A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective:To analyze the effects of enteral nutrition on interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),pulmonary surfactant protein A(SPA),and clinical pulmonary infection score(CPIS)in patients with hospital-acquired pneumonia(HAP)after stroke.Methods:A retrospective review was conducted of the clinical records of 90 patients with hospital-acquired pneumonia following stroke admitted to the Geriatric Medicine Department of Nanjing Brain Hospital between January 2022 and February 2023.Participants were divided into a control group and a study group based on the use of enteral nutrition,with 45 patients in each group.The control group received standard treatment(conventional stroke management combined with meropenem for infection control),while the study group received standard treatment supplemented with enteral nutrition.Within the study group,cases were classified as non-severe(n=33)and severe(n=12)based on disease severity.Peripheral blood levels of IL-6,TNF-α,and SPA,alongside the Clinical Pulmonary Infection Score(CPIS),were collected.Results:Before treatment,baseline data between the study group and control group showed no statistically significant differences,with no significant differences in IL-6,TNF-α,SPA,or CPIS scores between groups(P>0.05).Following enteral nutrition therapy,the study group exhibited significantly lower levels of IL-6,TNF-α,and SPA,as well as lower CPIS scores compared to the control group,with statistically significant differences(P<0.05).Before treatment,statistically significant differences existed between severe and non-severe cases within the study group for IL-6,TNF-α,SPA,and CPIS scores(P<0.05).After therapy,no statistically significant differences were observed between non-severe and severe patients in the study group for IL-6,TNF-α,SPA levels,or CPIS scores(P>0.05).Patients in the study group demonstrated shorter symptom resolution times,overall hospital stays,and recovery times for IL-6,TNF-α,and SPA levels compared to the control group,with all differences being statistically significant(P<0.05).Conclusion:Enteral nutrition significantly reduces peripheral blood levels of IL-6,TNF-α,and SPA in patients with post-stroke HAP,lowers CPIS scores,shortens symptom resolution time and overall hospital stay,and accelerates recovery of IL-6,TNF-α,and SPA levels.

Objective To compare the application effects of plankton multiplex polymerase chain reac-tion-capillary electrophoresis(PCR-CE),SYBR Green Ⅰ real-time quantitative PCR(qPCR)and microwave digestion-vacuum filtration-automated scanning electron microscopy(MD-VF-Auto SEM)in the diagnosis of drowning.Methods Lung,liver and kidney tissues from 212 drowned corpses and 30 non-drowned corpses were examined respectively by the three drowning-related plankton testing methods,and the detection rates of plankton in each tissue by three methods were compared.Results In drowned corpses,the total detection rates of PCR-CE,qPCR,and MD-VF-Auto SEM were 93.9%,96.2%,and 95.3%,respectively,with no statistically significant difference(P>0.05).The detection rate of lung tissue by MD-VF-Auto SEM(100%)was higher than those of PCR-CE and qPCR(P<0.05),and there was no significant difference in the detection rates of the three methods in liver or kidney tissues(P>0.05).In non-drowning corpses,a small number of diatoms(less than 10 cells/10 g)were detected by MD-VF-Auto SEM method,only in liver and kidney tissues,while the other two methods yielded negative results for all tissues.Conclusion All three methods have good efficacy in the examination of drowned corpses.The MD-VF-Auto SEM method directly observes diatom morpho-logical characteristics through scanning electron microscopy,and the qualitative and quantitative analy-ses are intuitive and accurate.It has great advantages in the examination of difficult degradation samples.The PCR-CE method and qPCR method have a low sample demand(0.5 g),are easy to operate and have short detection time(4-7 h).They are easy to be applied in the grassroots depart-ments and are suitable for the rapid determination of drowned corpses in routin cases.The combina-tion of the two DNA methods with the MD-VF-Auto SEM method can increase the detection rate of plankton,ensuring the reliability of examination results.This combined use is of significant importance in the application of drowning diagnosis.

Objective: To analyze the safety and effectiveness of different types of stents with the treatment of vertebraebasilar artery dissection aneurysms(VBADA). Methods : The clinical data of 80 patients with VBADA treated by intravascular intervention in the First Hospital of University of Science and Technology of China(Anhui Provincial Hospital) from February 2018 to November 2023 were retrospectively analyzed. Patients were divided into laser engraved stent group(n=34) and braided stent group(n=46) based on the type of stent used. O′Kelly-Marotta(OKM) grade was used to evaluate the embolization effect of aneurysms in DSA images, and a modified Rankin Scale(mRS) score was used to evaluate the clinical prognosis of patients. The baseline data, aneurysm characteristics, intraoperative and perioperative treatment details and postoperative follow-up details between the two groups were compared. Results : There was no significant difference in baseline data, mRS score, ischemic and hemorrhage complications and mortality between the two groups(allP>0.05). Compared with the laser engraved stent group, the mean diameter of aneurysms was larger(P<0.000 1) and the proportion of ruptured aneurysm(P<0.01), parent artery stenosis and beaded vascular lesions(P<0.05) and branch artery dissecting aneurysm were higher(P<0.01) in the braided stent group. Conversely, the proportion of coil-assisted embolization(P<0.000 1) and the immediate aneurysm occlusion rate(OKM C and D)(P<0.000 1) were lower. Finally, 21 patients were obtained by controlling for maximum diameter of aneurysms and whether coil-assisted embolization, the aneurysm occlusion rate half a year later in the braided stent group was higher than that in the laser engraved stent group(P<0.05), but the recurrence rate of postoperative aneurysm was lower than that of laser engraved stent group(P<0.05). It was worth noting that the cure rate and vascular remodeling rate of middle-large size VBADA which the maximum diameter being over 15 mm in the braided stent group reached 72.2%, and the whole effect was ideal. Conclusion Braided stents are relatively safe and effective in the treatment of VBADA and are significantly better than laser engraved stents in reducing VBADA recurrence and remodeling lesion vessels without increasing postoperative complication.

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Objective:To evaluate trauma repair and reconstruction surgery mediated by near-infrared-Ⅱ (NIR-Ⅱ) imaging in practice of enhanced recovery after surgery (ERAS) principles.Methods:A retrospective study was conducted to analyze the data of 38 patients who had undergone trauma repair and reconstruction surgery mediated by near-infrared-Ⅱ (NIR-Ⅱ) imaging in practice of ERAS principles at Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital from May 2021 to December 2021. There were 22 males and 16 females with an age of (50.3±2.7) years. To implement ERAS, NIR-Ⅱ imaging was used for patency evaluation after vascular anastomosis in 14 cases, for skin flap harvesting and perfusion monitoring in 13 cases, and for evaluation of arterial/venous blood supply after finger replantation in 11 cases. Visual analogue scale (VAS) pain scores at 2, 7 and 14 days after surgery, length of hospital stay, patient satisfaction [by Chinese Hospital Patient Experience and Satisfaction Monitor (CHPESM)], limb function recovery (by Likert scale) and postoperative complications were recorded.Results:All patients were followed up for more than 14 days. All surgeries succeeded. The reconstructed limbs or flaps survived to recover basically normal shape and function. The VAS scores for all patients were (2.1±0.6) points, (1.6±0.6) points and (0.8±0.4) points on postoperative 2, 7 and 14 days, respectively. The length of hospital stay was (9.8±3.4) days, and the patient satisfaction was >95% at discharge. As for the recovery of limb function at the last follow-up evaluated by the Likert 5-point scale, 12 cases experienced no stiffness, 8 ones mild stiffness, 11 ones slightly severe stiffness, 3 ones moderate to severe stiffness, 2 ones severe stiffness, and 2 ones complete stiffness. Complications related to the surgery occurred in none of the patients.Conclusion:In practice of ERAS principles, application of NIR-Ⅱ imaging in trauma repair and reconstruction surgery can effectively alleviate pain, improve satisfaction, reduce hospital stay, and accelerate functional recovery for the patients.

Objective The aim of this study was to compare the effect of injection of indocyanine green(ICG)through peripheral vein and gallbladder in laparoscopic cholecystectomy(LC)of difficult gallbladder.Methods Patients with difficult gallbladder who underwent LC by the same surgical team from May to October 2023 in the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Anhui University of Science and Technology were divided into three groups according to A random number table.Group A was injected ICG through peripheral vein before operation,group B was injected ICG through gallbladder during operation,and group C was the control group.The differences of operation time,intraoperative blood loss,hospitalization time,hospitalization cost and postoperative complications among the three groups were compared,and the effects of fluorescence mode cholangio-gram in group A and group B were compared.One-way analysis of variance was used to compare the normal distri-bution of the measurement data among groups,and LSD-t test was used to compare the two groups.The counting data was compared by chi-square test.The Boferroni test was appied to compare the two groups.Results There were no differences in length of stay,hospitalization cost and postoperative complications among the three groups(P＞0.05).The operative time and intraoperative blood loss of group A and group B were lower than those of group C(P＜0.05),but there was no difference between group A and group B(P＞0.05).The total imaging rate of the first three tubes of free gallbladder triangle(early stage)in group A was 41.67%,which was significantly lower than that in group B(63.89%)(P＜0.05).Conclusion ICG is beneficial for the identification of extrahepatic bile duct structures during LC of difficult gallbladder,and ICG injection through the gallbladder is helpful for the early identification of extrahepatic bile duct.