duplex ultrasound,thrombosis was found in the upper segment of brachiocephalic veins in one patient,dilatation or slightly smaller diameter of cervical vein or only small blood flow in 5 patients,and no abnormality in the remaining 7 patients.In the 7 patients with DSA examination,DSA was used to analyze the causes of the decrease of blood flow of long-term hemodialysis catheter and the hand swelling after fistulization,the catheter reimplantation under the guidance of DSA and the removal of fiber sheath of long-term hemodialysis catheter.Conclusion The improved CT three-dimensional imaging technique of SVC has high spatial resolution and strong repeatability,and can stereoscopically and intuitively display the position of Cuff catheter implanted into blood vessels,the location of catheter tip and thrombosis in hemodialysis patients.Carotid duplex ultrasound is only used for rough evaluation.DSA is an invasive examination and is more inclined to clinical treatment.CT three-dimensional imaging of SVC has great advantages in sensitivity,specificity and scope of examination,and it is the first choice to evaluate the causes of catheter dysfunction after Cuff catheter implantation.

Objective To explore the key points of forensics appraisal of medical disputes in mental hospitals,strengthen the management of mental hospitals,prevent medical disputes and improve medical quality.Methods Using the written judgment of China Judgments Online as materials,the order multi-class Logistic regression analysis was conducted on the common faults and level of responsibility in cases of death resulting from mental hospital treatment.Results Improper nursing,improper management,insufficient knowledge of the disease,unclear information,inadequate rescue,improper medication,unclear diagnosis were the risk factors of the degree of responsibility of medical disputes,and other diseases were protective factors.Conclusion Analyzing the common faults and identification points of death disputes in mental hospitals and rectifying them from two aspects can effectively prevent the occurrence of medical disputes,improve the quality of medical treatment,and achieve a win-win situation for doctors and patients.