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 survey and analysis of cephalometric indicators of Wa adults in China.Methods Cephalometric parameters were measured in 1996 cases(858 males and 1138 females)of Wa adults in China,including 927 cases(381 males and 546 females)of the Baraoke ethnic group,564 cases(241 males and 323 females)of the A Wa ethnic group,and 505 cases(236 males and 269 females)of the Wa ethnic group by using sliding caliper and spreading caliper.Seventeen direct cephalofacial parameters and one indirect parameter for each of the three dialect ethnic groups were derived separately and analyzed for age correlations,inter-sex u-tests,and multiple comparisons.Finally,the three dialect ethnic groups were subjected to cluster analysis and principal component analysis with 15 ethnic groups in China.Results Nose breadth,mouth breadth and physiognomic ear length were significantly and positively correlated with age for both sexes in the three Wa dialect ethnic groups,while head breadth and lip height were significantly and negatively correlated with age.Except for the interocular breadth,there were gender differences between males and females in the cephalometric parameters of the three Wa dialect ethnic groups.The cephalofacial features of the Baraoke,A Wa and Wa ethnic groups were different,as evidenced by the fact that males and females of the Baraoke and Wa dialect ethnic group had higher lip height,wider nasal breadth and wider mouth breadth,while males and females of the A Wa ethnic group had lower nasal height.Conclusion The cephalofacial features of the three Wa dialect ethnic groups are close to those of the Khmus and Mang,who have their origins in the ancient Baipu people and are also members of the Mon-Khmer language group of the Austroasiatic linguistic.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To explore the effect of the evidence-based practice nursing program for severe patients with physical constraints based on the guideline in Intensive Care Unit (ICU) patients.Methods:From February 2019 to July 2020, 4 663 patients in the Surgical Intensive Care Unit (SICU), Medicine Intensive Care Unit (MICU), Coronary Care Unit (CCU), and Emergency Intensive Care Unit (EICU) of the China-Japan Friendship Hospital were selected as the research object by purposive sampling. The evidence-based practice nursing program for severe patients with physical constraints based on the guideline of Promoting Safety: Alternative Approaches to the Use of Restraints was applied in clinical practice. We recorded the constraint duration, constraint rate, and substitution constraint rate of severe patients after the implementation of the program, and compared the differences in ICU nurses' scores on physical constraint knowledge, attitude, and practice before and after the implementation of the program. Results:Out of 4 663 patients, 871 received restraint, with a restraint rate of 18.68% and a restraint duration of (102.35±82.67) hours. The number of substitution constraint cases was 421, and the substitution constraint rate was 9.03%. The constraint rates in SICU, MICU, CCU and EICU were 23.68% (475/2 006), 28.26% (219/775), 7.29% (97/1 331) and 14.52% (80/551), respectively, and the differences in constraint rates among different departments were statistically significant ( P<0.05). Before and after the implementation of the program, there were statistically significant differences in the scores of ICU nurses on physical constraint knowledge, attitude, and practice dimensions and total scores ( P<0.05) . Conclusions:The evidence-based practice nursing plan program for severe patients with physical constraints based the guideline effectively reduces the rate and duration of physical constraint of ICU patients, improves the substitution constraint rate, standardizes the practice of physical constraint of ICU patients, and ensures patient safety.