Objective To systematically review the efficacy and safety of dapagliflozin combined with sacubitril valsartan in the treatment of heart failure after acute myocardial infarction.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on dapagliflozin combined with sacubitril valsartan(combination treatment group)vs.sacubitril valsartan(monotherapy group)for the treatment of heart failure after acute myocardial infarction from inception to June 18,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.4 software.Results A total of 11 RCTs involving 1 060 patients were included.Meta-analysis results showed that compared with the monotherapy group,the efficiency of clinical treatment(OR=5.08,95％CI 2.81 to 9.16,P＜0.001),left ventricular ejection fraction(MD=5.02,95％CI 4.08 to 5.95,P＜0.001),6-minute walking distance(MD=56.45,95％CI 32.83 to 80.07,P＜0.001)significantly increased in the combination treatment group,and the levels of N-terminal brain natriuretic peptide precursor(MD=-249.28,95％CI-414.78 to-83.78,P=0.003)and the incidence of major adverse cardiovascular events(OR=0.24,95％CI 0.15 to 0.41,P＜0.001)significantly decreased in the combination treatment group.However,there was no statistically significant difference between the two groups in terms of reducing the incidence of adverse effects(OR=0.66,95％CI 0.31 to 1.38,P=0.27).Conclusion Current evidence shows that the use of the combination of dapagliflozin and sacubitril valsartan for heart failure after acute myocardial infarction is more effective clinically and does not increase the incidence of adverse drug reactions compared with the treatment of sacubitril valsartan alone.Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

Objective:To explore the clinical feasibility of extra-peritoneal laparoscopic radical cystectomy based on the concept of 3D membrane anatomy.Methods:The clinical data of 10 male patients with bladder cancer who underwent 3D extra-peritoneal laparoscopic radical cystectomy + ileal-orthotopic-neobladder surgery from October 2020 to June 2021 were retrospectively analyzed. The median age was 67 years. The ASA score was 1-2 in 8 cases and 3 in 2 cases. There were 4 cases of hypertension, 2 cases of diabetes, 1 case of heart disease, no case of abdominal surgery history. During the operation, the concept of 3D membrane anatomy was used to identify the important fascia in the pelvic cavity and to find the key layers and structures in the pelvic cavity.It was separated from the prevesical fascia to the laterovesical space, and confluenced with Retzius space and Bogros space. It was dissected in the layer surrounded by the prevesical fascia, the vesicohypogastric fascia, and the urogenital fascia to complete the process of cystectomy.Results:The operations of 10 patients were completed successfully and there was no conversion to open operation. The median operation time was 276(237-325) minutes, and the median blood loss was 160(50-280)ml. The postoperative bowel recovery median time was 1.8(1-3)days, and the patients were out of bed about 1.3(1-2) days. The median postoperative hospital stay was 9(5-12) days. The number of median lymph node dissection in all patients was 10(6-20). Positive lymph nodes was found in 3 cases. Positive margin was found in no case. Postoperative tumor pathological stages were T 2 stage in 7 cases, T 3 stage in 3 cases. During the follow-up, all patients had no obvious complications. Conclusions:It is feasible to apply the concept of 3D membrane anatomy to identify and locate the key fascia structures and levels in extra-peritoneal laparoscopic radical cystectomy. The operative complications were less and the postoperative recovery was faster. The anatomy is clear during the operation, which has good safety and reduces the difficulty of the operation.

Objective: To evaluate the pathogenicity of Acinetobacter venetum（Av），which is expected to be used as an environmental remediation agent，using Caenorhabditis elegans（C.elegans）. Methods: The C.elegans were cultured on the media loaded with E.coli OP50 and Av，respectively. The pathogenicity of Av was evaluated by observing the effects of Av on the growth，movement，digestive function，lifespan and reproduction of C.elegans，compared with that of another evaluation system according to NY 1109-2017 General Biosafety Standard for Microbial Fertilizers. Results: By C. elegans system，it was found that the body length，width，head thrash frequency，body bending frequency and average lifespan [（13.5±0.4）d vs.（13.7±0.4）d] of adult nematodes in the Av group were not significantly different from those in the OP50 group（all P>0.05）；while the average time of defecation cycle in the Av group shortened，the total number of progenies in the Av group increased by 18.7%（all P<0.05）. According to NY1109-2017 General Biosafety Standard for Microbial Fertilizers，it was found that the oral LD50 values for both male and female mice were more than 10 g/kgbw，which was practically non-toxic；the pathogenicity test of acute intraperitoneal injection showed that the animals did not have signs of poisoning，deaths or any abnormalities in gross anatomy；Av had no irritation to damaged skin and eyes of rabbits；the hemolysis test was negative；Av was sensitive to seven antibiotics and was medium to one antibiotic. Conclusion Av is not pathogenic. C. elegans can be used in early screening for the pathogenicity of environmental remediation agents.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*