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 evaluate the effectiveness of the channel-assisted minimally invasive repair (CAMIR) technique combined with flexor hallucis longus (FHL) tendon transfer in the treatment of Achilles tendon sleeve avulsion. METHODS: A retrospective analysis was conducted on 17 patients with Achilles tendon sleeve avulsion who underwent CAMIR technique combined with FHL transfer between January 2019 and January 2023. The cohort comprised 13 males and 4 females, aged 32 to 65 years (mean, 49.7 years). Etiologies included sports-related injuries in 15 cases and blunt trauma in 2 cases. The interval from injury to surgery ranged from 4 to 368 days (median, 15 days). All patients exhibited calcification at the Achilles tendon insertion site, with 7 cases complicated by Haglund deformity. Postoperative complications were meticulously monitored, and tendon healing was assessed via MRI. Clinical outcome were evaluated using the visual analogue scale (VAS) score for pain, Tegner activity level rating scale, ankle activity score (AAS), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Victorian Institute of Sport Assessment-Achilles (VISA-A) score, and subjective clinical scoring systems preoperatively and at last follow-up. RESULTS: The operation time was 50-62 minutes (mean, 56 minutes), and the intraoperative blood loss was 5-50 mL (mean, 19.7 mL). All patients were followed up 12-67 months (mean, 38 months). No postoperative complication, such as Achilles tendon re-rupture, incision infection, deep vein thrombosis, heel raise insufficiency, or sural nerve injury, was observed. At last follow-up, MRI examination confirmed satisfactory tendon healing in all cases. Significant improvements were noted in VAS scores, Tegner activity level rating scale, AAS scores, AOFAS ankle-hindfoot scores, and VISA-A scores compared to preoperative ones ( P<0.05). At last follow-up, the subjective clinical score ranged from 6 to 10 (median, 9). CONCLUSION The CAMIR technique combined with FHL tendon transfer is a good treatment for repair of Achilles tendon sleeve avulsion, with good recovery of ankle function and few complications.
Humans ; Achilles Tendon/diagnostic imaging* ; Middle Aged ; Male ; Female ; Tendon Transfer/methods* ; Minimally Invasive Surgical Procedures/methods* ; Adult ; Retrospective Studies ; Aged ; Treatment Outcome ; Tendon Injuries/surgery*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To compare regional pulmonary ventilation and perfusion and ventilation/perfusion(V/Q)matching in different body positions using electrical impedance tomography(EIT).Methods Ten healthy experimental pigs were selected to collect their EIT lung ventilation and perfusion data in supine,prone,left lateral and right lateral positions.The EIT data underwent analysis and image reconstruction using MATLAB R2022b and EIDORS v3.9.The effective regions with ventilation and perfusion were determined and the V/Q matching regions were computed with the maximum pixel value 20％as the threshold.Comparisons were carried out over the V/Q matching indexes including V/Q match％,dead space％and shunt％and ventilation and perfusion distribution in regions of interest(ROIs)including ROI1,ROI2,ROI3 and ROI4 in different body positions.Results The differences in V/Q match％,dead space％and shunt％of the experimental animals in varied positions were not statistically significant(P＞0.05).The regional distribution of pulmonary ventilation and perfusion changed in different positions,and the regional distributions differed in ROIl,ROI2 and ROI3 for ventilation(P＜0.05)and in ROI1 and ROI2 for perfusion(P＜0.05).The ventilation and perfusion regions were distributed consistently with the gravity-dependent areas in supine and prone positions whereas conversely in the right and left lateral positions.Conclusion The V/Q matching indexes of one subject have high test consistency in different body positions;gravity-dependent areas varied with the changes of the body positions,which affected the distribution of pulmonary ventilation and perfusion regions;EIT can be used for measuring the changed pulmonary ventilation and perfusion due to different positions and determining the influences of position changes on pulmonary ventilation and perfusion and V/Q matching.[Chinese Medical Equipment Journal,2024,45(5):1-7]

The gallium-based liquid metals were introduced in terms of the advantages when applied in medical field,application status in medical imaging,drug delivery,antibiosis and tumor therapy and cutting-edge application in flexible e-skin,wearable sensor and flexible medical device.The deficiencies of the gallium-based liquid metals in durability,potential toxicity,high cost of preparation and difficulty of process control were analyzed when applied in medical fields.The future development directions of the gallium-based liquid metals were pointed out.[Chinese Medical Equipment Journal,2024,45(11):97-102]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

ObjectiveThis study aims to explore the effect of ultrasound-guided superficial parasternal intercostal plane block on the quality of recovery and postoperative analgesia in patients undergoing sternotomy cardiac surgery. MethodsA total of 64 patients undergoing sternotomy cardiac surgery were selected for this study. They were randomly divided into two groups： one group received a superficial parasternal intercostal plane block with ropivacaine （the ropivacaine group）， while the other was given normal saline （the normal saline group）. The primary outcome was the Quality of Recovery-15 （QoR-15） score on postoperative day 1 in both groups， accompanied by a comparative analysis of the pain score and opioid usage. ResultsCompared with the normal saline group， the ropivacaine group exhibited a significantly higher QoR-15 score on postoperative day 1［（89.60±13.24） vs （81.18±12.78）， P=0.012］. The numerical rating scale at rest was significantly lower［（3.03±0.72） vs （4.26±0.93）， P<0.001］， and the numerical rating scale during coughing was also significantly reduced ［（4.40±0.89） vs （5.44±1.05）， P<0.001］. Concurrently， the cumulative morphine equivalent consumption during the initial 24 h postoperatively was significantly lower in patients who were administered the ropivacaine ［14.15 （4.95～30.00） mg vs 40.50 （19.25～68.18） mg， P=0.002］， and there was also a notable decrease in the rescue analgesia ［0.00 （0.00～0.00） mg vs 0.00 （0.00～100.00） mg， P=0.007］. ConclusionUltrasound-guided superficial parasternal intercostal plane block can significantly enhance the overall quality of recovery in patients undergoing sternotomy cardiac surgery on postoperative day 1. The technique contributes to improved postoperative analgesic effects and a reduction in opioid usage， thereby facilitating early postoperative recovery.

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.