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

This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Autophagy/drug effects* ; Rats ; Rats, Sprague-Dawley ; Interstitial Cells of Cajal/metabolism* ; Dyspepsia/physiopathology* ; Protein Serine-Threonine Kinases/genetics* ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Signaling System/drug effects* ; Humans ; Endoribonucleases/genetics* ; Multienzyme Complexes

In order to support the implementation of the Opinions on Improving the Quality of Traditional Chinese Medicine and Promoting the High-Quality Development of the Traditional Chinese Medicine Industry and fundamentally promote the high-quality development of Chinese materia medica(CMM) industry, this article analyzed the quality and safety issues arising during the transition of CMM from wild harvesting to cultivation. Root causes of these issues were identified, including changes in the habitats of medicinal plants caused by inappropriate field cultivation patterns, excessive use of chemical inputs such as fertilizers and pesticides, and shortened cultivation periods due to rising economic costs. To address the above issues, the following countermeasures and suggestions were proposed to advance the high-quality development of CMM:(1) comprehensively adjust the cultivation patterns, vigorously promote ecological cultivation of CMM, and ensure production quality and safety of CMM from the source;(2) strengthen the breeding of high-quality, stress-resistant CMM varieties, improve cultivation techniques to reduce the use of fertilizers and pesticides, and improve the quality and efficiency of ecological cultivation of CMM;(3) systematically design the production, operation, and supervision models for ecological cultivation of CMM, carry out demonstrations of "high quality with fair price", and ensure the sustainable development of ecological cultivation of CMM.
Drugs, Chinese Herbal/standards* ; Quality Control ; Plants, Medicinal/chemistry* ; Plant Roots/chemistry* ; China ; Fertilizers/analysis* ; Materia Medica/standards* ; Medicine, Chinese Traditional/standards*

This article aims to compare and analyze the biomechanical differences between wing-shaped titanium plates and traditional titanium plates in fixing acetabular anterior column and posterior hemi-transverse (ACPHT) fracture under multiple working conditions using the finite element method. Firstly, four sets of internal fixation models for acetabular ACPHT fractures were established, and the hip joint stress under standing, sitting, forward extension, and abduction conditions was calculated through analysis software. Then, the stress of screws and titanium plates, as well as the stress and displacement of the fracture end face, were analyzed. Research has found that when using wing-shaped titanium plates to fix acetabular ACPHT fractures, the peak stress of screws decreases under all working conditions, while the peak stress of wing-shaped titanium plates decreases under standing and sitting conditions and increases under forward and outward extension conditions. The relative displacement and mean stress of the fracture end face decrease under all working conditions, but the values are higher under forward and outward extension conditions. Wing-shaped titanium plates can reduce the probability of screw fatigue failure when fixing acetabular ACPHT fractures and can bear greater loads under forward and outward extension conditions, improving the mechanical stability of the pelvis. Moreover, the stress on the fracture end surface is more conducive to stimulating fracture healing and promoting bone tissue growth. However, premature forward and outward extension rehabilitation exercises should not be performed.
Titanium ; Bone Plates ; Humans ; Acetabulum/surgery* ; Fracture Fixation, Internal/methods* ; Biomechanical Phenomena ; Finite Element Analysis ; Bone Screws ; Fractures, Bone/surgery* ; Stress, Mechanical ; Working Conditions

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in adolescents, with potential causes etiologies associated with mesenchymal stem cells, genetic factors, histological features, and biomechanical aspects. Biomechanically, the pelvis, serving as the central and majort load-bearing structure, exhibits morphological and alignment abnormalities highly correlated with the development of AIS. Recent studies have extensively explored three-dimensional pelvic parameters and kinematics, demonstrating that abnormal pelvic characteristics may contribute to AIS onset and progression and are increasingly incorporated into clinical interventions. This review summarizes sagittal and coronal features of the spine-pelvis, as well as the influence of three-dimensional kinematic features on the pathogenesis of AIS, providing insights for advancing the study of spine-pelvis features related to AIS.
Humans ; Scoliosis/pathology* ; Adolescent ; Spine/pathology* ; Pelvis/pathology* ; Biomechanical Phenomena

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. METHODS: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. RESULTS: The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. CONCLUSIONS SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals ; Myocytes, Cardiac/metabolism* ; Apoptosis/drug effects* ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Doxorubicin/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Drug Combinations ; Injections ; Rats

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective:To explore the diagnostic value of ultrasonography for injuries of anterior talofibular ligament(ATFL)and anterior inferior tibiofibular ligament distal fascicle(ATiFL-DF)in patients with ankle fractures.Methods:Clinical data of 51 patients with ankle fractures who were clinically suspected of ligament injuries and underwent ankle ultrasonography examination and arthroscopy in Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from April 2019 to March 2023 were retrospectively analyzed.Using arthroscopic results as the gold standard,the sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of ultrasonography in diagnosing ATFL and ATiFL-DF injuries were evaluated,and Kappa consistency test was performed.Results:The sensitivity and specificity of ultrasonography in diagnosis of ATFL injury were 100.0%and 92.3%,with the PPV of 92.6%and NPV of 100.0%.Ultrasonography findings exhibited excellent concordance with arthroscopic results(kappa=0.849).The sensitivity and specificity of ultrasonography in diagnosis of ATiFL-DF injury was 86.7%and 33.3%,with the PPV of 90.7%and NPV of 25.0%.However,the consistency between ultrasonography and arthroscopic results was poor(kappa=0.168).Conclusions:Ultrasonography is reliable in assessing injuries of ATFL in patients with ankle fractures,but its specificity in diagnosing ATiFL-DF is poor.Therefore,ankle arthroscopy remains necessary for ankle fracture patients with negative findings of ATiFL-DF in ultrasonography.

Objective To summarize and analyze the surgical evolution and clinical efficacy of benign prostatic hyperplasia(BPH)surgery.Methods A retrospective cohort study was used to analyze the clinical data of 2050 patients who underwent surgery for BPH in the Department of Urology,the First Medical Center of PLA General Hospital from January 2012 to August 2022.These patients were divided into 3 groups in chronological order:the early group(n=683),the middle group(n=683)and the late group(n=684).The cumulative time of patients in each group was from January 2012 to February 2017,March 2017 to September 2020 and October 2020 to August 2022.The indicators,such as age,hypertension,diabetes,serum cholesterol,serum triacylglycerol,serum high-density lipoprotein cholesterol,body mass index(BMI),preoperative prostate volume,prostate specific antigen(PSA),free prostate specific antigen(fPSA),operation time,preoperative hospital stay,postoperative hospital stay,postoperative bladder flushing time,postoperative indwelling time,cystostomy situation,intraoperative and postoperative blood transfusion,postoperative readmission rate,and postoperative pathology were collected and compared between 3 groups,and the annual trend of changes in the number of BPH surgeries and surgical methods was analyzed.Results Transurethral resection of prostate(TURP)and TURP+laser resection decreased year by year,while transurethral laser resection of prostate increased and became the mainstream prostate resection method in recent two years,accounting for more than 90%.The patients in the early,middle and late groups were(69.7±7.9)years old,(68.7±7.4)years old and(69.8±8.5)years old(P=0.027);the operation time was 108.0(80.0,130.0)min,80.0(60.0,110.0)min and 75.0(60.0,100.0)min(P<0.001);the postoperative indwelling time was 4.1(2.7,5.9)d,3.9(2.9,4.9)d and 2.7(0.9,3.9)d(P<0.001);the rates of cystostomy were 68.8%,66.6%and 5.0%(P<0.001);the intraoperative and postoperative blood transfusion rates were 4.5%,3.1%and 0.9%(P<0.001);the preoperative hospitalization time was 5.6(3.8,7.1)d,4.7(3.5,5.9)d,and 4.7(3.1,6.7)d(P<0.001);the postoperative hospital stays were 5.7(4.8,7.0)d,4.7(3.0,5.9)d and 2.8(1.0,4.0)d(P<0.001),with statistically significant differences.Thirty-seven cases(1.8%)of BPH patients who underwent surgery in our center for 10 years were re-admitted after surgery,and 64 cases had postoperative pathological abnormalities or were diagnosed with prostate cancer,with a total detection rate of 3.1%.Conclusions Laser enucleation of prostate has become the mainstream surgical treatment of BPH in our center,and perioperative indexes such as operation time,hospital stay,postoperative catheter indwelling time,cystostomy rate,and surgical blood transfusion rate have shown a significant improvement trend.