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

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/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.

Objective To analyze the usage of pediatric drugs in 17 pediatric specialty hospitals from 2016 to 2020, and provide reference and guidance for the development of the essential medicine list （EML） for children and the improvement of the National Reimbursement Drug List （NRDL） in China. Methods Based on the pediatric medication monitoring data from 17 children's specialized hospitals reported to the Chinese Medical Economic Information Network (CMEI) of the Chinese Pharmaceutical Association between 2016 and 2020, this study analyzes the overall situation of the sample hospitals and the clinical use of pediatric drugs according to the major categories of the Anatomical Therapeutic Chemical Classification System （ATC）. Results In the various ATC categories, the trend of systemic use of anti-infective drugs decreasing was significant in the average hospital expenditure, while the trend of respiratory and digestive system and metabolic drugs decreasing was significant in the average hospital DDDS. In 2020, the average number of hospital grade standards for essential drugs （2018 version） accounted for 15.82% of the total number of drug use standards, while the average number of hospital grade standards for medical insurance （2019 version） accounted for 8.23% of the total number of drug use standards. Conclusion The use of pediatric medication in sample hospitals from 2016 to 2020 was generally reasonable, and there would still a certain gap between the actual clinical usage habits with the existing EML and NRDL，which still need to be adjusted.

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.

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.

By reviewing the ancient and modern literature， the name， origin， scientific name evolution， place of origin， quality， harvesting， processing， efficacy and toxicity of Asteris Radix et Rhizoma（ARR） were systematically sorted out， so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research， ARR was first contained in Shennong Bencaojing， all generations are Ziwan for its proper name， and there are still aliases such as Ziyuan， Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus， and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome， but in modern times， the rhizome is mostly used for propagation and cultivation， so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian（Hubei）， Zhengding and Handan（Heibei）， then the range of production areas gradually expanded， the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei， Jiangsu， Anhui， Henan and other places， since modern times， two major producing areas have been formed in Anguo， Hebei province and Bozhou， Anhui province. From the quality evaluation， it is clear that from ancient times， flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March， and then dried in the shade， and the modern harvesting is mostly in spring and autumn， and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same， mainly honey processing， there are still methods of frying， steaming， vinegar sizzling， etc. Based on the results， it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas， and those whose original formulas specify the processing requirements can be processed according to the relevant requirements， while whose processing requirements are not specified should be used in the form of raw products.

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.

OBJECTIVE To investigate the effects of brusatol on the malignant biological behavior of ovarian cancer cells by regulating the sphingosine kinase 1 （SPHK1）/sphingosine-1-phosphate （S1P）/sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway. METHODS Human ovarian cancer cell strain SKOV-3 were randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， brusatol+SPHK1 overexpression group. The cell viability， colony formation rate， the number of migration and invasion， apoptosis rate， the expressions of cell proliferation-related proteins [myelocytomatosis viral oncogene homolog （C-myc）]， apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）]， epithelial mesenchymal transition （EMT）-related proteins （E-cadherin， N-cadherin） and SPHK1， S1P， S1PR3 proteins were all detected in each group. Transplanted tumor model of nude mice was constructed by using SKOV-3 cells and randomly separated into control group， brusatol low-dose， medium-dose and high-dose groups， SPHK1 overexpression group， high- dose brusatol+blank load group， and high-dose brusatol+SPHK1 overexpression group； the growth of transplanted tumors were detected. The nude mice model of SKOV-3 transplantation tumor was randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， and brusatol+SPHK1 overexpression group； the proliferation and apoptosis of transplanted tumor tissue， the expressions of EMT-related Δ 基金项目江西省中医药管理局科技计划项目（No.2023B0762） ＊第一作者 副主任药师 。研究方向 ：药学研究及药理学 。E- proteins and SPHK1/S1P/S1PR3 signaling pathway proteins mail：jsgj2023@126.com were detected in each group. RESULTS Cell experiments in # 通信作者 主任医师，硕士。研究方向：妇科及妇科肿瘤学。E- vitro had shown that compared with the control group， the cell mail：11638199@qq.com viability， clone formation rate， migration number， invasion 中国药房 2024年第35卷第16期 China Pharmacy 2024 Vol. 35 No. 16 · 1991 · number， protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 were decreased significantly in brusatol group （P＜0.05）， while the apoptosis rate， protein expressions of Bax and E-cadherin were increased significantly （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in SKOV-3 cells. Mice experiments in vivo had shown that compared with the control group， the transplanted tumor volumes of nude mice in the brusatol low-dose， medium- dose and high-dose groups were decreased significantly in a dose-dependent manner after 21 days of intervention （P＜0.05）. Brusatol of high dose could also significantly reduce the protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 in transplanted tumor tissue of nude mice （P＜0.05）， and significantly increase the protein expressions of Bax and E- cadherin （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in transplanted tumor tissue of nude mice. CONCLUSIONS Brusatol can inhibit the proliferation， cloning， EMT， migration and invasion of ovarian cancer cells， and induce their apoptosis by down-regulating the expression of SPHK1/S1P/S1PR3 signaling pathway. It can also inhibit the growth of ovarian cancer cells in nude mice， ultimately suppressing their malignant biological behavior and exerting significant anti-cancer effects on ovarian cancer.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.