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 explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation.Methods:Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization.Results:ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions:This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

AIM:This study aimed to investigate the effects of sinomenine hydrochloride(SIN)on the ultra-structure of renal tissue and the expression of interferon gene-stimulating factor in db/db mice.METHODS:Sixteen 12-week-old male db/db mice were randomly divided into two groups:a model group and a sinomenine hydrochloride(SIN)group,each consisting of 8 mice.An additional 8 wild-type(WT)mice served as the normal control group.The sinome-nine hydrochloride group was administered the treatment for 8 weeks,followed by a 20-week observation period,while the normal and model groups received an equal volume of saline via gavage.Weekly measurements were taken for body weight and fasting blood glucose.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed,and 24-hour uri-nary microalbumin(ALB)levels,as well as serum inflammatory cytokines interleukin-1β(IL-1β),IL-6 and tumor necro-sis factor-α(TNF-α),were determined using ELISA.Pathological changes in renal tissue were evaluated through hema-toxylin-eosin(HE)staining,while ultrastructural alterations were examined using transmission electron microscopy.Im-munohistochemistry and Western blotting were employed to assess STING protein expression in renal tissue,and STING mRNA expression was quantified via RT-qPCR.RESULTS:Compared to the normal group,the model group exhibited significant increases in BUN,ALB,and SCr levels(P<0.01),alongside elevated inflammatory markers IL-1β,IL-6,and TNF-α(P<0.01).Notable pathological changes included leukocyte wall thickening in capillaries,inflammatory cell infiltration,increased mesangial matrix,disorganized and linear alignment of podocytes,and thickening of the basement membrane.Moreover,STING protein and mRNA expression levels were significantly elevated(P<0.01).In contrast,the sinomenine hydrochloride group demonstrated significantly reduced levels of renal function markers(BUN,ALB and SCr)compared to the model group(P<0.01),as well as decreased concentrations of inflammatory factors IL-1β,IL-6,and TNF-α(P<0.01).Improvements in renal histopathology included decreased leukocyte wall thickening,reduced inflam-matory cell presence,diminished mesangial matrix,and a significant reduction in foot process fusion,alongside thinner basement membranes.Both STING protein and mRNA expression levels were also significantly lower(P<0.01).CON-CLUSION:Sinomenine hydrochloride effectively mitigates renal tissue injury,improves ultrastructural alterations,and inhibits inflammatory responses in db/db mice.Its mechanism of action appears closely linked to the downregulation of STING protein and mRNA expression.

[Abstrca t] Objective BRCA 1 ( breast cancer susceptibility gene 1) and RAP80 ( receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes .A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm.Patients in the control arm received docetaxel/cisplatin; in the experimental arm , patients with low RAP 80 expression received gemcitabine/cisplatin ( Arm 1 ) , those with intermediate/high RAP 80 expression and low/intermediate BRCA 1expression received docetaxel/cisplatin ( Arm 2 ) , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3).The primary end point was progression-free survival (PFS).Results 226 patients were screened and 124 were randomized in this trial.ORR in the four subgroups was 22.6%, 48.4%, 30.3%and 19.2%, respectively (P=0.08);PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84).The common adverse effects included neutropenia , nausea, anemia and fatigue.Conclusions No statistically significant difference of ORR , PFS or OS is observed in the experimental arms compared with the control arm .Patients with low RAP 80 mRNA levels have a trend of better survival and higher response rate to gemcitabine /cisplatin chemotherapy .

[Abstrca t] Objective BRCA 1 ( breast cancer susceptibility gene 1) and RAP80 ( receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes .A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression.Methods Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm.Patients in the control arm received docetaxel/cisplatin; in the experimental arm , patients with low RAP 80 expression received gemcitabine/cisplatin ( Arm 1 ) , those with intermediate/high RAP 80 expression and low/intermediate BRCA 1expression received docetaxel/cisplatin ( Arm 2 ) , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3).The primary end point was progression-free survival (PFS).Results 226 patients were screened and 124 were randomized in this trial.ORR in the four subgroups was 22.6%, 48.4%, 30.3%and 19.2%, respectively (P=0.08);PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84).The common adverse effects included neutropenia , nausea, anemia and fatigue.Conclusions No statistically significant difference of ORR , PFS or OS is observed in the experimental arms compared with the control arm .Patients with low RAP 80 mRNA levels have a trend of better survival and higher response rate to gemcitabine /cisplatin chemotherapy .

Objective To summarize our results and experience in dealing with the postoperative intrathoracic gastro-air-way fistulae after esophagectomy for esophageal carcinoma.Methods From January 2010 through February 2012,1490 patients with esophageal carcinoma underwent esophagectomy in our department.The postoperative intrathoracic gastro-airway fistulae were documented in 10 patients,with a frequency of 0.67％.Five of them died.The possible etiology,clinical characters,treatment and prevention of this complication were reviewed.Results The location of the fistulate were 7 at left main bronchus,1 at right main bronchus,and 2 at distal trachea.After 2-3 weeks conservative treatment,1 patient underwent primary surgical repair and cured,1 refused any further intervention and sacrified,8 patients underwent endoscopic insertion of covered stent and only 3 healed.For the remaining 5 cases with failed stent therapy,2 died of severe aspiration and lung infection,3 had surgical repair,one of them successed and 2 died of aspiration and aortic rupture,respecively.Conclusion The development of intrathoracic gastro-airway fistulae was associated with the iatrogenic injuries and suturing material irritation of the gastric tube to the tracheal/bronchial wall.Therefore,a meticulous closure and wapping of gastroplasty and appropriate isolation using artifical patch or great omentum between airway and esophageal substitution could effectively reduce the fistulae.The stent therapy usually fails in treating this entity and surgical repair remains the final and ratical therapeutic option.Primary repaire is suggested and careful preoperative assessment is crucial.

Objective To summarize the characteristics of ecthyma gangrenosum and explore its significance in early diagnosis of pseudomonas aeruginosa sepsis in children.Methods We retrospectively reviewed the medical records of 11 children with ecthyma gangrenosum who were hospitalized at Guangzhou women and children's medical center between May 2008 and Apr 2011.Results Eight cases were male and 7 were less than twelve months,the oldest was 2 years old,all of them were diagnosed as Pseudomonas aeruginosa spesis.Two patients had a single lesion,and the others had multiple lesions.Ecthyma gangrenosum located on the trunks in 7 cases,on anogenital areas in 5 cases,on extremities in 5 cases and on faces in 3.The lesions appeared on day 2 to day 10.On average,they developed on day 5.Seven patients developed ecthyma gangrenosum before admission,the course of the illness before admission was 6 days.Fever and multiple organ dysfunction occurred in all the patients and their cultures grew pseudomonas aeruginosa,blood cultures were positive in 8 cases,the others were isolated psudomonas aeruginosa from tissue of the lesion,discharge,ascites,pleural effusion,respectively.The time of ecthyma gangrenosum appeared was earlier than the time of the culture results reported.All of the patients were started empiric antibiotics therapy on admission,the initial antibiotic regimen was appropriate in 9 patients,8 needed surgical intervention,4 were treated with continuous blood purification.Ten patients survived and 2 died,the hospital stay was from 1 to 63 days,the average was 30.Conclusion Ecthyma gangrenosum is a known cutaneous manifestation of pseudomonas aeruginosa sepsis,which is helpful for early diagnosis and treatment,and then the outcome will be improved.