1.Research Tackling Paradigm and Technological Layout Strategies Based on Erectile Dysfunction, A Clinical Dominant Disease of Traditional Chinese Medicine
Qi ZHAO ; Yun CHEN ; Baoxing LIU ; Xuejun SHANG ; Fei SUN ; Xiaozhi ZHAO ; Zhigang WU ; Chao SUN ; Peihai ZHANG ; Wanjun CHENG ; Xing ZHOU ; Zhan QIN ; Yufeng PAN ; Weiwei TAO ; Jianhuai CHEN ; Mei MO ; Xiaoxiao ZHANG ; Xing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):291-299
To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine,the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13,2024,the 36th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing,focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction (ED). The conference brought together leading experts from traditional Chinese medicine,western medicine,and interdisciplinary fields,facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED,researching and developing new drugs of traditional Chinese medicine,and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs,it identified key directions for future scientific layout and scientific research tackling: (1) Standardization of syndrome differentiation system of traditional Chinese medicine for ED. (2) Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. (3) High-quality clinical research guided by evidence-based medicine. (4) In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. (5) Clinical translation and application promotion of new drugs of traditional Chinese medicine. (6) Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction,key focus areas,expected objectives,and clinical value were further refined,along with the establishment of a scientifically sound priority funding level evaluation system. Therefore,building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine,this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management,effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout, research and development decision-making in new drugs of traditional Chinese medicine,research topic planning,and clinical guideline formulation.
2.Regulatory Mechanism of Extracellular Vesicles in The Tumor Immune Microenvironment and Its Application in Diagnosis and Treatment
Zi-Qi WANG ; Jing WANG ; Yuan-Yu HUANG ; Mei LU
Progress in Biochemistry and Biophysics 2026;53(4):968-981
Extracellular vesicles (EVs) are pivotal mediators of intercellular communication within the tumor immune microenvironment (TME). They are broadly categorized into exosomes, microvesicles, and apoptotic bodies based on their distinct biogenesis pathways. Exosomes originate from the endosomal system via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF‑β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)‑compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.
3.Guidelines for standardized implementation of pharmacist-managed clinics (2026 edition)
Pengxiang ZHOU ; Maobai LIU ; Xiaoli DU ; Xiaoyang LU ; Mei DONG ; Rong DUAN ; Ruigang HOU ; Xiaoyu LI ; Qi CHEN ; Yanxiao XIANG ; Weiyi FENG ; Rong CHEN ; Deshi DONG ; Yong YANG ; Li LI ; Xiaocong ZUO ; Jinfang HU ; Hongliang ZHANG ; Qingchun ZHAO ; Qi LIN ; Yang HU ; Jiaying WU ; Rongsheng ZHAO
China Pharmacy 2026;37(9):1105-1112
OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics ( 2026 edition ) in response to the challenges faced by such clinics in China, including uneven development, large discrepancies in service specifications, insufficient patient awareness, and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association, the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association, a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research, current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections: definition and connotation of pharmacist-managed clinics, establishment requirements, implementation and management, post competency, and practical research. Firstly, the definition and connotation included three operational forms of pharmacist-managed clinics (independent mode, physician-pharmacist joint mode, and online pharmacist-managed clinic mode) and classified service modes (specialty-specific, drug-specific, and disease-specific pharmacist-managed clinics). The establishment requirements were further refined, covering system construction (pharmaceutical service management system, quality control and assessment mechanism), personnel qualifications (professional credentials, continuing education and professional training, etc), service recipients, as well as service venues and facilities. Subsequently, the implementation and management of pharmacist-managed clinics were proposed, involving service procedures, intervention measures, documentation and records, patient education and follow-up, humanistic care, as well as risk management and quality control. Finally, post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics, as well as the suggestions on teaching methods; practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment, management, teaching, and research, fill the guideline gap in this field, and can promote the high-quality development of pharmacist-managed clinics.
4.Resistance of Aedes albopictus to common insecticides in Zhejiang Province, 2024
Qin-mei LIU ; Jin-na WANG ; Tian-qi LI ; Ming-yu LUO ; Zhou GUAN ; Zhen-yu GONG ; Ji-min SUN
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):96-100
Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.
5.Regulatory mechanism of telomere in metabolic associated fatty liver disease and related targeted therapies
Yiming ZHAO ; Xiaomei WU ; Jing HUANG ; Qi ZHAO ; Mei YANG
Journal of Clinical Hepatology 2026;42(6):1411-1418
Metabolic associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, and its progression is closely associated with the development of liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma. However, there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes, and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD, including its molecular functions in nucleotide metabolism, oxidative stress, and epigenetic regulation, as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition, this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD, in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.
6.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
7.Clinical Randomized Controlled Trial of Traditional Chinese Medicine Compound Shenlong Decoction Granules in Treatment of Idiopathic Pulmonary Fibrosis
Qi SI ; Ningzi ZANG ; Mei WANG ; Weidong ZHENG ; Chuang LIU ; Yongming LIU ; Haoyang ZHANG ; Zhongxue ZHAO ; Jiyu ZOU ; Jingze LI ; Lijian PANG ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):237-245
ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis (IPF). MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation (30 patients) and control groups (30 patients). All patients underwent standard Western medical therapy. Additionally,the observation group received Shenlong decoction granules,while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each,taken twice daily for three months. The indexes of the patients during the treatment cycle were observed,and the main indexes include traditional Chinese medicine (TCM) syndrome scores and 6 min walk test (6MWT). The secondary indexes include pulmonary function test [actual value/expected value of total lung volume (TLC%),actual value/expected value of vital capacity(FVC%),actual/predicted diffusing capacity of the lung for carbon monoxide(DLCO%),actual/predicted forced expiratory volume in one second (FEV1%),and FEV1/ forced vital capacity (FVC)],blood gas analysis [arterial blood diathesis partial pressure of oxygen (PaO2),partial pressure of carbon dioxide (PaCO2),and arterial oxygen saturation (SaO2)],serum inflammatory factors [transforming growth factor-β1 (TGF-β1),interleukin-4 (IL-4),interleukin-13 (IL-13),interleukin-12 (IL-12),and gamma-interferon (IFN-γ)],and quality of survival evaluation [St George's Respiratory Questionnaire (SGRQ) score]. The patients' clinical manifestations were determined at the end of the treatment, and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study,comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period,the control group achieved a total effective rate of 33.33% (9/27),whereas the observation group demonstrated a total effective rate of 53.85% (14/26),which was statistically superior to the control group (χ2=4.034,P<0.05). After the treatment,the TCM syndrome scores,6MWT,DLCO%,FEV1%,PaO2,PaCO2,TGF-β1,IL-4,IL-13,IL-12,and IFN-γ in the two groups were all significantly improved (P<0.01). Compared with those in the control group after treatment at the same period,the TCM syndrome scores,6MWT,PaO2,and PaCO2 were significantly improved in the observation group after 60 days and 90 days of medication (P<0.01). Three months after the end of medication,the SGRQ score in the observation group showed significant improvement when compared to that in the control group (P<0.05),and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF,enhance exercise tolerance,improve the quality of life,and have certain potential advantages in improving pulmonary function.
8.Global burden of non-communicable diseases attributable to kidney dysfunction with projection into 2040.
Jing CHEN ; Chunyang LI ; Ci Li Nong BU ; Yujiao WANG ; Mei QI ; Ping FU ; Xiaoxi ZENG
Chinese Medical Journal 2025;138(11):1334-1344
BACKGROUND:
Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends.
METHODS:
Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040.
RESULTS:
Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively.
CONCLUSION
NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans
;
Noncommunicable Diseases/epidemiology*
;
Global Burden of Disease
;
Disability-Adjusted Life Years
;
Male
;
Female
;
Risk Factors
;
Middle Aged
;
Kidney Diseases/epidemiology*
;
Bayes Theorem
;
Adult
;
Aged
;
Global Health
;
Quality-Adjusted Life Years
9.Disulfiram alleviates cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Wei-Dong LI ; Xuan-Yang SHEN ; Xiao-Lu JIANG ; Hong-Fu WEN ; Yuan SHEN ; Mei-Qi ZHANG ; Wen-Tao TAN
Acta Physiologica Sinica 2025;77(2):222-230
The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals
;
MAP Kinase Kinase Kinases/physiology*
;
Rats
;
Myocytes, Cardiac/pathology*
;
Disulfiram/pharmacology*
;
Cardiomegaly
;
Apoptosis/drug effects*
;
Cell Line
;
Angiotensin II
;
Necroptosis/drug effects*
;
Interleukin-1beta/metabolism*
;
Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
;
Lactones
;
Resorcinols
;
Zearalenone/administration & dosage*
10.Conserved translational control in cardiac hypertrophy revealed by ribosome profiling.
Bao-Sen WANG ; Jian LYU ; Hong-Chao ZHAN ; Yu FANG ; Qiu-Xiao GUO ; Jun-Mei WANG ; Jia-Jie LI ; An-Qi XU ; Xiao MA ; Ning-Ning GUO ; Hong LI ; Zhi-Hua WANG
Acta Physiologica Sinica 2025;77(5):757-774
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
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Humans
;
Cardiomegaly/physiopathology*
;
Ribosomes/physiology*
;
Protein Biosynthesis/physiology*
;
Mice
;
Cardiomyopathy, Dilated/genetics*
;
Ribosome Profiling


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